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Michael R Gold

Publications and source records attributed to Michael R Gold.

At least 19 recordsLinked to original sources
PubMed2007

Pacing Evaluation-Atrial SUpport Study in Cardiac Resynchronization Therapy (PEGASUS CRT): design and rationale.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been demonstrated to be an effective heart failure (HF) therapy. All pivotal trials of CRT to date have used atrial-synchronous biventricular pacing wherein there is no or minimal atrial pacing. In clinical practice, however, physicians often program CRT devices to have atrial rate support pacing, either by increasing the lower rate limit or by activating the rate sensor. OBJECTIVE: The purpose of this study is to evaluate the effect of empiric atrial support pacing in patients with HF who have received a CRT defibrillator (CRT-D) device. METHODS: PEGASUS CRT is a multicenter, 3-arm, randomized clinical trial of approximately 1200 patients receiving a CRT-D device. For the first 6 weeks after implant, devices are programmed to DDD with a lower rate limit of 40 beats/min. At 6 weeks, patients are randomized to DDD-40, DDD-70, or DDDR-40. All randomized patients are followed for 1 year, and at each visit, mortality, HF events, quality of life, New York Heart Association class, and atrial and ventricular arrhythmic episodes are evaluated. An exercise substudy will also be conducted, enrolling a minimum of 375 patients. Patients in this substudy will complete 2 cardiopulmonary exercise tests to evaluate the effect pacing mode has on exercise capacity. This randomized controlled trial will address whether empiric atrial support pacing is of clinical benefit to patients with HF who receive a CRT-D device.

Cardiac Pacing, Artificial↗
PubMed2006

Coronary sinus electrode does not reduce atrial defibrillation thresholds.

BACKGROUND: Atrial defibrillation can be achieved with a conventional dual-coil, active pectoral implantable cardioverter-defibrillator (ICD) lead system. Shocking vectors that incorporate an additional electrode in the CS have been used, but it is unclear if they improve atrial DFTs. OBJECTIVE: The objective of this prospective, randomized study was to determine if a coronary sinus (CS) electrode reduces atrial defibrillation thresholds (DFTs). METHODS: This was a prospective study of 36 patients undergoing initial ICD implant for standard indications. A defibrillation lead with superior vena cava (SVC) and right ventricular (RV) shocking coils was implanted in the RV. An active can emulator (Can) was placed in a pre-pectoral pocket. A lead with a 4 cm long shocking coil was placed in the CS. Atrial DFTs were determined in the following 3 shocking configurations in each patient, with the order of testing randomized: RV --> SVC + Can (Ventricular Triad), distal CS --> SVC + Can (Distal Atrial Triad), and proximal CS --> SVC + Can (Proximal Atrial Triad). RESULTS: The Proximal and Distal Atrial Triad configurations were both associated with significant reductions in peak current (p < 0.01), but this effect was offset by significant increases in shock impedance (p < 0.01), resulting in no net change in the peak voltage or DFT energy in comparison to the Ventricular Triad configuration (Ventricular Triad: 4.9 +/- 6.6 J, Proximal Atrial Triad: 3.3 +/- 4.1J, Distal Atrial Triad: 4.4 +/- 6.7 J, p > 0.2). CONCLUSION: Shocking vectors that incorporate a CS coil do not significantly improve atrial defibrillation efficacy. Since the Ventricular Triad shocking pathway provides reliable atrial and ventricular defibrillation, this configuration should be preferred for combined atrial and ventricular ICDs.

Atrial Fibrillation↗
PubMed2006

Selective induction of matrix metalloproteinases and tissue inhibitor of metalloproteinases in atrial and ventricular myocardium in patients with atrial fibrillation.

Atrial fibrillation (AF) produces changes in atrial structure and extracellular matrix composition, which is regulated by matrix metalloproteinases (MMPs). Moreover, AF often occurs in the setting of congestive heart failure (CHF), which also affects MMPs. Whether changes in MMPs or the tissue inhibitors of metalloproteinases (TIMPs) within atrial and ventricular myocardium are differentially regulated with AF remains unclear. Myocardium from the walls of the right atrium, right ventricle, left atrium, and left ventricle was obtained from the explanted hearts of 43 patients with end-stage CHF. AF was present in 23 patients (duration 1 to 84 months). The remaining 20 patients served as non-AF controls. The groups were well matched clinically, but left atrial (LA) size was increased in the AF cohort (5.5 +/- 0.8 vs 4.9 +/- 0.7 cm, p <0.05). Myocardial collagen content and levels of MMP-1, -2, -8, -9, -13, and -14, and TIMP-1, -2, -3, and TIMP-4 were determined. With AF, collagen content was greater within the atrial myocardium but less in the ventricular myocardium. There were chamber-specific differences in MMPs and TIMPs with AF. For example, MMP-1 in the right atrium and MMP-9 in the left atrium were greater with AF. TIMP-3 levels were greater in the right ventricle, left atrium, and left ventricle. Although total LA collagen was positively correlated with AF duration (r = 0.49, p <0.03), there was an inverse relation between soluble collagen I and AF duration (n = 6, r = -0.84, p <0.04). In conclusion, AF is associated with chamber-specific alterations in myocardial collagen content and MMP and TIMP levels, indicative of differential remodeling and altered collagen metabolism. Differences in MMP and TIMP profiles may provide diagnostic and mechanistic insights into the pathogenesis of AF with CHF.

Adult↗
PubMed2006

The Rap GTPases mediate CXCL13- and sphingosine1-phosphate-induced chemotaxis, adhesion, and Pyk2 tyrosine phosphorylation in B lymphocytes.

The localization of B cells to lymphoid organs where they can become activated and differentiate into antibody-secreting plasma cells is controlled by multiple chemoattractants that promote cell migration and integrin-mediated adhesion. CXCL13 and sphingosine 1-phosphate (S1P) are two important chemoattractants that control the trafficking of B cells. CXCL13 directs B lymphocytes to lymphoid follicles where they receive survival signals and, if activated, undergo a germinal center response. In contrast, S1P allows B cells and plasma cells to exit lymphoid organs and re-enter the circulation. The Rap1 GTPase is a key regulator of cell adhesion and cell migration in a number of systems. We now show that Rap activation is required for CXCL13 and S1P to induce B cell migration as well as adhesion to ICAM-1 and VCAM-1. We also show that Pyk2, a tyrosine kinase involved in cytoskeleton rearrangements and B cell migration, is a downstream target of both CXCL13 and S1P signaling and that Rap activation is important for CXCL13 and S1P to stimulate tyrosine phosphorylation of Pyk2, a modification that increases Pyk2 kinase activity. This suggests that the ability of CXCL13 and S1P to direct the trafficking and localization of B cells in vivo may be dependent on Rap activation.

Animals↗
PubMed2006

Rationale and design of a randomized clinical trial to assess the role of overdrive and triggered prevention pacing therapies in reducing atrial fibrillation: the Study of Atrial Fibrillation Reduction (SAFARI).

BACKGROUND: Rhythm control in selected patients diagnosed with paroxysmal atrial fibrillation (AF) remains a clinically important goal. The role of pacing therapies for maintaining that goal remains unclear, despite considerable study effort. Several pacing strategies have been evaluated to treat AF, including various prevention pacing therapies (PPTs) designed to suppress known triggers of AF. The inconsistent results and difficulty interpreting the results of past studies stems in part from variability in trial designs, patient populations, and end points. METHODS: The SAFARI is the largest, multicenter, prospective, randomized clinical trial that aims to address many of the design limitations of previous trials to delineate better the role of PPTs. The primary end point for the study is total AF burden as reported by the device. Patients are selected to include only those with paroxysmal AF and to exclude those without documented arrhythmias. A 1-month postimplant lead stabilization period followed by a 3-month run-in period is incorporated into the design to help exclude patients with no AF after implantation or patients in whom the accuracy of the device reported AF burden is suspect. A suite of 6 PPTs is used to treat multiple different triggers of arrhythmia. Data will be gathered for 10 months. Enrollment of 546 patients was completed in January 2005; patient follow-up visits are expected to be completed in November 2005. CONCLUSION: By using a study design that addresses the limitations of previous trials, SAFARI will help significantly refine our understanding of the role of pacing to prevent AF.

Atrial Fibrillation↗
PubMed2006

ASymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the atrial fibrillation Reduction atrial pacing Trial (ASSERT).

Asymptomatic atrial fibrillation (AF) is common and may have the same prognostic implications as symptomatic AF. Among patients receiving dual-chamber pacemakers, it is now possible to quantify asymptomatic AF accurately. Most of these episodes are of short duration, often lasting only seconds to minutes and are called atrial high-rate episodes (AHRE) to distinguish them from the longer episodes of overt AF. To understand properly the clinical importance of asymptomatic AF, a large study of pacemaker patients without clinically overt AF is required. ASSERT is a multicenter, cohort follow-up, and single-blinded randomized trial in elderly hypertensive patients with a pacemaker recently implanted for sinus or atrioventricular node disease. The goals of this trial are to evaluate whether the detection of AHRE with pacemaker telemetry predicts an increased risk of stroke and other vascular events and to evaluate if atrial overdrive pacing reduces symptomatic AF. ASSERT is evaluating the hypothesis that among pacemaker patients without a previous history of AF, detection of AHRE predicts an increased risk of stroke and systemic embolism. The second hypothesis to be tested is that overdrive atrial pacing will reduce the risk of symptomatic AF in pacemaker patients without a previous history of AF. Finally, a 400-patient substudy will use the noninvasive testing capabilities of the patients' pacemaker to evaluate changes in atrial electrophysiology over 2 years. This substudy will determine if atrial electrical remodeling is detectable in pacemaker patients and if it is associated with the development of AF.

Aged↗
PubMed2006

Effect of an active abdominal pulse generator on defibrillation thresholds with a dual-coil, transvenous ICD lead system.

INTRODUCTION: Many patients with implantable cardioverter defibrillators (ICDs) have older lead systems, which are usually not replaced at the time of pulse generator replacement unless a malfunction is noted. Therefore, optimization of defibrillation with these lead systems is clinically important. The objective of this prospective study was to determine if an active abdominal pulse generator (Can) affects chronic defibrillation thresholds (DFTs) with a dual-coil, transvenous ICD lead system. METHODS AND RESULTS: The study population consisted of 39 patients who presented for routine abdominal pulse generator replacement. Each patient underwent two assessments of DFT using a step-down protocol, with the order of testing randomized. The distal right ventricular (RV) coil was the anode for the first phase of the biphasic shocks. The proximal superior vena cava (SVC) coil was the cathode for the Lead Alone configuration (RV --> SVC). For the Active Can configuration, the SVC coil and Can were connected electrically as the cathode (RV --> SVC + Can). The Active Can configuration was associated with a significant decrease in shock impedance (39.5 +/- 5.8 Omega vs. 50.0 +/- 7.6 Omega, P < 0.01) and a significant increase in peak current (8.3 +/- 2.6 A vs. 7.2 +/- 2.4 A, P < 0.01). There was no significant difference in DFT energy (9.0 +/- 4.6 J vs. 9.8 +/- 5.2 J) or leading edge voltage (319 +/- 86 V vs. 315 +/- 83 V). An adequate safety margin for defibrillation (> or =10 J) was present in all patients with both shocking configurations. CONCLUSION: DFTs are similar with the Active Can and Lead Alone configurations when a dual-coil, transvenous lead is used with a left abdominal pulse generator. Since most commercially available ICDs are only available with an active can, our data support the use of an active can device with this lead system for patients who present for routine pulse generator replacement.

Abdominal Muscles↗
PubMed2006

The Rhythm ID Going Head to Head Trial (RIGHT): design of a randomized trial comparing competitive rhythm discrimination algorithms in implantable cardioverter defibrillators.

BACKGROUND: The implantable cardioverter defibrillator (ICD) has become primary therapy for the prevention of sudden death. One of the major morbidities of ICD use remains inappropriate therapy for supraventricular arrhythmias (SVA). Detection enhancements have increased therapy specificity, but their impact on inappropriate therapy is not well studied. Moreover, ICD manufacturers have developed unique algorithms to meet this goal, with no previous clinical direct comparisons. RIGHT is a randomized, prospective study that will assess the differential efficacy of ICDs from two different manufacturers. It is the first trial to compare directly competitive ICD rhythm discrimination algorithms on a large scale. OBJECTIVE: The primary objective of this study is to assess arrhythmia discrimination in Guidant versus Medtronic ICDs by comparing the time to first inappropriate therapy after the predischarge visit. METHODS: The study will enroll approximately 2,000 patients in 100 centers. Patients will be randomized to Guidant or Medtronic using a permuted block design, stratified by center and by single/dual chamber device types. Patients will receive a commercially available Guidant VITALITY 2 family ICD with Rhythm ID or a Medtronic ICD using the Enhanced PR Logic or Wavelet discrimination algorithms, and will be followed according to the schedule shown until a common closing date with a minimum follow-up of 12 months. All events will be reviewed by an independent committee to determine the appropriateness of rhythm classification and therapy delivery. CONCLUSION: RIGHT is the first randomized, large scale, head-to-head comparison of ICD discrimination algorithms.

Algorithms↗
PubMed2005

Clinical predictors of atrial defibrillation thresholds with a dual-coil, active pectoral lead system.

OBJECTIVES: The purpose of this study was to identify clinical predictors of atrial defibrillation thresholds (DFTs) with standard implantable cardioverter-defibrillator (ICD) leads. BACKGROUND: Atrial defibrillation can be achieved with active pectoral, dual-coil transvenous ICD lead systems. If clinical predictors of atrial defibrillation efficacy with these lead systems were identified, they could be used to predict which patients may require more complex lead systems for atrial defibrillation, such as a coronary sinus electrode. METHODS: This was a prospective study of 135 consecutive patients undergoing initial ICD implant for standard indications. The lead system evaluated was a transvenous defibrillation lead with coils in the superior vena cava (SVC) and right ventricular apex (RV), and a left pectoral pulse generator emulator (CAN). The shocking pathway was RV-->SVC+CAN. Atrial DFT was measured using a step-up protocol. Clinical and echocardiographic parameters were evaluated as predictors of atrial DFT and multiple linear regression was performed. RESULTS: Mean atrial DFT was 4.6 +/- 3.8 J. Atrial DFT was < or =3 J in 70 patients (52%) and < or = 10 J in 97% of patients. The highest atrial DFT was 20 J (one patient). Left atrial size (r = 0.21, P = .01) and left ventricular end-diastolic diameter (r = 0.19, P = .02) were independent predictors of atrial DFT. However, these two predictors accounted for only 6% of the variability in atrial DFT. CONCLUSIONS: Clinical parameters are of limited use in predicting atrial DFT with a dual-coil, active pectoral ICD lead system. Because the RV--> SVC + CAN shocking pathway provides reliable atrial and ventricular defibrillation, this configuration should be preferred for combined atrial and ventricular ICDs.

Atrial Fibrillation↗
PubMed2005

Improved defibrillation efficacy with an ascending ramp waveform in humans.

OBJECTIVES: The purpose of this study was to compare an ascending ramp waveform (RAMP) with a standard, clinically available biphasic truncated exponential waveform (BTE) for defibrillation in humans. BACKGROUND: In animal studies, RAMP had a lower defibrillation threshold (DFT) than BTE. METHODS: We studied 63 patients at implantable cardioverter-defibrillator placement using a dual-coil lead and left pectoral active can. The subjects were divided into two groups, one with a 12-ms ascending first phase and one with a 7-ms ascending first phase. Phase 2 of RAMP for both groups was a truncated exponential decay with 65% tilt and reversed polarity. The BTE had a 50% tilt in each phase. DFT and upper limit of vulnerability (ULV) were measured for both waveforms using a binary search protocol. RESULTS: The patient population was 77% male, with a mean age of 63 +/- 10 years and ejection fraction of 33 +/- 13%. Delivered energy at DFT was lower with the 7-ms RAMP vs BTE (5.4 +/- 2.6 J vs 6.5 +/- 3.4 J; P < .01) but unchanged with the 12-ms RAMP (7.4 +/- 4.5 J vs 7.1 +/- 4.9 J). Maximal voltage at DFT was significantly lower with either RAMP compared to BTE (P < .01). There was a strong correlation between ULV and DFT for both RAMP and BTE (P < .01). CONCLUSIONS: The 7-ms ascending ramp waveform significantly reduced delivered energy (18%) and voltage (24%) at DFT, whereas the 12-ms RAMP reduced only DFT voltage. This is the first report of a waveform that is superior to a BTE for defibrillation in humans. ULV correlates with DFT for RAMP, supporting the use of ULV testing for implantation of devices.

Algorithms↗
PubMed2005

Comparison of stimulation sites within left ventricular veins on the acute hemodynamic effects of cardiac resynchronization therapy.

OBJECTIVES: The purpose of this study was to study the acute hemodynamic effect of left ventricular (LV) stimulation sites within a coronary vein. BACKGROUND: Access to LV stimulation sites for resynchronization therapy is achieved using specialized lead systems navigated through a coronary vein. The effects of stimulation in different coronary veins have been evaluated previously, but less is known about stimulation sites within a coronary vein. METHODS: Twenty-four patients (New York Heart Association functional class II-IV, age 59 +/- 10 years, ejection fraction 21 +/- 7%, QRS 166 +/- 30 ms) were enrolled in the study. A novel over-the-wire lead system was used to access an anterior or lateral coronary vein. At each lead location, a randomized stimulation protocol was executed. Hemodynamic responses were evaluated using LV dP/dtmax. RESULTS: The mean time to cannulate the coronary sinus and position the LV lead was 19 +/- 30 minutes and 17 +/- 18 minutes, respectively. Data from stimulation at two sites within a coronary vein were obtained in 19 patients (anterior vein 11; lateral vein 8). Of these patients, 14 (anterior vein 9; lateral vein 5) showed large improvement in dP/dtmax (22%-25% in anterior vein, 37%-40% in lateral vein). Overall, there were no group differences in hemodynamic effects among different stimulation sites within a coronary vein, although significant variability among sites was observed in individuals. CONCLUSIONS: Resynchronization therapy through a coronary vein improves acute hemodynamic function of heart failure patients with LV conduction disorder. There were no significant differences between basal and apical pacing sites for this group.

Aged↗
PubMed2005

Sustained ventricular tachycardia following alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

A 49-year-old man with a history of hypertrophic obstructive cardiomyopathy (HOCM) presented in sustained monomorphic ventricular tachycardia (SMVT) 8 days post-alcohol septal ablation. A dual chamber implantable cardioverter defibrillator ICD was implanted and the patient experienced another episode of VT 3 weeks later, which was terminated by an ICD shock. This case demonstrates probable scar-induced reentrant VT post-alcohol septal ablation, a likely rare but hypothesized complication of this procedure.

Cardiomyopathy, Hypertrophic↗
PubMed2004

Efficacy of transthoracic cardioversion of atrial fibrillation using a biphasic, truncated exponential shock waveform at variable initial shock energies.

Biphasic shocks are more effective than damped sine wave monophasic shocks for transthoracic cardioversion (CV) of atrial fibrillation (AF), but the optimal protocol for CV with biphasic shocks has not been defined. We conducted a prospective, randomized study of 120 consecutive patients with persistent AF to delineate the dose-response curve for CV of AF with a biphasic truncated exponential shock waveform and to identify clinical predictors of shock efficacy. Our data suggest that the initial shock energy for CV with this waveform should be 200 J if the patient weighs <90 kg and 360 J if the patient weighs >/=90 kg.

Aged↗