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Biomedical subjects

Roger A Freedman

Publications and source records attributed to Roger A Freedman.

13 recordsLinked to original sources
PubMed2006

The effects of rate and irregularity on sympathetic nerve activity in human subjects.

BACKGROUND: We have recently shown that atrial fibrillation is associated with an increase in sympathetic nerve activity (SNA) compared with sinus rhythm. It remains unclear, however, whether these findings are true at various rates and whether the magnitude of sympathoexcitation is related to the degree of irregularity. OBJECTIVE: To determine the role of irregularity in mediating the SNA changes at various pacing rates. Univariate analysis showed that as the irregularity increased, SBP increased (r = 0.44, P < .001) but that MAP and DBP did not change significantly. METHODS: Using custom-made software, atrioventricular sequential pacing with predetermined rates (100, 120, and 140 bpm) and irregularities (standard deviation = 0%, 5%, 15%, and 25% of mean cycle length) was performed in 23 patients referred for electrophysiologic evaluation. Pacing at each rate/irregularity was performed for 2 minutes, with 2 minutes of recovery in between. Systolic, diastolic, and mean arterial blood pressure (SBP, DBP, and MAP), central venous pressure (CVP), and SNA were measured at baseline and during pacing. RESULTS: Univariate analysis showed that as the irregularity increased, SBP increased (r = 0.44, P < .001 but that MAP and DBP did not change significantly. A significant correlation was found between the pacing irregularity and SNA, with greater sympathoexcitation noted at greater degrees of irregularity (r = 0.2, P = .04). A five-variable linear model using DBP, MAP, CVP, and degree of pacing irregularity to predict SNA was highly statistically significant (r = 0.46, P < .001). After controlling for hemodynamic changes, for every 1% increase in irregularity, there was a 6.1% increase in SNA. CONCLUSION: We have shown that greater degrees of irregularity cause greater sympathoexcitation and that the effects of irregular pacing on SNA are independent of the hemodynamic changes.

Atrial Fibrillation↗
PubMed2006

Klebsiella pneumoniae: a rare cause of device-associated endocarditis.

Intravascular infections involving implanted pacemakers and defibrillators are being seen with increasing frequency. This report describes a case of intravascular infection of an implanted defibrillator with Klebsiella pneumoniae, an unusual pathogen for pacemaker or defibrillator infection.

Endocarditis, Bacterial↗
PubMed2006

Atrioventricular junction ablation followed by resynchronization therapy in patients with congestive heart failure and atrial fibrillation (AVERT-AF) study design.

Atrial fibrillation (AF) and congestive heart failure (CHF) affect millions of patients in the United States. Several studies suggest that AF and in particular the irregular ventricular response might be contributing to the left ventricular dysfunction. Studies that compared pharmacologic rate control to atrioventricular junction (AVJ) ablation followed by right ventricular pacing which restores a regular ventricular response, failed to show an improvement when compared to pharmacological rare control. These results might be explained by the fact that while AVJ ablation restored a regular ventricular response, it subjected patients to the detrimental effects of RV apical pacing. The AVERT-AF trial (Atrio-VEntricular Junction Ablation Followed by Resynchronization Therapy in patients with CHF and AF) is a prospective, randomized, double-blinded, multicenter trial that will be testing the hypothesis that AVJ ablation followed by biventricular pacing significantly improves exercise capacity and functional status compared to pharmacologic rate control in patients with chronic AF and depressed ejection fraction, regardless of rate or QRS duration. A total of 180 patients will be enrolled to test the primary endpoint, which is exercise duration. Patients_enrollment will begin in summer 2006 and is expected to be completed in 2008. The results of this trial should help define the best treatment option for this common arrhythmia in patients with left ventricular dysfunction.

Atrial Fibrillation↗
PubMed2006

The magnitude of sinus cycle length change during ventricular tachycardia is predictive of successful antitachycardia pacing.

BACKGROUND: Despite the wide use of antitachycardia pacing (ATP) in patients with implantable cardioverter defibrillators (ICDs), predictors of ATP success remain poorly understood. We hypothesize that the degree of sympathoexcitation, as measured by the sinus cycle length (SCL) shortening during ventricular tachycardia (VT), is a predictor of ATP success. METHODS AND RESULTS: The charts of 462 patients with dual-chamber ICDs were reviewed. A total of 88 events in 26 patients met the inclusion criteria and were analyzed. The mean SCL during the 4 seconds preceding the VT onset (SCL-baseline), and during the 4 seconds prior to ATP delivery (SCL-VT) was measured. The percent shortening in SCL was calculated as ((SCL-baseline) - (SCL-VT))/(SCL-baseline) x 100. Patients were classified into the ATP-success and ATP-failure groups depending on the VT(s) response to ATP. Using a t-test analogue for clustered data, patients in the ATP-success group exhibited a greater shortening in SCL when compared with the ATP-Failure group (5.8% compared to 4.7%, P = 0.007). The successful ATP events displayed an average SCL shortening of 6.0% compared to 1.8% in the unsuccessful ATP events (P = 0.029). When the events were analyzed, the sensitivity and specificity of a shortening in SCL of >10% in predicting ATP success were 0.29 and 1. CONCLUSION: We have shown that the SCL change during VT, a marker of the autonomic changes that accompany a tachycardia, is useful in predicting ATP success. Our findings suggest that analysis of the SCL during VT might play a role in future programming of ATP in patients with ICDs.

Cardiac Pacing, Artificial↗
PubMed2003

Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction.

BACKGROUND: Dual-chamber (DDDR) pacing preserves AV synchrony and may reduce heart failure (HF) and atrial fibrillation (AF) compared with ventricular (VVIR) pacing in sinus node dysfunction (SND). However, DDDR pacing often results in prolonged QRS durations (QRSd) as the result of right ventricular stimulation, and ventricular desynchronization may result. The effect of pacing-induced ventricular desynchronization in patients with normal baseline QRSd is unknown. METHODS AND RESULTS: Baseline QRSd was obtained from 12-lead ECGs before pacemaker implantation in MOST, a 2010-patient, 6-year, randomized trial of DDDR versus VVIR pacing in SND. Cumulative percent ventricular paced (Cum%VP) was determined from stored pacemaker data. Baseline QRSd <120 ms was observed in 1339 patients (707 DDDR, 632 VVIR). Cum%VP was greater in DDDR versus VVIR (90% versus 58%, P=0.001). Cox models demonstrated that the time-dependent covariate Cum%VP was a strong predictor of HF hospitalization in DDDR (hazard ratio [HR], 2.99 [95% CI, 1.15 to 7.75] for Cum%VP >40%) and VVIR (HR 2.56 [95% CI, 1.48 to 4.43] for Cum%VP >80%). The risk of AF increased linearly with Cum%VP from 0% to 85% in both groups (DDDR, HR 1.36 [95% CI, 1.09, 1.69]; VVIR, HR 1.21 [95% CI 1.02, 1.43], for each 25% increase in Cum%VP). Model results were unaffected by adjustment for known baseline predictors of HF hospitalization and AF. CONCLUSIONS: Ventricular desynchronization imposed by ventricular pacing even when AV synchrony is preserved increases the risk of HF hospitalization and AF in SND with normal baseline QRSd.

Aged↗
PubMed2002

Ventricular pacing or dual-chamber pacing for sinus-node dysfunction.

BACKGROUND: Dual-chamber (atrioventricular) and single-chamber (ventricular) pacing are alternative treatment approaches for sinus-node dysfunction that causes clinically significant bradycardia. However, it is unknown which type of pacing results in the better outcome. METHODS: We randomly assigned a total of 2010 patients with sinus-node dysfunction to dual-chamber pacing (1014 patients) or ventricular pacing (996 patients) and followed them for a median of 33.1 months. The primary end point was death from any cause or nonfatal stroke. Secondary end points included the composite of death, stroke, or hospitalization for heart failure; atrial fibrillation; heart-failure score; the pacemaker syndrome; and the quality of life. RESULTS: The incidence of the primary end point did not differ significantly between the dual-chamber group (21.5 percent) and the ventricular-paced group (23.0 percent, P=0.48). In patients assigned to dual-chamber pacing, the risk of atrial fibrillation was lower (hazard ratio, 0.79; 95 percent confidence interval, 0.66 to 0.94; P=0.008), and heart-failure scores were better (P<0.001). The differences in the rates of hospitalization for heart failure and of death, stroke, or hospitalization for heart failure were not significant in unadjusted analyses but became marginally significant in adjusted analyses. Dual-chamber pacing resulted in a small but measurable increase in the quality of life, as compared with ventricular pacing. CONCLUSIONS: In sinus-node dysfunction, dual-chamber pacing does not improve stroke-free survival, as compared with ventricular pacing. However, dual-chamber pacing reduces the risk of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly improves the quality of life. Overall, dual-chamber pacing offers significant improvement as compared with ventricular pacing.

Aged↗
PubMed2002

Ventricular tachycardia in structurally normal hearts.

This review focuses on four distinct syndromes of ventricular tachycardia that occur in the structurally normal heart. Recent advances in the fields of molecular biology and genetics, along with intracardiac mapping techniques, have led to a greater understanding of the underlying mechanisms of and therapeutic options for these syndromes. The cyclic AMP-mediated triggered activity tachycardias, including exercise-induced right ventricular outflow track tachycardia and repetitive monomorphic ventricular tachycardia, are the most common of these syndromes. Idiopathic left ventricular tachycardia, for which there is significant evidence for re-entry within the Purkinje network, is largely curable with catheter ablation. The long QT syndrome comprises a heterogeneous group of ion channel defects leading to prolongation of myocyte repolarization and Torsade de Pointes ventricular tachycardia. Brugada syndrome, a familial disorder of transmembrane ion transport, is felt to be the result of a group of sodium channel defects leading to characteristic electrocardiographic abnormalities, and syncope and sudden death. Primary focus is given to recent advances in our understanding of the underlying mechanism and current therapeutic approaches.

Body Surface Potential Mapping↗
PubMed2002

The Low Energy Safety Study (LESS): rationale, design, patient characteristics, and device utilization.

BACKGROUND: A 10-J energy safety margin has traditionally been used in programming implantable cardioverter defibrillators (ICDs). The Low Energy Safety Study (LESS) tests the hypothesis that programming shocks to lower energy margins is safe and effective. METHODS: Patients with standard ICD indications undergo defibrillation threshold testing (DFT) at the time of ICD implant, with reconfirmation of lowest successful energy twice (DFT++). Patients are randomized to 2 groups: the first has the initial 2 shocks for ventricular fibrillation conversion programmed at 2 energy steps above DFT++ (typically 4-6 J, maximum 10 J) with subsequent shocks at maximum energy, and the second has all shocks programmed at maximum energy. Patients are followed up every 3 months for 2 years to assess shock conversion efficacy of spontaneous arrhythmias. In a subgroup of patients, there is a second randomization to energy levels of 0, 1, 2, 3, or 4 steps above implant DFT++ for conversion testing of 3 induced ventricular fibrillation episodes at prehospital discharge, 3 months, and 12 months after implant. RESULTS: Enrollment is complete (702 patients), but follow-up results are pending. There were no significant variations in implant indications and baseline antiarrhythmic drug use over the 3-year enrollment period, although an increase in the percentage of dual-chamber ICDs implanted occurred, with the majority (65%) of implanted ICDs being dual-chamber devices by the end of the enrollment period. CONCLUSION: The results of LESS should facilitate the development of algorithms for programming ICD energy safety margins.

Aged↗