Search PubMed⌕ Search

Biomedical subjects

M R Gold

Publications and source records attributed to M R Gold.

At least 91 records · Page 5Linked to original sources
PubMed1997

Gender differences in presentation, management, and cardiac event-free survival in patients with syncope.

In a MEDLINE search of published English studies (1966 to 1996), no prior study was identified that examined gender-based differences in the management and prognosis of patients admitted with syncope. We studied 109 consecutive patients (48 women) admitted with syncope at the Massachusetts General Hospital (1989 to 1990). All patients underwent Holter monitoring, signal-averaged electrocardiography, and echocardiography according to study protocol. Follow-up was 100% complete (10 +/- 4 months). Women were older (74 +/- 2 vs 66 +/- 2 years, p <0.01) and less likely to have premonitory symptoms when compared with men (46% vs 66%, p <0.05). A greater proportion of men had left ventricular ejection fractions of <0.40 (18% vs 0%, p <0.01), abnormal signal-averaged electrocardiograms (28% vs 8%, p <0.01), and a cardiac cause for syncope (49% vs 25%, p <0.01). Although referral for diagnostic electrophysiologic testing was >3 times as frequent for men compared with women (20% of men vs 6% of women, p <0.05), this difference was not significant after adjustment for age, ventricular arrhythmia, and referral for coronary angiography. During follow-up, 21% of men versus 6% of women (p <0.05) had cardiac events (recurrent syncope, myocardial infarction, or sudden death). Cardiac event-free survival rates were worse for men (p = 0.045). Thus, we have identified gender-based differences in the clinical presentation of syncope for hospital admission. Left ventricular dysfunction and an abnormal signal-averaged electrocardiogram occur more frequently in men. Men are more likely to have cardiac syncope and worse cardiac event-free survival when compared with women.

Aged↗
PubMed1997

Effect of biphasic waveforms on transvenous defibrillation thresholds in patients with coronary artery disease.

This study is a prospective, randomized comparison of monophasic and biphasic defibrillation thresholds in 19 patients with a single transvenous lead. Despite using reverse polarity and optimal tilts for the monophasic waveform, the defibrillation threshold was reduced with biphasic shocks from 15.8 +/- 11.3 to 11.5 +/- 6.1 (p <0.05) with comparable reductions of leading edge voltage and current.

Aged↗
PubMed1997

Induction of atrial fibrillation with low-energy defibrillator shocks in patients with implantable cardioverter defibrillators.

In a population of 151 consecutive patients who received an implantable cardioverter defibrillator, we found that atrial fibrillation was induced by low-energy shocks in 19% and was most common in patients with lead systems that included a right atrial electrode. Our finding that there was a fixed relation between the energy required to fibrillate (< or = 3 J) and defibrillate (> 3 J) suggests the presence of an upper limit of vulnerability in the human atrium.

Aged↗
PubMed1997

Comparison of class Ia/Ib versus class III antiarrhythmic drugs for the suppression of inducible sustained ventricular tachycardia associated with coronary artery disease.

Previous studies suggest that class Ia drugs are ineffective in suppression of sustained ventricular tachycardia by programmed stimulation. More favorable results have been described with combinations of Ia and Ib drugs and also with class III antiarrhythmic drugs, but there have been no direct comparisons between these 2 regimens. The present study was undertaken to compare the electrophysiologic efficacy and predictors of success of these 2 regimens in patients with ischemic heart disease and inducible sustained monomorphic ventricular tachycardia. The population consisted of 136 patients with documented coronary artery disease. All had sustained monomorphic ventricular tachycardia inducible during baseline electrophysiologic study and following intravenous procainamide. Follow-up studies were performed with a combination of oral class Ia and Ib or class III antiarrhythmic drugs. A positive response was the inability to induce a sustained ventricular arrhythmia with up to 3 extrastimuli at 2 right ventricular pacing sites. Response rates were 13% for Ia/Ib combination and 19% for class III agents (p = 0.40). Congestive heart failure differentially affected response rates. Only 8% of those responding to Ia/Ib therapy had heart failure compared with 59% of responders to class III (p <0.01). Multivariate analysis identified heart failure (RR 12.2, p = 0.03) as the only parameter with independent predictive value of response to Ia/Ib therapy. These results indicate that congestive heart failure is a potent predictor of a negative response to a combination of class Ia and Ib antiarrhythmic drugs. In this population, class III drugs or nonpharmacologic therapy should be considered as initial treatment.

Aged↗
PubMed1997

Clinical predictors of transvenous biphasic defibrillation thresholds.

Transvenous lead systems have become routine for defibrillator placement. However, previous studies of clinical predictors of an adequate nonthoracotomy defibrillation threshold (DFT) evaluated monophasic waveforms or more complex lead systems, including subcutaneous patches. Accordingly, this study is a prospective evaluation of the predictors of an adequate biphasic DFT in 114 consecutive patients undergoing cardioverter-defibrillator implantation with a single transvenous lead. For each subject, 38 parameters were assessed, including standard demographic, electrocardiographic, echocardiographic, and radiographic measurements. An adequate DFT (< or =20 J) was achieved in 92% of patients. Multivariable analysis revealed 2 independent factors predictive of a high threshold: echocardiographic measurements of left ventricular dilation (odds ratio = 0.16, 95% confidence interval 0.05 to 0.53, p = 0.003) and body size (odds ratio = 0.36, 95% confidence interval 0.17 to 0.73; p = 0.005). No patient with a normal left ventricular end-diastolic dimension had a high DFT, whereas 14% (9 of 66) of those with left ventricular dilation had elevated thresholds. When the DFT cutoff was lowered to 15 J, as is necessary with some downsized pulse generators, an adequate threshold was observed in 84% of patients and the same 2 independent predictors of high thresholds were found. These results indicate that an adequate transvenous DFT can be predicted from simple clinical parameters.

Aged↗
PubMed1997

The acute hemodynamic effects of right ventricular septal pacing in patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

To assess the hemodynamic effects of right ventricular septal pacing in patients with severe chronic heart failure, we studied 13 patients during intrinsic rhythm and with pacing in the VDD mode at atrioventricular delays of 100 to 200 ms. There was no improvement of any hemodynamic parameter measured with pacing, even in the subgroup of patients with prolonged PR intervals.

Atrioventricular Node↗
PubMed1997

Chronic rise in monophasic defibrillation thresholds with a transvenous lead system.

This study was a prospective evaluation of chronic changes of defibrillation thresholds in 31 clinically stable patients with a single transvenous lead, optimal shock polarity, and uniform testing protocol. At a mean follow-up of 273 +/- 146 days, defibrillation thresholds increased 26%, from 13.2 +/- 5.6 J to 17.1 +/- 6:0 J (p < 0.001), and shock impedance increased from 46.2 +/- 7.0 omega to 51.2 +/- 6.2 omega (p < 0.001).

Aged↗
PubMed1997

Clinical predictors of transvenous defibrillation energy requirements.

Nonthoracotomy and, more recently, transvenous lead systems have become routine for initial implantable cardioverter-defibrillator (ICD) placement. Previous studies of clinical predictors of nonthoracotomy defibrillation energy requirements evaluated multiple complex lead systems that included subcutaneous patches. However, the predictors of an adequate transvenous defibrillation threshold (DFT) have not been assessed previously. Accordingly, the present study is a prospective evaluation of DFT using a uniform testing protocol in 119 consecutive patients undergoing ICD implantation with a single transvenous lead. For each patient, 38 parameters were assessed including standard clinical, echocardiographic, and radiographic measures. An adequate monophasic DFT (< or =20 J) was achieved in 76% of patients. Multivariable analysis revealed 3 independent factors predictive of a high threshold: preoperative amiodarone use (odds ratio = 5.8, p < or =0.002), echocardiographic measures of left ventricular dilation (odds ratio = 0.47, p < or =0.005) and body size (odds ratio = 0.51, p < or =0.006). Patients receiving amiodarone who also had left ventricular dilation constitute a group at considerable (69%) risk for having a high DFT. In contrast, patients with neither of these risk factors have only an 11% chance of having a high threshold. We conclude that an adequate transvenous DFT can be predicted from simple clinical parameters.

Amiodarone↗
PubMed1997

Biphasic waveforms prevent the chronic rise of defibrillation thresholds with a transvenous lead system.

OBJECTIVES: The purpose of this study was to compare chronic changes in monophasic and biphasic defibrillation thresholds using a uniform transvenous lead system and testing protocol. BACKGROUND: Defibrillation thresholds increase over time in patients with nonthoracotomy lead systems. This increase can result in an inadequate chronic defibrillation safety margin and could limit the safety of smaller pulse generators, which have a reduced maximal output. However, previous studies of the temporal changes of defibrillation thresholds evaluated complex lead systems or monophasic shock waveforms, neither of which are used with current technology. METHODS: This study was a prospective, randomized assessment of the effects of shock waveforms on the changes of transvenous defibrillation thresholds over time. Paired monophasic and biphasic thresholds were measured both at implantation and at follow-up (250 +/- 105 days) in 24 consecutive patients who were not receiving antiarrhythmic drugs. The lead system was a dual-coil Endotak C lead, and reverse polarity shocks (distal coil = anode) were delivered. RESULTS: Monophasic defibrillation thresholds increased from (mean +/- SD) 13.7 +/- 6.0 J to 16.8 +/- 6.7 J (p = 0.02), whereas biphasic thresholds were unchanged (10.4 +/- 4.3 J to 10.2 +/- 4.8 J, p = 0.86) in the same patients. Shock impedance chronically increased (47.0 omega to 50.5 omega, p = 0.02) and was unaffected by waveform. CONCLUSIONS: These results indicate that biphasic shocks prevent the chronic increase in defibrillation thresholds with a transvenous lead system.

Atrial Fibrillation↗
PubMed1997

Distortion of intracardiac electrograms following defibrillator shocks for atrial tachyarrhythmias.

In three patients with a defibrillator system consisting of a Ventak P2 pulse generator and an Endotak C transvenous lead, we observed distortion of intracardiac electrograms following defibrillator shocks for atrial arrhythmias. There was a transient marked widening of the intracardiac ventricular complexes resembling ventricular tachycardia. This phenomenon should be recognized when evaluating arrhythmic episodes.

Adult↗
PubMed1997

Permanent pacing from the coronary sinus in a patient with an implantable defibrillator.

A woman with an ICD underwent permanent pacemaker implantation for bradycardia-tachycardia syndrome. Despite multiple right atrial positions, oversensing secondary to "double counting" was always noted. A coronary sinus pacing catheter was inserted and left atrial pacing was accomplished with acceptable pacing and sensing characteristics. The patient has since done well without further shocks.

Bradycardia↗
PubMed1997

Complications associated with pectoral implantation of cardioverter defibrillators. World-Wide Jewel Investigators.

Pectoral placement of ICD pulse generators is now routine after downsizing of these devices. However, the safety of this approach is not well documented. The aim of this study was to evaluate complications in a large cohort of patients undergoing initial pectoral ICD implantation. The subjects for this study were 1,000 consecutive patients receiving a Medtronic Jewel ICD at 93 centers worldwide. Cumulative follow-up for all patients was 634 patient-years, with 64.9% of patients followed for 6 months or longer. The complications evaluated were erosion, pocket hematoma, seroma, wound infection, dehiscence, device migration, lead fracture, and dislodgment. In this series, 1.8% of patients experienced a pocket complication with only 3 (0.3%) erosions and 2 (0.2%) infections. Lead complications were observed in 2.1% of subjects, most commonly early dislodgment of the RV lead. We conclude that pectoral implantation of a downsized ICD system can be performed with a low rate of complications. However, careful attention to anchoring techniques and close early monitoring is important given the 1.7% rate of lead dislodgment that occurred primarily during the first month following implantation.

Cohort Studies↗
PubMed1997

Effect of waveform tilt on defibrillation thresholds in humans.

INTRODUCTION: Despite the common use of the implantable cardioverter defibrillator to treat patients with life-threatening ventricular arrhythmias, the mechanism of defibrillation and the optimal waveform for implanted devices are poorly understood. All of the currently available pulse generators deliver exponentially declining pulses that are either automatically or manually truncated to achieve tilts of about 50% to 65%. Although this value was chosen based on experimental animal data, several theoretical models have been developed to describe defibrillation, which raise into question this choice of waveform shape. Accordingly, the present study was designed to test the effect of waveform tilt on defibrillation efficacy in humans. METHODS AND RESULTS: Twenty-three patients undergoing cardioverter defibrillator implantation were studied. Monophasic defibrillation thresholds (DFTs) were measured using a single reversal protocol at 35%, 50%, 65%, and 80% tilts by altering the pulse width of the shock. Mean defibrillation impedance was 41 +/- 6 omega. The DFT, measured by either leading-edge voltage or stored energy, was insensitive to altering the waveform tilt from 50% to 80%, only increasing when the tilt was reduced to 35%. A tilt of 65% yielded the lowest DFT voltage in only 8 of 23 patients. Significantly lower DFTs (> or = 40 V) were obtained using other tilts in seven patients. When the relationship between average current and pulse width was fit with a Weiss-Lapicque model, the data yielded a mean chronaxie of 4.6 +/- 3.0 msec and a rheobase of 4.2 +/- 1.7 A, but considerable patient variability was observed. CONCLUSION: On average, DFTs in humans are insensitive to altering monophasic waveform tilts between 50% and 80%. There is, however, considerable patient variability, raising into question the premise that a single defibrillator waveform tilt is best for all patients.

Aged↗
PubMed1997

Modulation of Na+ current inactivation by stimulation of protein kinase C in cardiac cells.

Modulation of the inward Na+ current (I(Na)) by protein kinase C (PKC) was investigated by intracellular perfusion of a peptide corresponding to the catalytic subunit of PKC (PKCP). The effects of PKC activation independent of membrane-receptor pathways were studied in neonatal rat ventricular myocytes using whole-cell patch-clamp techniques. Perfusion with 2 nmol/L PKCP caused a depolarizing shift in steady state half-inactivation relative to control (-83.2+/-1.3 versus -74.9+/-1.6 mV for control versus PKCP, respectively) without a change in current-voltage relationships or peak I(Na). The development of resting inactivation was slowed by PKCP (tau, 69.1+/-7.6 [control] versus 100.4+/-5.1 ms). Open-channel inactivation, estimated by measuring I(Na) decay from peak current at test voltages between -10 and +30 mV was significantly slowed by PKCP. Recovery from inactivation was more rapid during PKCP perfusion, with a shortening of both the fast (tau(f)) and slow (tau(s)) components of tau (tau(f), 38.5+/-7.0 [control] versus 14.2+/-4.7 ms; tau(s), 163.4+/-47.9 [control] versus 51.3+/-9.2 ms). All of the effects of PKCP on I(Na) were antagonized by the PKC inhibitors chelerythrine chloride or staurosporine or by down-regulation of PKC using phorbol ester preincubation. We conclude that the actions of PKC on the Na+ channel result in slowing the development of inactivation and accelerating reactivation, resulting in less resting inactivation.

Alkaloids↗
PubMed1997

Lysophosphatidylcholine modulates cardiac I(Na) via multiple protein kinase pathways.

Lysophosphatidylcholine (LPC) is a naturally occurring intracellular phospholipid metabolite that has been implicated in arrhythmogenesis during ischemia. LPC has been shown to affect the cardiac Na+ current (I(Na)), but the mechanism of modulation remains undescribed. Recently, low concentrations of LPC have been shown to activate protein kinase C (PKC) independent of the receptor-delineated pathway. The purposes of this study were to describe the effects of intracellularly introduced LPC on I(Na) and to determine if these effects were mediated by kinases. Modulation of I(Na) was studied in ventricular cells with LPC (1 nmol/L to 1 micromol/L) internally applied using whole-cell patch-clamp techniques. Intracellular LPC caused a dose-dependent depolarizing shift of steady state inactivation that was accompanied by a change in slope factor. The development of resting inactivation from closed states was delayed 40%, whereas the recovery from inactivation was significantly accelerated. These results were mimicked by another bioactive lipid, lysophosphatidylethanolamine, or by a peptide analogue of PKC, which is a potent stimulator of endogenous PKC activity. Maximal recruitable current was significantly increased by LPC but not by PKC activation. Some of the effects of LPC on I(Na) could be partially inhibited by the specific PKC inhibitor chelerythrine chloride or by downregulation of PKC with phorbol ester pretreatment. However, genistein, a specific tyrosine kinase inhibitor, completely inhibited all the modulation of I(Na) caused by LPC. These data suggest that LPC modulates I(Na) in cardiac myocytes by a pathway that involves both PKC-dependent and tyrosine kinase- dependent phosphorylation.

Animals↗
PubMed1997

Guidelines for pharmacoeconomic studies. Recommendations from the panel on cost effectiveness in health and medicine. Panel on cost Effectiveness in Health and Medicine.

This article reports the recommendations of the Panel on Cost Effectiveness in Health and Medicine, sponsored by the US Public Health Service, on standardised methods for conducting cost-effectiveness analyses. Although not expressly directed at analyses of pharmaceutical agents, the Panel's recommendations are relevant to pharmacoeconomic studies. The Panel outlines a 'Reference Case' set of methodological practices to improve quality and comparability of analyses. Designed for studies that inform resource-allocation decisions, the Reference Case includes recommendations for study framing and scope, components of the numerator and denominator of cost-effectiveness ratios, discounting, handling uncertainty and reporting. The Reference Case analysis is conducted from the societal perspective, and includes all effects of interventions on resource use and health. Resource use includes 'time' resources, such as for caregiving or undergoing an intervention. The quality-adjusted life-year (QALY) is the common measure of health effect across Reference Case studies. Although the Panel does not endorse a measure for obtaining quality-of-life weights, several recommendations address the QALY. The Panel recommends a 3% discount rate for costs and health effects. Pharmacoeconomic studies have burgeoned in recent years. The Reference Case analysis will improve study quality and usability, and permit comparison of pharmaceuticals with other health interventions.

Cost-Benefit Analysis↗