Electrohydraulic shock wave decalcification of stenotic aortic valves: postmortem and intraoperative studies.

Decalcification of stenotic aortic valves is limited by the difficulty in removing sufficient calcium to restore valve function without cusp perforation. The present study demonstrates that electrohydraulic shock waves generated by a hand-held lithotriptor fragmented the calcifications contained within the cusps of four necropsy specimens of stenotic aortic valves. The electrohydraulic shock waves appeared to create a cleavage plane between the valve tissue and the fragmented calcific deposits, allowing the fragmented calcified masses to be removed without cusp perforation. Five patients with severe aortic stenosis also underwent successful aortic valve decalcification augmented by electrohydraulic shock waves generated with the hand-held lithotriptor, without significant complication. The shock waves permitted removal, from the aortic valve, of calcium that had not been removed by mechanical means. These results indicate that the addition of electrohydraulic shock waves to mechanical aortic valve decalcification may facilitate successful decalcification in patients undergoing operative treatment for aortic stenosis and may allow patients to avoid the need for aortic valve replacement.

Comparison of time domain and frequency domain variables from the signal-averaged electrocardiogram: a multivariable analysis.

The relative values of the unprocessed signal-averaged electrocardiogram (ECG) and time domain analysis and frequency domain analysis of the signal-averaged ECG were compared in 36 patients with sustained monomorphic ventricular tachycardia and a remote myocardial infarction, in 29 asymptomatic patients with a remote myocardial infarction and in 23 normal subjects. Area ratios of the energy spectra derived from fast Fourier transform analysis were calculated using six separate 140 ms intervals starting at 0, 40, 50 and 60 ms after QRS onset; 40 and 50 ms before QRS end and a variable length interval starting 40 ms before QRS end and extending to the T wave. Total filtered QRS duration, late potential duration and root mean square voltage of the terminal QRS complex were measured from the filtered vector magnitude signal-averaged ECG. The total QRS duration was also measured from the X, Y, Z leads of the unfiltered signal-averaged ECG. Seven variables were significantly different in univariate tests between myocardial infarction patients with and without ventricular tachycardia: three fast Fourier transform area ratios with the sampling interval starting at 1) QRS onset (p = 0.007), 2) 40 ms after QRS onset (p = 0.02), and 3) 60 ms after QRS onset (p less than 0.0001); and all four time domain variables at 1) total filtered QRS duration (p less than 0.0001), 2) late potential duration (p = 0.0001), 3) root mean square terminal QRS voltage (p = 0.0001), and 4) QRS duration from the unprocessed signal-averaged ECG (p less than 0.0001). Of these seven variables, only the fast Fourier transform area ratio starting at QRS onset was significantly different between patients with myocardial infarction without ventricular tachycardia and normal subjects. In multi-variable analysis, the total filtered vector magnitude QRS duration, a time domain variable that includes the late potential, was the only independent factor that separated patients with myocardial infarction with and without associated ventricular tachycardia.

Accelerated plasminogen activator dose regimens for coronary thrombolysis. The TAMI-7 Study Group.

To determine the clinical profile and efficacy of accelerated recombinant tissue-type plasminogen activator (rt-PA) dose regimens, five different strategies of thrombolytic therapy in a total of 232 patients were systematically evaluated in the setting of acute myocardial infarction. The fifth strategy involved a combination of accelerated rt-PA and intravenous urokinase (regimen E). A weight-adjusted dose of 1.25 mg/kg body weight of tissue plasminogen activator over 90 min (regimen C) yielded the highest coronary patency rate (83%) at acute angiography. The associated in-hospital reocclusion rate for this regimen was low (4%). An exaggerated (60-min) dosage regimen yielded an inferior coronary patency rate (63%). Combination therapy (regimen E) was associated with a 72% patency rate and 3% reocclusion rate. Marginal improvement in global ejection fraction and regional wall function was demonstrated with all strategies by predischarge catheterization. Bleeding complications were most common at the periaccess site and were not different from those in previous experiences reported with conventional 3-h dosing regimens. Measurements of baseline, 30-min and 3-h levels of tissue plasminogen activator, fibrinogen and fibrin(ogen) degradation products were obtained. At 3 h, fibrinogen levels of less than 1 g/liter were demonstrated with combination therapy (regimen E) as well as with regimen C. Major clinical outcomes including death, reocclusion and reinfarction also showed a tendency to be less common with regimen C. Therefore, although accelerated dose regimens of rt-PA do not reliably yield acute coronary patency rates greater than 85%, an acute coronary patency rate of approximately 85% can be approached.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased risk of non-Q wave myocardial infarction after directional atherectomy is platelet dependent: evidence from the EPIC trial. Evaluation of c7E3 for the Prevention of Ischemic Complications.

OBJECTIVES: We sought to determine the effects of platelet glycoprotein IIb/IIIa receptor blockade on adverse outcomes, especially non-Q wave myocardial infarction, in patients undergoing directional atherectomy in the Evaluation of c7E3 for the Prevention of Ischemic Complications (EPIC) trial. BACKGROUND: Randomized trials comparing directional atherectomy with percutaneous transluminal coronary angioplasty (PTCA) have demonstrated modest benefits favoring atherectomy but at a cost of increased acute ischemic complications, notably non-Q wave myocardial infarction. The mechanism for this excess risk is unknown. METHODS: Of 2,038 high risk patients undergoing coronary intervention in the EPIC trial, directional atherectomy was performed in 197 (10%). Patients randomly received the chimeric glycoprotein IIb/IIIa antibody 7E3 (c7E3), as a bolus or a bolus and 12-h infusion or placebo. Study end points included death, myocardial infarction, repeat intervention or bypass surgery. RESULTS: Patients undergoing directional atherectomy had a lower baseline risk for acute complications but had a higher incidence of any myocardial infarction (10.7% vs. 6.3%, p = 0.021) and non-Q wave myocardial infarction (9.6% vs. 4.9%, p = 0.006). Bolus and infusion of c7E3 reduced non-Q wave myocardial infarctions by 71% after atherectomy (15.4% for placebo vs. 4.5% for bolus and infusion, p = 0.046). Non-Q wave myocardial infarction rates after PTCA were not affected by c7E3, although Q wave myocardial infarctions were reduced from 2.6% to 0.8% (p = 0.017). CONCLUSIONS: The EPIC trial confirmed the increased risk of non-Q wave myocardial infarction with directional atherectomy use compared with PTCA. A bolus and 12-h infusion of the glycoprotein IIb/IIIa receptor inhibitor c7E3 abolished this excess risk. Directional atherectomy-related non-Q wave myocardial infarction appears to be platelet aggregation dependent.

Mechanism of benefit of combination thrombolytic therapy for acute myocardial infarction: a quantitative angiographic and hematologic study.

OBJECTIVES: The goal of this study was to lend insight into the mechanisms responsible for the beneficial effects of combination thrombolytic therapy. BACKGROUND: Combination thrombolytic therapy for acute myocardial infarction has been associated with less reocclusion and fewer in-hospital clinical events than has monotherapy. METHODS: Infarct-related quantitative coronary dimensions and hemostatic protein levels were evaluated in 287 patients with acute myocardial infarction during the early (90-min) and convalescent (7-day) phases after administration of recombinant tissue-type plasminogen activator (rt-PA), urokinase or combination rt-PA and urokinase. RESULTS: Minimal lumen diameter was similar in the 90-min and 7-day phases after treatment with rt-PA, urokinase and combination rt-PA and urokinase (0.72 +/- 0.45 mm, 0.62 +/- 0.53 mm and 0.75 +/- 0.58 mm, respectively, at 90 min, p = 0.16; and 1.05 +/- 0.56 mm, 1.12 +/- 0.72 mm and 0.94 +/- 0.54 mm, respectively, at 7 days, p = 0.22). In-hospital clinical event and reocclusion rates were less frequent in patients receiving combination therapy than in those receiving monotherapy (25% vs. 38% and 32% for rt-PA and urokinase, respectively, p = 0.084; and 3% vs. 13% and 9% for rt-PA and urokinase, respectively, p = 0.03), but these events were unrelated to early or late coronary dimensions. Patients receiving combination therapy or urokinase monotherapy had significantly higher peak fibrin degradation products (1,307 +/- 860 and 1,285 +/- 898 micrograms/ml vs. 435 +/- 717 micrograms/ml, respectively, p < 0.0001) and lower nadir fibrinogen levels (0.85 +/- 1.00 and 0.75 +/- 0.53 g/liter vs. 1.90 +/- 0.86 g/liter, respectively, p < 0.0001) than did those receiving rt-PA monotherapy. Peak fibrinogen degradation products indirectly correlated (p = 0.004) and baseline (p = 0.026) and nadir (p = 0.089) fibrinogen levels directly correlated with reocclusion. CONCLUSIONS: Lower in-hospital clinical event and reocclusion rates observed with combination thrombolytic therapy may relate to systemic hematologic factors rather than to the residual lumen obstruction after thrombolysis.

Determinants of the need for early acute intervention in patients treated conservatively after thrombolytic therapy for acute myocardial infarction. TAMI-5 Study Group.

This study sought to determine whether clinical variables can be used to identify patients at high risk of recurrent spontaneous myocardial ischemia or hemodynamic compromise during the 1st 4 days after intravenous thrombolysis for acute myocardial infarction. Of 288 patients randomly assigned to a conservative postthrombolysis strategy, 54 (19%) required urgent cardiac catheterization within 24 h; 75 (26%) underwent urgent cardiac catheterization within 4 days of admission. Of the clinical variables examined by multiple logistic regression analysis, only patient age and anterior wall myocardial infarction correlated with the need for urgent cardiac catheterization (p = 0.0016 and p = 0.017, respectively). Compared with recombinant tissue-type plasminogen activator or urokinase monotherapy, combination therapy with these agents was associated with a lower need for acute intervention during the 1st 24 h after admission, but the difference did not reach statistical significance (14% for combination therapy vs. 21% for each agent alone, p = 0.30). Of the 75 patients undergoing urgent coronary angiography, only 39% had an occluded infarct-related artery. Emergency coronary angioplasty was performed in 49% of the patients and coronary artery bypass graft surgery was performed urgently in 3%. Despite these interventions, the need for urgent cardiac catheterization was associated with an in-hospital mortality rate of 7% (vs. 3% in the group not requiring urgent angiography, p = 0.36); mean left ventricular ejection fraction was 50.5 +/- 11% (vs. 54.3 +/- 10.8%, p = 0.12) and regional infarct zone wall motion was -2.68 +/- 1.07 SD/chord (vs. -2.46 +/- 1.19 SD/chord; p = 0.44).(ABSTRACT TRUNCATED AT 250 WORDS)

Development of an endocardial-epicardial gradient of activation rate during electrically induced, sustained ventricular fibrillation in dogs.

Electrograms recorded with currently available electrodes become indistinct soon after the onset of ventricular fibrillation (VF), thus, little is known about transmural myocardial depolarization during VF. A plunge electrode system (plunge) was developed that registers discrete deflections during VF. These plunges were used to record for 20 minutes after inducing VF with a single premature shock in 20 open-chest dogs. In the first 6 dogs the epicardium was exposed to room temperature and in 14 dogs transmural temperature was maintained at 38 degrees C. Electrograms recorded with the transmural plunges contained sharp, discrete deflections during early VF in all dogs. Over the next 20 minutes of VF, the rate, regularity of cycle length and discreteness of the deflections in the electrograms decreased with time, first at the epicardial level, then deeper toward the endocardium. In all dogs, however, discrete, regular, rapid deflections persisted in the most subendocardial electrogram throughout the recording period. In 8 dogs, transmural myocardial biopsy samples were taken before fibrillation, and at intervals after the onset of fibrillation. The high-energy phosphate content of the myocardium decreased during VF, with comparable decreases in the epicardial and endocardial halves. Coronary perfusion was maintained during the first 20 minutes of VF in 6 additional dogs by cardiopulmonary bypass. A gradient of activation rates did not develop on bypass, but did develop within 1 minute of halting bypass. Thus, the endocardial-epicardial gradient of activation rates during VF is caused by ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Transvenous ablation of the atrioventricular conduction system in dogs: electrophysiologic and histologic observations.

The correlation of histologic and electrophysiologic findings in dogs undergoing transvenous ablation of atrioventricular (AV) conduction has not been described. The creation of complete AV block in 10 dogs was attempted by delivering a direct-current shock transvenously through a standard tripolar electrode catheter. The catheter was positioned to record the largest unipolar atrial and His bundle electrograms. A 280 J shock was delivered to the recording electrode by a standard cardioversion unit. After 1 shock, all dogs were in complete AV block refractory to isoproterenol (1 to 4 micrograms/min) and atropine (0.5 to 2.0 mg). Four weeks later, 5 dogs remained in complete AV block, 1 had first-degree block, and 4 had resumed normal AV conduction. Each dog with complete heart block had histologic evidence of severe damage to the AV node, His bundle, or both. On gross examination, these dogs were found to have discrete scars at the base of the septal leaflet of the tricuspid valve. Of the 5 dogs that had resumption of AV conduction, only 1 had histologic evidence of significant damage to the AV conduction system. That animal manifested a marked increase in the P-R interval (100 to 210 ms). Although temporary heart block occurred in each animal, chronic interruption of AV conduction was more difficult. Catheter location, atrial and His bundle electrogram relations, and the electrode used for delivery of energy were factors determining the effectiveness of this technique.

Tachycardia-induced cardiomyopathy: a reversible form of left ventricular dysfunction.

Eight patients, aged 5 to 57 years, with uncontrolled symptomatic tachycardia for 2.5 to 41 years (mean 15) and significant left ventricular (LV) dysfunction in the absence of any other apparent underlying cardiac disease underwent evaluation. Incessant tachycardia was present for 0.5 to 6.0 years (mean 2.1) in 7 patients. One patient had an ectopic atrial tachycardia and 7 patients had an accessory atrioventricular pathway that participated in reciprocating tachycardia. Six patients underwent surgery; the ectopic focus was ablated in 1 patient and an accessory pathway was divided in 5 patients. One patient underwent open ablation of the His bundle and 1 patient underwent closed-chest ablation of the atrioventricular conduction system. Myocardial biopsy specimens were obtained from 5 patients, none of which yielded a specific diagnosis. Pretreatment radionuclide angiography demonstrated a mean ejection fraction (EF) of 19 +/- 9% (range 10 to 35%). Following tachycardia control a marked improvement in LV function was noted in 6 of 8 patients at rest and in 1 additional patient during exercise. The EF increased to 33 +/- 17% (range 16 to 56%) an average of 8 days after treatment and to 45 +/- 15% (range 22 to 67%) at late follow-up 3.5 +/- 40 months (mean 17) later (p less than 0.005). Seven patients remain asymptomatic 11 to 40 months (mean 22) after the corrective procedure and have resumed normal activities. These findings suggest that chronic uncontrolled tachycardia may result in significant LV dysfunction, which is reversible in some cases after control of the arrhythmia.

Frequency, significance, and cost of recurrent ischemia after thrombolytic therapy for acute myocardial infarction. TAMI Study Group.

Early postinfarction angina implies an unfavorable prognosis. Most published information on this outcome represents data collected in the prethrombolytic era, in which definitions and populations differed considerably. Our purpose was to evaluate the incidence and importance of recurrent ischemia after administration of thrombolytic therapy. We studied patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction studies. Patients were enrolled into 5 studies with similar entry criteria; 552 patients were treated with tissue plasminogen activator (t-PA), 293 were treated with urokinase, and 385 received both thrombolytic agents. Recurrent ischemia was defined as symptoms in association with electrocardiographic changes; reinfarction was defined as a reelevation of creatine kinase myocardial band isoenzyme in an appropriate clinical setting. Both recurrent ischemia and reinfarction occurred in 42 patients (3.4%), recurrent ischemia alone occurred in 226 (18%), whereas neither occurred in 964 (78%). Although baseline characteristics were similar among the 3 groups, in-hospital cardiac events (total 73 deaths, 253 heart failure episodes) were not: in-hospital mortality in patients with reinfarction was 21%; with recurrent ischemia, 11%; and with neither event, 4% (p < 0.0001). The in-hospital heart failure rate of patients with reinfarction was 50%; with recurrent ischemia alone, 31%; and with neither event, 17% (p < 0.0001). As expected, median in-hospital costs were highest in patients with reinfarction ($26,802), intermediate for those with recurrent ischemia alone ($18,422), and lowest in patients with neither event ($15,623). Recurrent myocardial ischemia after thrombolytic therapy is a frequent, important, and expensive adverse clinical outcome, making it a critical target for therapeutic intervention.

Computer-assisted intraoperative mapping of the entire ventricular epicardium in the Wolff-Parkinson-White syndrome.

Intraoperative mapping with a hand-held, roving electrode requires a sustained rhythm lasting 5 to 10 minutes. To overcome this limitation, a computerized mapping system that records from 60 epicardial electrodes simultaneously was used to study 16 patients with Wolff-Parkinson-White syndrome. A sock containing 6 rows of electrodes arranged concentrically from base to apex was place over the ventricles. The total time from placing the sock to analyzing the most basal row of electrode recordings was 5 minutes. A 39 X 44-mm plaque containing 56 electrodes was than placed across the atrioventricular (AV) groove for detailed simultaneous mapping of the ventricle and atrium in the preexcited region identified from the most basal row of sock electrodes. During plaque placement and recording, the remaining sock recordings were analyzed and a complete isochronal epicardial map was drawn. The plaque recordings were then analyzed. This technique rapidly detects early activation at the AV groove as do other computer systems using only a band of electrodes around the AV groove. Also, complete epicardial mapping supplied important additional information. One patient with a posterior paraseptal accessory pathway had ventricular epicardial breakthrough below the strip recorded by the AV band. When more than 1 early activation site was present along the AV groove, complete maps allowed multiple pathways to be differentiated from normal activation fronts ascending from the bundle branches. Complete epicardial maps allowed the study of rapidly changing or short-lived electrical events including isolated premature impulses, initiation and termination of reciprocating tachycardia by pacing, entrainment and changing degrees of fusion created by pacing during reciprocating tachycardia, and ventricular responses during atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cox/maze procedure for atrial septal defect with atrial fibrillation: management strategies.

Atrial fibrillation is found at late follow-up in approximately half of all adults who have had correction of atrial septal defect, even if it was not present preoperatively. These patients are thus exposed to the risks of stroke and chronic drug therapy even after a successful operation. Simultaneous surgical correction of atrial septal defect and atrial fibrillation was accomplished in a 52-year-old man by means of the Cox/maze procedure. The small added risk and the substantial benefit of eliminating atrial fibrillation suggest that this approach is warranted in selected adults with atrial septal defect.

Use of a real-time three-dimensional magnetic navigation system for radiofrequency ablation of accessory pathways.

Using conventional technology, accessory pathway ablation often requires prolonged exposure of the team and patient to ionizing radiation. Further, although the primary success rate (approximately 90%) and the rate of recurrence (approximately 10%) are acceptable, there is room for improvement. Finally, inadvertent ablation of the compact node and AV/His-Purkinje system still occurs particularly with septal accessory pathways. The Biosense CARTO Nonfluoroscopic Mapping and Navigation System (CARTO System) when used to locate the accessory pathway and guide delivery of radio frequency energy to the accessory pathway, has the potential to reduce radiation exposure, improve primary ablation success, and reduce the rate of recurrence and improve safety. This article describes our experience with the CARTO Biosense System relating to setting up the CARTO System specifically for WPW mapping/ablation, and features of the CARTO System, which are particularly advantageous for mapping and ablation of accessory pathways.

Construction of a multipolar electrode system referenced and anchored to endocardium for study of arrhythmias.

We developed a Teflon plunge electrode system (Teflon plunge) with important advantages over currently used electrodes. The Teflon plunge consists of an anchor-introducer (anchor) attached to the tip of an 0.8-mm diam epoxy-filled Teflon tube supporting six bipolar recording sites. The plunge is inserted through the myocardium into the ventricular cavity perpendicular to the epicardium. Once in the left ventricular cavity the anchor at the tip of the plunge pivots perpendicular to the long axis of the plunge and seats on the endocardium. It is maintained in position with a 4-0 nylon line (line) that extends from its attachment to the anchor through the body of the plunge to the epicardial end where it is secured with a Ligaclip. Thus the electrode contacts are placed a predetermined distance from the endocardium. When the Ligaclip is released, the plunge is removed from the heart leaving the line in the track of the electrode attached to the anchor as a marker for histological studies. The Teflon plunge will facilitate the evaluation of the role of the endocardium in ventricular arrhythmias by locating recording sites a stable, known distance from the endocardium and by marking the electrode track for histological studies.

The effect of residual noise on the reproducibility of the signal-averaged electrocardiogram.

Signal averaging reduces noise in the surface ECG, allowing late potential identification. However, late potentials may vary within a patient from study to study. In a population with stable biopotentials, this work evaluated how residual noise (RN) affects signal-averaged ECG (SA-ECG) reproducibility.

Late fractionated potentials and continuous electrical activity caused by electrode motion.

Late fractionated potentials, recorded during cardiac mapping to find the source of a ventricular arrhythmia, have been ascribed particular localizing value. Re-entry is assumed when these highly amplified and filtered recordings span diastole during tachycardia. The purpose of this study was to see if such potentials can occur artifactually. A saline soaked 7 X 2 X 3 cm sponge was sewn to the epicardium of the right ventricle in five non-infarcted, open-chest dogs. Two bipolar button electrodes, one with 1 mm and one with 1 cm interelectrode spacing, were attached to the outer surface of the sponge and a bipolar wire hook electrode was placed just under the outer surface of the sponge. Thus all three electrodes were 3 cm from the nearest myocardium yet still subjected to cardiac motion. The electrodes were recorded at gains of 4,000-40,000 and filtered to pass 50-300 hertz. One to three rapid deflections were recorded during the QRS from all electrodes. In seven of the the 15 electrode recordings, two or three additional deflections, 1100-200 microV in amplitude, occurred after the QRS. These late potentials were fractionated and recurred reproducibly from cycle to cycle. In two cases, these late fractionated potentials could be made to span diastole by rapid pacing to simulate tachycardia. Clamping the sponge to sliminate motion between the sponge and electrode caused this late activity to disappear. Thus, in highly amplified and filtered recordings, electrode motion can cause artifacts resembling late fractionated potentials and continuous electrode activity.

A new sock electrode for recording epicardial activation from the human heart: one size fits all.

Simultaneous recording of epicardial activation from multiple sites during open heart surgery is essential for studying unstable ventricular arrhythmias. A previously described sock electrode array for this purpose requires custom-woven nylon sock material and expensive machined button electrodes. The limited compliance and elasticity of nylon requires that a new sock be individually fitted for each heart. Despite careful fitting, 17-20% of electrodes do not make satisfactory epicardial contact in dogs. Further, electrodes frequently dislodge from the sock and wires break at the button electrode solder joint. Recognizing these limitations, we formed a new sock from Xspan tubular dressing material and devised electrodes that attach securely to the sock. In six dogs, 90% +/- 3% of electrodes made satisfactory contact using the same Xspan sock, significantly (p less than .01) more than with the nylon sock despite far less labor. The same size X span sock with 60 snap electrodes was used to record from 27 human hearts of widely different dimensions. Satisfactory epicardial contact was obtained in 90% +/- 14% of electrodes in the 18 patients with Wolff-Parkinson-White syndrome (WPW) and 75% +/- 15% of electrodes in the nine patients with coronary artery disease. In no case did an accessory pathway fail to conduct following sock placement. The hemodynamic effect of the Xspan sock was evaluated in four dogs and was found to be minimal. Both the Xspan sock and the snap electrodes are easily made from inexpensive, readily available materials. The same Xspan sock accommodates a wide range of heart sizes, and the electrodes supported by the Xspan sock record significantly better and with less dislodgement and wire breakage than previous socks.

Signal averaging in Wolff-Parkinson-White syndrome: evidence that fractionated activation is not necessary for body surface high-frequency potentials.

It is commonly assumed that the presence of high frequency components in body surface potentials implies that fractionated activation fronts, caused by heterogeneously viable tissue, are present in the heart. However, it is possible that non-fractionated activation fronts can also give rise to high frequency surface potentials and that the relative amount of high frequency power is related to the complexity of the activation sequence. In a test of this idea, averaged body surface potentials were recorded during the entire QRS complex of nine Wolff-Parkinson-White (WPW) patients in situations in which fractionated activation fronts should not have been present, but which represent increasing degrees of complexity of ventricular activation: (1) postoperative ectopic pacing from subepicardial wires placed during surgery, when a single coherent activation front was present throughout most of the QRS; (2) Preoperative preexcited rhythm, when a single coherent activation front was present for one portion of the QRS (the delta wave); and (3) postoperative normal rhythm, when two or more activation fronts were present in the ventricles throughout most of the QRS. For comparison, averaged body surface potentials were also analyzed during the last 40 ms of the QRS complex and the ST segment of 14 postinfarction patients with chronic ventricular tachycardia. In the patients with WPW syndrome, relatively high frequency content increased (attenuation -36.7 vs -27.2 vs -18.3 dB) and QRS width decreased (160.7 vs 125.9 vs 94.1 ms) significantly from paced to preoperative to postoperative beats. Significant high frequency content was present in all cases, showing that coherent activation fronts can give rise to high frequencies. Interestingly, the postoperative QRS of WPW patients contained a larger proportion of high frequency power than did the late potentials of the patients with ventricular tachycardia. Thus, while the presence of late fractionated body surface potentials may be a marker for ventricular tachycardia, these potentials by themselves do not necessarily signify that the underlying cardiac activation giving rise to these signals is fractionated.

Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker Integrelin in elective coronary intervention. IMPACT Investigators.

BACKGROUND: Platelet aggregation and thrombosis have been implicated in the pathogenesis of coronary angioplasty complications. Integrelin, a synthetic cyclic heptapeptide with high affinity and marked specificity for platelet integrin glycoprotein IIb/IIIa, effectively blocks ADP-induced platelet aggregation. METHODS AND RESULTS: In 150 patients undergoing elective percutaneous coronary intervention, random assignment was made to one of three treatment regimens: placebo; a 90-micrograms/kg bolus of Integrelin before angioplasty followed by a 1.0-micrograms.kg-1.min-1 infusion of Integrelin for 4 hours; or a 90-micrograms/kg bolus followed by a 1.0-microgram.kg-1.min-1 infusion of Integrelin for 12 hours. Patients were followed to 30 days for the composite occurrence of myocardial infarction, stent implantation, repeat urgent or emergency percutaneous intervention or coronary bypass surgery, or death. Pharmacodynamic data were obtained in a subset of 31 patients. Administration of a 90-micrograms/kg bolus of Integrelin achieved an 86% inhibition of platelet aggregation, and this inhibition was maintained by a 1.0-microgram.kg-1.min-1 infusion. There was a trend toward reduction in end-point events from 12.2% (placebo) to 9.6% (4-hour infusion) to 4.1% (12-hour infusion), although these differences were not statistically significant (P = .13 for the 12-hour group compared with placebo). Major bleeding occurred in 8%, 8%, and 2% of patients, while minor bleeding was observed in 14%, 33%, and 47% of patients, respectively. There was no difference in bleeding index among groups (1.5, 1.7, and 1.3, respectively), defined as [(change in hematocrit/3)+red blood cell units transfused]. CONCLUSIONS: This first clinical investigation of Integrelin during routine, elective, low- and high-risk coronary intervention supports the potential efficacy of Integrelin in routine coronary interventions. Pharmacodynamic analyses demonstrate that profound and sustained inhibition of platelet function is achieved, although a higher bolus dose may be required. Definitive assessment of efficacy and safety will need to await a large-scale study powered to achieve statistical significance.