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R Lazzara

Publications and source records attributed to R Lazzara.

At least 73 records · Page 4Linked to original sources
PubMed1995

Optimal filtering and quality control of the signal-averaged ECG. High-fidelity 1-minute recordings.

BACKGROUND: The clinical performance of the signal-averaged ECG (SAECG) for prediction of ventricular tachycardia (VT) depends on its quality, or final noise level. However, signal averaging is a statistical estimation procedure that is time-consuming and vulnerable to noise-induced error. The optimally filtered SAECG is proposed as a simple, quality-assured procedure requiring only 1 minute of data. METHODS AND RESULTS: The optimally filtered SAECG is based on measures of signal variance and time-frequency representations. Forty subjects were studied to compare a 0.3-microV root-mean-square (RMS) noise endpoint SAECG with an optimally filtered 64-beat ensemble. Eight SAECGs were computed with noise endpoints of 1.0-through 0.3-microV RMS. Noise measurements were also made directly from the filtered SAECG. From these and previously published data, sensitivity was predicted as a function of noise endpoint. Measured QRS parameters and final noise were highly similar between the optimally filtered SAECG and the 0.3-microV RMS noise endpoint SAECG. CONCLUSIONS: The optimally filtered 64-beat SAECG achieves a performance (equivalent noise reduction, signal definition, and mathematically predicted sensitivity for VT) similar to a 0.3-microV RMS noise endpoint average. Testing in a large clinical database is required to validate the method for routine clinical use. SAECGs terminated by use of different noise measurement techniques are not directly comparable because of measurement technique dependence. However, a formula is presented for comparison of statistics between studies that have used the most popular noise measurement techniques.

Electrocardiography↗
PubMed1995

Clinical investigation of antiarrhythmic devices. A statement for healthcare professionals from a joint task force of the North American Society of Pacing and Electrophysiology, the American College of Cardiology, the American Heart Association, and the Working Groups on Arrhythmias and Cardiac Pacing of the European Society of Cardiology.

The goal of radiofrequency catheter ablation and the criterion for efficacy is the elimination of arrhythmogenic myocardium. The application of radiofrequency current in the heart clearly results in lower morbidity and mortality rates than thoracic and cardiac surgical procedures in general, and comparisons of therapy with radiofrequency catheter ablation and therapy with thoracic and cardiac surgical procedures in randomized clinical trials is unwarranted. Trials of radiofrequency catheter ablation versus medical or implantable cardioverter-defibrillator therapy may be indicated in certain conditions, such as ventricular tachycardia associated with coronary artery disease. Randomized trials are recommended for new and radical departures in technology that aim to accomplish the same goals as radiofrequency catheter ablation. Surveillance using registries and/or databases is necessary in the assessment of long-term safety and efficacy.

American Heart Association↗
PubMed1995

Sympathetic activation, ventricular repolarization and Ikr blockade: implications for the antifibrillatory efficacy of potassium channel blocking agents.

OBJECTIVES: The aim of the present study was to test, in vivo and in vitro, the influence of adrenergic activation on action potential prolongation induced by the potassium channel blocking agent d-sotalol. BACKGROUND: d-Sotalol is not effective against myocardial ischemia-dependent ventricular fibrillation in the presence of elevated sympathetic activity. Most potassium channel blockers, such as d-sotalol, affect only one of the two components of Ik (Ikr) but not the other (Iks). Iks is activated by isoproterenol. An unopposed activation of Iks might account for the loss of anti-fibrillatory effect by d-sotalol in conditions of high sympathetic activity. METHODS: In nine anesthetized dogs we tested at constant heart rate (160 to 220 beats/min) the influences of left stellate ganglion stimulation on the monophasic action potential prolongation induced by d-sotalol. In two groups of isolated guinea pig ventricular myocytes we tested the effect of isoproterenol (10(-9) mol/liter) on the action potential duration at five pacing rates (from 0.5 to 2.5 Hz) in the absence (n = 6) and in the presence (n = 8) of d-sotalol. RESULTS: In control conditions, both in vivo and in vitro, adrenergic stimulation did not significantly change action potential duration. d-Sotalol prolonged both monophasic action potential duration in dogs and action potential duration of guinea pig ventricular myocytes by 19% to 24%. Adrenergic activation, either left stellate ganglion stimulation in vivo or isoproterenol in vitro, reduced by 40% to 60% the prolongation of action potential duration produced by d-sotalol. CONCLUSIONS: Sympathetic activation counteracts the effects of potassium channel blockers on the duration of repolarization and may impair their primary antifibrillatory mechanism. An intriguing clinical implication is that potassium channel blockers may not offer effective protection from malignant ischemic arrhythmias that occur in a setting of elevated sympathetic activity.

Action Potentials↗
PubMed1995

A technique for stable His-bundle recording and pacing: electrophysiological and hemodynamic correlates.

His-bundle electrograms recorded from intracardiac electrode catheters have been a mainstay of basic and clinical electrophysiology. However, consistent His-bundle pacing has not been as readily achieved. In 13 dogs anesthetized with sodium pentobarbital (30 mg/kg), we recorded leads II and aVR as well as the His-bundle electrogram from the aortic root. A deflectable tip multipolar catheter (4 rings, 5 mm apart) was introduced via the right jugular vein into the right ventricle (RV). In 7 dogs, using fluoroscopy, the tip was placed under the tricuspid septal leaflet. In the other 6, after thoracotomy, the same placement was made by palpation through the right atrial wall. Stable His-bundle and right bundle (Rb) branch recordings were made from distal and proximal electrode pairs, respectively. H-V intervals measured 35 +/- 6 ms from the aortic root and 33 +/- 5 ms from under the tricuspid leaflet (P = NS). Rb-V measured 25 +/- 4 ms. Consistent His-bundle pacing was accomplished from the aortic root with an average stimulus intensity of 6 +/- 10 mA and from the tricuspid leaflet at 16 +/- 8 mA (P < 0.05). In 7 anesthetized dogs we compared the hemodynamic effects of A-V sequential pacing at the same heart rates using the His-bundle recording site under the septal leaflet of the tricuspid valve (A-H pacing) or pacing from the RV apex (A-RV pacing). Under normal conditions there was a significant depression of mean blood pressure when A-RV pacing was compared with atrial pacing (AOO); but no difference was found between AOO and A-H pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

NASPE/ACC/AHA/ESC medical/scientific statement special report--clinical investigation of antiarrhythmic devices: a statement for healthcare professionals from a Joint Task Force of the North American Society of Pacing and Electrophysiology, the American College of Cardiology, the American Heart Association, and the Working Groups on Arrhythmias and Cardiac Pacing of the European Society of Cardiology.

The goal of radiofrequency catheter ablation and the criterion for efficacy is the elimination of arrhythmogenic myocardium. The application of radiofrequency current in the heart clearly results in lower morbidity and mortality rates than thoracic and cardiac surgical procedures in general, and comparisons of therapy with radiofrequency catheter ablation and therapy with thoracic and cardiac surgical procedures in randomized clinical trials are unwarranted. Trials of radiofrequency catheter ablation versus medical or implantable cardioverter defibrillator therapy may be indicated in certain conditions, such as ventricular tachycardia associated with coronary artery disease. Randomized trials are recommended for new and radical departures in technology that aim to accomplish the same goals as radiofrequency catheter ablation. Surveillance using registries and/or databases is necessary in the assessment of long-term safety and efficacy.

Arrhythmias, Cardiac↗
PubMed1995

Role of calcium loading in early afterdepolarizations generated by Cs+ in canine and guinea pig Purkinje fibers.

INTRODUCTION: Our previous observations indicate that the Na+:Ca2+ exchange current (INa:Ca) plays an important role in early afterdepolarizations occurring at more negative Vm (L-EAD). The purpose of these studies was to examine the role of Ca(2+)-loading, which stimulates INa:Ca, in generation of L-EAD. METHODS AND RESULTS: Purkinje strands and preparations of ventricular myocardium from dogs and guinea pigs were superfused with oxygenated physiologic buffer solutions at 37 degrees C. To induce EADs, [K+]o was reduced to 2.0 to 3.0 mM and [Cs+]o (3.6 to 4.0 mM) was added at slow rates of < or = 0.3 Hz. Isometric contraction in canine Purkinje strands and guinea pig papillary muscles doubled in 1-hour exposure to Cs+ and low [K+]o at slow rates and the uptake of 45Ca2+ was approximately doubled after 30 minutes. Forty-three percent of Purkinje fibers developed L-EAD after a latent period of 17 to 123 minutes of exposure. Ouabain (0.2 microM) suppressed L-EAD within 10 minutes reversibly. Ca(2+)-loading (low [Na+]o or high [Ca2+]o) for 5 to 10 minutes before exposure to Cs+, low [K+]o, and slow rates resulted in rapid development of L-EAD in all preparations during subsequent exposure. In Ca(2+)-loaded preparations, delayed afterdepolarizations (DADs) as well as L-EADs developed. CONCLUSIONS: Reduction of K+ currents with Cs+, low [K+]o, and slow rates induced L-EAD in a fraction of Purkinje fibers after a latent period during which Ca(2+)-loading of the sarcoplasmic reticulum occurred, while fibers preloaded with Ca2+ developed L-EAD rapidly and uniformly. These findings indicate that Ca(2+)-loading is a critical condition for the development of L-EAD. Early suppression of L-EAD by ouabian suggests a dependence of L-EAD on low [Na+]i. These findings implicate INa:Ca in the generation of L-EAD.

Animals↗
PubMed1995

Pharmacokinetics and plasma protein binding of the new potent class III antiarrhythmic agent 3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3, 7-diazabicyclo[3.3.1]nonane dihydroperchlorate.

GLG-V-13 (3-[4-(1H-imidazol-1-yl)benzoyl]-7-isopropyl-3,7-diazabicyclo [3.3.1] nonane dihydroperchlorate, CAS 155029-33-7) has been shown to be a potent class III antiarrhythmic agent. The oral and intravenous pharmacokinetics and plasma protein binding of GLG-V-13 in dogs and in rabbits have now been investigated. Plasma GLG-V-13 concentration-time profiles, following an i.v. bolus dose of 6 mg/kg, were fitted to a 2-compartment model. The volume of distribution at steady state (Vd(ss)), the total systemic (ClB), and the elimination half-life (t1/2 beta) were 4.441 l/kg, 1.113 l/h/kg, and 2.485 h in dogs and 3.723 l/kg, 1.548 l/h/kg, and 1.401 h in rabbits. Following i.v. dosing, approximately 9.38% of the parent compound was excreted in dogs urine (0-72 h). Changes in plasma GLG-V-13 concentrations, after oral administration of GLG-V-13 (6 mg/kg), were best described by the 1-compartment pharmacokinetic model. The tmax and Cmax were 1.69 h, 0.54 mg/l in dogs and 1.44 h, 0.35 mg/l in rabbits. On oral administration, GLG-V-13 was moderately eliminated (t1/2kel' 1.867 h-1 in dogs and 3.961 h-1 in rabbits, respectively). Oral bioavailability was estimated to be 53.2% +/- 11.3% in dogs and 66.7% +/- 7.7% in rabbits. About 8.74% of the oral dose (6 mg/kg) was excreted via the dog urine (0-72 h). In vitro binding of GLG-V-13 to dog plasma protein was 29.4 +/- 9.90% (from 0.5 to 4 mg/l). Ex vivo binding of GLG-V-13 to dog plasma protein was 10.4 +/- 7.20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Electrophysiological characterization of a novel class III antiarrhythmic agent, GLG-V-13 in the mammalian heart.

GLG-V-13, a novel 3,7-diheterabicyclo[3.3.1]nonane, was examined both in vivo and in vitro in order to characterize its electrophysiological, haemodynamic and inotropic properties. Left ventricular epicardial monophasic action potential (MAP), surface ECG and mean arterial blood pressure (MBP) were recorded in six pentobarbital-anaesthetized, artificially ventilated and thoracotomized guinea-pigs. When studied in an intravenous dose interval ranging between 0.5 micrograms/kg and 500 micrograms/kg, GLG-V-13 dose-dependently lengthened the MAP duration (p < 0.05 at doses above 5 micrograms/kg), the atrioventricular conduction time (p < 0.05 at doses above 1 microgram/kg) and the RR interval (p < 0.05 at doses above 25 micrograms/kg). At the highest dose (500 micrograms/kg) these variables were increased by 30%, 13% and 23%, respectively. Only minor effects were noted on intraventricular conduction time (QRS interval) and MBP. In rabbit atrial and papillary muscle preparations, GLG-V-13 (0.32 to 3.2 mg/l) did not exert negative inotropic action. In 10 intact anaesthetized mongrel dogs, left ventricular endocardial MAP at 90% repolarization (MAP90) was measured during atrial pacing before and after administration of GLG-V-13, 3 and 6 mg/kg i.v., respectively.

Action Potentials↗
PubMed1995

Atrial inputs as determinants of atrioventricular nodal conduction: re-evaluation and new concepts.

Radiofrequency ablation was combined with standard recording and pacing procedures to determine the role of the perinodal fast pathway (FP) and slow pathway (SP) in atrioventricular (A-V) conduction in normal dog hearts. In 16 anesthetized, open-chest dogs, we recorded atrial (A) electrograms from the high right atrium (HRA), His bundle (Hb) region and coronary sinus (CS) ostium. In 8 dogs, during HRA pacing at a cycle length of 400 ms, FP ablation induced a significant change in A-H interval (61 +/- 12 to 107 +/- 9 ms, p < 0.001) but no change in Wenckebach cycle length (185 +/- 14 to 190 +/- 12 ms, NS). During ventricular pacing (400 ms cycle length) there was a shift in retrograde atrial activation so that Hb (A) delayed more than CS (A). Subsequent SP ablation in this same group of 8 dogs, produced a significant prolongation of antegrade Wenckebach cycle length (190 +/- 10 to 277 +/- 36 ms, p < 0.002) but only one instance of complete A-V block even though both FP and SP were ablated in accordance with clinical criteria. In another group of 8 dogs, a specially designed ablation electrode was inserted into the right atrium and positioned at the level of the fossa ovalis, 10-12 mm superior to the perinodal area. A radiofrequency linear lesion across the interatrial system induced a marked PR interval prolongation due to an intra-atrial rather than A-V nodal delay. The A-H interval was unchanged, and there was no change in antegrade or retrograde Wenckebach cycle length. In contrast, to the findings in both these groups direct damage to the A-V node showed immediate change in the A-H interval and at the same time progression to second degree and complete heart block. Taken together these results suggest that the perinodal FP and SP are composed of transitional cells which possess distinct electrophysiological properties not shared by adjacent atrial tissues or the compact A-V node itself. We conclude that the persistence of A-V conduction, albeit modified, after FP and SP ablation, suggests the existence of multiple atrio A-V nodal inputs whereas retrograde conduction relies mainly on dual exits from the A-V node to the atria.

Animals↗
PubMed1995

A four-year retrospective study of 3i threaded implants.

The use of osseointegrated implants can be considered as one of the most productive developments in dentistry during this century. Although initially introduced for use in fully edentulous patients, their present widespread use in nearly all forms of tooth loss, as well as for the rehabilitation of maxillofacial prosthetics and in orthodontics, has significantly expanded the realm of restorative dentistry. The present multicentre retrospective study evaluates the results of 327 patients rehabilitated with 1047, 3i (Implant Innovations Inc.) threaded implants over a four-year period. Eight patients with 22 implants dropped out and were excluded from the study as they could not be evaluated. A total of 319 patients with 1025 implants remained. Nine implants failed in the mandible and 14 in the maxilla. There was a success rate of 98.2 percent in the mandible and 97.3 percent in the maxilla. The mean overall success rate was 97.75 percent, with little variation between the four study centres. These results are similar to previously published studies on titanium threaded implants and indicate that, with careful adherence to accepted principles of surgery and restorative dentistry, the 3i threaded implant system can be used confidently to provide the necessary support for an osseointegrated implant-supported prosthesis.

Adolescent↗
PubMed1994

Facilitation of reentry by lidocaine in canine myocardial infarction.

The authors studied the effects of lidocaine in 18 consecutive dogs with myocardial infarction 1 to 4 days after two-stage left anterior descending coronary artery ligation. Electrophysiologic testing was performed in anesthetized dogs after infarction with single-, double-, or triple-programmed extrastimuli or rapid bursts (3 beats at 240 to 420 beats/min) delivered to the right ventricular outflow tract. Inducibility of sustained monomorphic ventricular tachycardia after an intravenous bolus of lidocaine (3 to 6 mg/kg) was compared in the same animal to the premedicated state. In the control state, sustained monomorphic ventricular tachycardia was inducible in 6 of 18 dogs. After administration of lidocaine, electrically induced sustained monomorphic ventricular tachycardia was initiated in an additional nine dogs (which were previously noninducible; after lidocaine administration vs control p < 0.02). The antiarrhythmic agent induced further rate-dependent slowing of conduction in the periinfarction subepicardium, which at a critical value of rate and amount of conduction delay resulted in sustained reentrant monomorphic tachycardia. These results show that lidocaine has marked proarrhythmic action in this canine model of myocardial infarction, probably because of its depressant effect on injured cardiac tissue.

Animals↗
PubMed1994

Time-frequency structure of the high-resolution ECG.

This study considers the problem of representing high-resolution ECG (HRECG) signals in the time-frequency plane using spectrotemporal mapping (STM). High-resolution ECG signal components overlap in both time and frequency. The central issue with STM techniques is whether sufficient time-frequency resolution exists to discriminate normal and abnormal QRS signals. The trade-off between signal resolution in time and in frequency must be made without a priori knowledge of the HRECG's time-frequency structure. A simulation experiment was performed to examine the time-frequency distribution of normal, abnormal low-level (late potentials), and bundle branch block components of the QRS. Results suggest that discrimination of these signals with STM is problematic. Signals and noise within the HRECG ensemble can, however, be easily distinguished. This observation forms the basis of a new optimally filtered ensemble averaging technique for signal-to-noise ratio enhancement.

Electrocardiography↗
PubMed1994

Late potentials are unaffected by radiofrequency catheter ablation in patients with ventricular tachycardia.

Reentrant ventricular tachycardia is dependent on an area of myofibers, embedded in scar tissue, which exhibit slow conduction. Late potentials recorded by signal-averaged electrocardiography appear to correspond to these zones of slow conduction and frequently are present in patients with VT. We hypothesized that elimination of inducible VT by catheter-mediated ablation of critical areas of slow conduction would alter late potentials. Four patients underwent catheter ablation in which radiofrequency current was delivered to zones of slow conduction exhibiting isolated mid-diastolic potentials that could not be dissociated from the tachycardia. The four patients had developed VT (cycle length 382 +/- 50 msec; mean +/- SEM) 13-180 months after inferior myocardial infarction. Late potentials were present in each patient before catheter ablation was attempted. Although VT was not inducible in any patient immediately after ablation, late potentials were still present in all four patients and there was no significant difference in the QRS duration (136.5 +/- 4.0 msec postablation; 135.7 +/- 4.5 msec preablation), root mean square voltage in the terminal 40 msec of the QRS (10.0 +/- 1.0 microV postablation; 5.9 +/- 0.4 microV preablation), or in the duration of the low amplitude signal (69.2 +/- 2.0 msec postablation; 62.7 +/- 3.4 msec preablation). At follow-up electrophysiology study performed 14 +/- 7 days after ablation, one of the four patients had inducible VT. In conclusion, late potentials persist even after successful radiofrequency catheter ablation and do not appear to be useful for predicting results of follow-up electrophysiology study.

Action Potentials↗
PubMed1994

Results of Holter ECG guided therapy for ventricular arrhythmias: the ESVEM trial.

The Electrophysiological Study Versus Electrocardiographic Monitoring (ESVEM) trial randomized 486 patients with spontaneous sustained ventricular tachycardia (VT), ventricular fibrillation (VF) or unmonitored syncope, who manifested reproducibly inducible sustained ventricular arrhythmias by provocative stimulation and 10 or more premature ventricular contractions per hour on Holter monitoring, to two groups treated with pharmacotherapy guided by suppression of stimulation-inducible VT/VF or suppression of spontaneous or exercise induced ventricular arrhythmias. There was no difference over four years of follow-up in the rates of recurrence of arrhythmias, arrhythmic mortality, cardiac mortality, or mortality from any cause between the two groups of patients but more patients (77%) received pharmacotherapy in the group treated on the basis of suppression of spontaneous arrhythmias than the group treated on the basis of electrophysiological study. In this trial, rates of recurrence of arrhythmias were higher (37% at one year and 66% at four years) than generally reported, but cardiac and arrhythmia mortality were comparable or lower than generally reported. Of the seven agents tested, six were sodium channel blockers (imipramine, mexiletine, procainamide, propafenone, pirmenol, and quinidine) and the other was sotalol. Sotalol had a significantly higher rate of efficacy predictions by EPS (35%) than the others (15%) and a comparable rate by Holter monitor. Sotalol was significantly more efficacious in preventing recurrences, arrhythmic mortality, cardiac mortality, and total mortality than the other agents and it was better tolerated. Probability of successful long term therapy with a sodium channel blocker tested by electrophysiological study was low (5% at one year).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1994

Identifying the end of ventricular activation: body surface late potentials versus electrogram measurements in a canine infarction model.

INTRODUCTION: Identification of the end of the QRS is perhaps the single most important feature obtained from the high resolution signal-averaged electrocardiogram (SAECG). This point relies on computer algorithms to select a point above the noise levels. Prior studies to substantiate this approach using electrograms for comparison have demonstrated many examples of the body surface recordings failing to detect the full extent of the late potentials. METHODS AND RESULTS: An animal model that generates late potentials was used in conjunction with epicardial cardiac mapping system to systematically examine the reasons for these failures. In 11 of 13 dogs we found a concordance between the signal-averaged recordings and the epicardial recordings within 5 msec. The two discordant studies were attributed to a failure of epicardial mapping to record all late potential sources. Also, a means of accurately comparing measurements from the two recording technologies was required in this study as well as a new definition for identifying the end of activation currents in epicardial electrograms. CONCLUSION: To achieve these results required approaches different from those used in the clinical setting to record the SAECG. These include: (1) the analysis of individual XYZ leads as opposed to the vector magnitude derived from these leads; (2) visual identification of very low level signals, as automatic algorithms often fail to detect low level signals; and (3) the use of finite impulse response digital filters instead of the bidirectional Butterworth filter.

Action Potentials↗