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Biomedical subjects

R N Fogoros

Publications and source records attributed to R N Fogoros.

At least 19 recordsLinked to original sources

Long-term outcome of survivors of cardiac arrest whose therapy is guided by electrophysiologic testing.

The long-term outcome of 217 consecutive survivors of cardiac arrest whose therapy was guided by electrophysiologic testing was analyzed. After electrophysiologic testing, 81 patients (37%) were classified as having no inducible arrhythmia and were treated without antiarrhythmic drugs; 23 received an implantable defibrillator. Of the 136 patients with inducible arrhythmia, the 51 (38%) who responded to serial drug testing were treated with the successful drug and the 85 (62%) with unsuccessful drug testing were treated with an implantable defibrillator (47 patients), amiodarone (36 patients) or drugs that were unsuccessful during testing (2 patients). The mean follow-up interval for all patients was 35 +/- 23 months. The actuarial incidence of sudden death and overall death was similar for patients whose arrhythmias were not inducible, drug responders and nonresponders. The actuarial incidence rate of recurrent arrhythmic events in nonresponders was 35 +/- 5% and 53 +/- 7% at 2 and 5 years, respectively. These values were significantly lower (and statistically similar to each other) in the other two patient groups: patients with noninducible arrhythmia (19 +/- 5% and 31 +/- 7%, respectively, p less than 0.05) and drug responders (13 +/- 5% and 23 +/- 8%, respectively, p less than 0.01). Patients with an implantable defibrillator who had recurrent arrhythmic events were significantly less likely to die suddenly than were patients without a defibrillator who had recurrent events (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis

Long-term multicenter experience with a second-generation implantable pacemaker-defibrillator in patients with malignant ventricular tachyarrhythmias. The Guardian Multicenter Investigators Group.

A second-generation implantable pacemaker-cardioverter-defibrillator was evaluated in 200 patients with sustained ventricular tachycardia, ventricular fibrillation or prior cardiac arrest. The device permits demand ventricular pacing for bradyarrhythmias and for long QT interval or tachycardia suppression, uses programmable (3 to 30 J) energy shocks for conversion of ventricular tachycardia and ventricular fibrillation and is used with conventional pacing and defibrillation leads. Ventricular tachycardia/fibrillation recognition is based on the ventricular electrogram rate and requires reconfirmation before shock delivery. Two hundred patients (mean age 62 years, mean left ventricular ejection fraction 36%) were enrolled and followed up for 0 to 23 months (mean 12). Epicardial lead system implantation was performed with use of an anterolateral thoracotomy (38%), median sternotomy (26%) and subxiphoid (20%) or subcostal (16%) approach. Perioperative mortality rate was 5.5% (all nonarrhythmic deaths). Implant defibrillation threshold ranged from 3 to 30 J (mean 15), with initial programmed shock energy ranging from 3 to 30 J (mean 22). Ventricular tachycardia/fibrillation sensing threshold ranged from 0.7 to 1.8 mV (median 1) and the tachycardia detection interval from 288 to 416 ms (median 320). Reprogramming of implant variables was necessary for reliable electrographic sensing (54 patients), programmed shock therapy (61 patients) and tachycardia detection rate (63 patients). Device activation for potential shock delivery occurred in 111 patients (55.5%) with actual shock delivery after ventricular tachycardia/fibrillation reconfirmation in 66 patients (33%). During follow-up study, there was a 1% arrhythmia mortality rate, 6.5% cardiac mortality rate and 10.5% total mortality rate. This study demonstrates that the programmable implantable pacemaker-cardioverter-defibrillator is effective in preventing arrhythmic death, yet reduces patient exposure to repeated shock therapy. Reprogramming is usually necessary during follow-up for optimal function.

Adolescent

How useful are implantable cardioverter-defibrillators?

When use of an implantable cardioverter-defibrillator (ICD) is being considered for a patient with life-threatening ventricular arrhythmias, the potential risks and benefits must be carefully weighed. The risks of implantation of an ICD should be minimal; however, a low risk is highly dependent on patient selection and other factors, and perioperative risk varies significantly from center to center. The referring physician should not hesitate to ask for perioperative mortality statistics from the referral center. The difficulty in successfully documenting the usefulness of the ICD is especially important today. As the ICD becomes more like the pacemaker, there will be a natural tendency to expand the use of this new technology to patients in lower-risk groups. Suboptimal methods were adequate to document the benefit of the ICD in high-risk patients, but similar methods may not be adequate for low-risk patients. Fortunately, the importance of performing adequate studies has been recognized, as evidenced by the several randomized controlled trials that have been undertaken to study the efficacy of the ICD in these new groups of patients.

Arrhythmias, Cardiac

Reproducibility of successful drug trials in patients with inducible sustained ventricular tachycardia.

Patients whose inducible sustained ventricular tachycardia is suppressed during serial electrophysiological testing have a small but gradually increasing actuarial incidence of recurrent arrhythmias despite therapy with the "successful" drug. In an effort to improve the predictive value of a drug response, in 1990 we began to require that our full stimulation protocol be repeated successfully several times before considering a drug to be effective. In 23 consecutive patients who had inducible sustained ventricular tachycardia which was suppressed by at least one drug during invasive serial drug testing using a standard stimulation protocol, the identical stimulation protocol was performed six times during therapy with the initially successful drug (three trials on Day 1 and three trials on Day 2). Repeat trials were completed (i.e., either all six trials were successfully finished or sustained tachycardia was induced) for 29 initially successful drugs in these 23 patients. With 18 of these 29 initially successful drugs (62%), sustained ventricular tachycardia was eventually induced during repeat trials. The eventual drug failures could not be correlated with specific drugs tested, subtherapeutic or falling serum drug levels, marked fluctuations in autonomic tone, or changes in anatomic substrate. The proportion of patients failing each repeat trial was relatively constant: 4/29 (14%) failed Trial 2, 2/25 (8%) failed Trial 3, 7/23 (30%) failed Trial 4, 2/16 (13%) failed Trial 5, and 3/14 (21%) failed Trial 6. The increase in the cumulative incidence of drug failure during repeat trials was nearly linear. Inducibility of ventricular tachycardia appears to be a probability function; a successful drug study should not be regarded as an absolute phenomenon.

Adolescent

Long-term efficacy of an antitachycardia pacemaker and implantable defibrillator combination.

Antitachycardia pacemakers and implantable cardioverter defibrillators (ICD) were implanted in 14 patients to control recurrent hemodynamically stable ventricular tachycardia (VT). All patients underwent extensive preimplant testing in the electrophysiology laboratory documenting that in each patient at least 50 episodes of VT could be reliably terminated by an external model of the antitachycardia pacemaker. The burst scanning mode of antitachycardia pacing was used in all patients. ICDs were implanted solely as a back up should acceleration of VT occur, and all had high nonprogrammable rate cutoffs (mean 191 +/- 12 beats/min). During a mean follow-up of 25 +/- 6 months, 6,029 episodes of VT were treated in the 14 patients. Only 103 ICD discharges were required (approximately one discharge per 60 episodes of VT). Ten of the 14 patients received discharges from their ICDs. No deaths have occurred. All devices remain active and in the automatic mode. Thus, an antitachycardia pacemaker and ICD combination can safely and effectively terminate VT in highly selected patients who are subjected to extensive preimplant testing. In such patients, the vast majority of episodes of VT can be terminated with antitachycardia pacing, and only rarely is a discharge required from the ICD.

Aged

Efficacy of the automatic implantable cardioverter-defibrillator in prolonging survival in patients with severe underlying cardiac disease.

The ability of the automatic implantable cardioverter-defibrillator to prolong overall survival, particularly in patients with significantly depressed cardiac function, has not been well documented. Of 119 patients who received the implantable defibrillator in this institution, 40 had a left ventricular ejection fraction less than 30% (Group A) and 79 had an ejection fraction greater than or equal to 30% (Group B). For each group, cumulative survival was compared with the projected survival if the implantable defibrillator had not been used. Projected survival was based on the assumption that the first appropriate shock would have resulted in death without the defibrillator. For Group A, the 3 year cumulative survival rate was 67 +/- 12% versus a projected survival rate of 6 +/- 15% (p less than 0.001). For Group B, the 3 year cumulative survival rate was 96 +/- 3% versus a projected survival rate of 46 +/- 8% (p less than 0.001). Both the cumulative and projected survival rates for patients in Group A were significantly worse than for patients in Group B (p less than 0.01). The projected survival rates for both Groups A and B were comparable with the observed survival rate in similar patients treated without the implantable defibrillator. In summary, the implantable cardioverter-defibrillator significantly prolonged overall survival, even in patients with poor cardiac function. The technique of estimating projected survival appears to allow a realistic estimate of the reduction in mortality achieved by the defibrillator.

Adult

Actuarial incidence and pattern of occurrence of shocks following implantation of the automatic implantable cardioverter defibrillator.

The actuarial incidence and pattern of occurrence of shocks were analyzed in 65 patients after implantation of the automatic implantable cardioverter defibrillator. During a mean follow-up of 25 +/- 21 months only one patient died suddenly, and this patient had a nonfunctioning device at the time of death. The long-term actuarial risk of death from any cause in the patients who received appropriate shocks was not significantly different than for the entire group. The 1- and 4-year cumulative risk of receiving any shock was 51 +/- 7% and 81 +/- 11%; of receiving an appropriate shock was 33 +/- 7% and 64 +/- 10%; of receiving a spurious shock was 17 +/- 5% and 21 +/- 6%; and of receiving an "indeterminate" shock was 19 +/- 6% and 52 +/- 10%. In 14 patients who were followed for 24 months without receiving an appropriate shock, the actuarial risk of receiving an appropriate shock was 29 +/- 14% during the next 24 months. The mean number of shocks delivered during appropriate episodes was 1.6 +/- 0.9, which was significantly lower than the mean of 4.0 +/- 2.0 shocks during spurious episodes (P less than 0.02). The mean number of shocks during indeterminate episodes was 1.7 +/- 1.5. Our data confirms the efficacy of the implantable defibrillator in preventing sudden death. The majority of patients with this device receive appropriate shocks during long-term follow-up, and the cumulative incidence of appropriate shocks increases steadily for at least 4 years. In contrast, the cumulative incidence of spurious shocks plateaus at about 12 months. Our data suggests that many "indeterminate" shocks actually appear to be appropriate.

Actuarial Analysis

Long-term prognosis of patients undergoing electrophysiologic studies for syncope of unknown origin.

Long-term prognosis was determined in 70 patients with unexplained syncope who underwent electrophysiologic testing between April 1981 and April 1986. The electrophysiologic study had positive results in 37 patients--31 with ventricular tachycardia, 3 with supraventricular tachycardia and 3 with abnormal conduction. There was no significant difference in the 3-year actuarial recurrence rate between the positive and negative outcomes (32 vs 24%, respectively). At 3 years, patients with positive outcomes had higher rates of sudden death than patients with negative results (48 vs 9%, respectively, p less than 0.002). The 3-year total mortality rate was also markedly higher in patients with positive results than among those with negative outcomes (61 vs 15%, respectively, p less than 0.001). Multivariate analyses showed mortality to be independently associated with unsustained ventricular tachycardia on prolonged electrocardiographic monitoring. It was concluded that patients with electrophysiologically positive results had high rates of sudden death and total mortality that have not been previously well recognized.

Bundle-Branch Block

Efficacy of phenytoin in suppressing inducible ventricular tachyarrhythmias.

We examined the efficacy of phenytoin in 69 of 87 consecutive patients undergoing serial electrophysiologic studies for inducible sustained ventricular tachycardia or fibrillation (VT/VF). In general, during the initial session lidocaine and procainamide were tested immediately after baseline electrophysiologic evaluation, followed by phenytoin and quinidine during the next two sessions, and then by additional drugs as needed. Once a successful drug was identified, all testing was stopped. Drugs that had failed in prior empiric trials were not tested. Twenty-five of the 87 patients (28.7%) had success in 258 serial drug tests. Sixty-nine patients were tested on phenytoin (mean serum level 13.4 +/- 5.0 mg/L), 52 after oral loading, and 17 after intravenous loading; the remaining 18 had either had prior successful testing with other drugs (9 patients) or had prior empiric failures with phenytoin (9 patients) or had prior empiric failures with phenytoin (9 patients). Nine of the 69 phenytoin trials were successful (13.0%), compared to 8 of 57 trials (14.0%) with procainamide, 4 of 37 trials (10.8%) with quinidine, and 0 of 41 trials (0%) with lidocaine. All nine patients who had successful phenytoin trials tolerated chronic doses adequate to maintain serum phenytoin levels equivalent to those measured during successful drug testing. For the 25 patients with successful drug trials, the mean follow-up was 14.5 +/- 9.8 months, and the actuarial incidence or recurrent VT/VF was 7 +/- 5% at 12 months. For the nine patients who had success with phenytoin the mean follow-up was 18.4 +/- 11.7 months, and the 12-month actuarial recurrence was 0%. Phenytoin is a well tolerated drug whose efficacy appears similar to most standard antiarrhythmic agents. If our results are confirmed in a larger, randomized study, routine testing with phenytoin should be considered.

Anti-Arrhythmia Agents

Empiric amiodarone versus "ineffective" drug therapy in patients with refractory ventricular tachyarrhythmias.

Because of its presumed unique efficacy, amiodarone (AM) is often used to treat patients whose sustained ventricular tachyarrhythmias (VT/VF) appear to be drug-refractory. To examine the efficacy of AM in such patients, we performed a retrospective analysis of 77 patients with drug-refractory VT/VF treated with either empiric AM or with drugs predicted during electrophysiological (EP) testing to be ineffective (ID). To qualify for the study, patients had to have spontaneous, symptomatic VT/VF, and persistently inducible VT during serial EP testing with drugs. All 77 patients were offered therapy with AM. Those who refused were treated with ID, whenever possible, an ID was selected which "improved" the EP study compared to baseline. Originally, 68 patients elected AM and nine elected ID. Because of drug intolerance or inefficacy, 10 patients crossed over during the course of the study; a total of 71 patients were followed on AM for 15.7 +/- 11.0 months, and 16 on ID for 17.8 +/- 10.8 months (mean +/- SD). During follow-up, the cumulative recurrence of VT/VF at 6, 12, and 24 months for AM versus ID was 16 +/- 5% versus 44 + 12% (P less than 0.002), 32 +/- 6% versus 44 +/- 12% (NS), and 41 +/- 7% versus 44 +/- 12% (NS) (+/- SE). The recurrence of VT was significantly lower in the AM group only for the first 6 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Pharmacokinetics of moricizine HCl.

Moricizine HCl is a phenothiazine derivative with antiarrhythmic properties. It was developed in the USSR and is now undergoing clinical evaluation. Although preliminary work has shown moricizine HCl to be effective in treating both atrial and ventricular arrhythmias, little is known of its pharmacokinetics. There is a 4-fold variability in range for its elimination half-life and in volumes of distribution and clearance. There is a linear relation for peak plasma levels and area under the plasma concentration/time curve with regard to single-dose administration of moricizine HCl. The bioavailability of moricizine HCl connotes extensive first-pass effect, or presystemic metabolism. Very little of moricizine is excreted unchanged; it is extensively metabolized to certain compounds that are present in plasma for extended periods. Moricizine is extensively (92% to 95%) bound to plasma protein. Its coadministration with cimetidine leads to additive systemic effects; however, there is no evidence of alterations in steady-state levels when moricizine HCl is coadministered with digoxin. Because moricizine is a drug with active metabolites, its concentration/effect profile is complex; this poses a challenge for accurate dose titration. This may, however, be a helpful challenge in that the metabolites may one day prove useful in therapy. This surmise warrants further study.

Anti-Arrhythmia Agents

Disposition of moracizine (ethmozine) in healthy subjects after oral administration of radiolabelled drug.

Moracizine (ethmozine) is a phenothiazine derivative with demonstrated antiarrhythmic activity. To characterize the pharmacokinetics and material balance relationships in humans, we have given 14C-moracizine X HCl as a single oral dose of 500 mg (50 microCi) to six healthy men. Plasma, urine, and faecal samples were collected for 7 days after administration and the concentrations of total radioactivity and intact moracizine were determined by liquid scintillation counting and HPLC, respectively. Urine and faecal recovery accounted for 95% of the administered radioactivity. Most of this radioactivity was found in the faeces (59%). Only 0.05% of the dose was recovered from urine as intact moracizine. The Cmax and AUC for moracizine equivalents of total radioactivity were 4- and 18-fold higher, respectively, than the corresponding values for intact moracizine. Additionally, both the disappearance of total radioactivity from plasma and its excretion rate into urine were slower in comparison to intact drug. Terminal t1/2 values calculated from plasma concentration-time data were 85.2 and 3.5 h for total radioactivity and intact moracizine, respectively. However, based on urinary excretion rates, the t1/2 for total radioactivity was shorter (29.3 h) while the t1/2 for intact drug was comparable (2.7 h) to the results obtained from the plasma data. The oral plasma clearance of moracizine was relatively large (2.2 l X min-1), suggesting first-pass metabolism. The estimated oral systemic availability of moracizine was 34%.

Administration, Oral

Electrocardiographically discrete right and left ventricular QRS complexes: a case report.

A patient with congestive cardiomyopathy manifested a right ventricular QRS followed after 80 msec. by a left ventricular QRS in response to a single atrial depolarization. The ventricular sequence was reversible when the left ventricle was paced directly. Virtually the entire ipsilateral ventricular ejection period occurred during diastolic filling of the contralateral ventricle. Triggered left ventricular pacing, using the right ventricular electrogram as trigger, shortened the QRSRV-QRSLV interval and resulted in a reduction of left ventricular filling pressure and a significant rise in cardiac output. These findings indicated an independent contribution of this unique form of interventricular conduction disturbance to deterioration in hemodynamic performance.

Atrial Flutter

The automatic implantable cardioverter-defibrillator in drug-refractory ventricular tachyarrhythmias.

STUDY OBJECTIVE: To assess the efficacy of the automatic implantable cardioverter-defibrillator in preventing sudden death in high-risk patients. DESIGN: Nonrandomized cohort study. SETTING: A university teaching hospital with 500 beds. PATIENTS: Consecutive sample of 78 patients with symptomatic, sustained ventricular tachyarrhythmias that were previously drug-refractory. INTERVENTIONS: Before February 1985, patients received treatment with the defibrillator and amiodarone if they presented with loss of consciousness (group A) and amiodarone alone if they did not lose consciousness (group C). After February 1985, because the availability of the defibrillator was severely curtailed, patients who lost consciousness received treatment with amiodarone alone (group B). MEASUREMENTS AND MAIN RESULTS: The risk for recurrent arrhythmias was similar between groups. The actuarial risk for sudden death in group B was 31% (95% confidence interval, 11% to 51%) at 1 and 2 years, a value that was significantly higher than that for group A (p less than 0.003) or group C (p less than 0.03). The risk for dying suddenly with the first recurrence was 0.78 in group B, a value that was significantly higher than that for group A (p less than 0.003) or group C (p less than 0.002). CONCLUSION: The defibrillator is highly effective in preventing sudden death in patients whose presenting arrhythmias caused loss of consciousness (group A). In patients whose presenting arrhythmias did not result in loss of consciousness (group C), initial treatment with the defibrillator appears unnecessary.

Aged