Heart rate turbulence parameters correlate with post-premature ventricular contraction changes in muscle sympathetic activity.

BACKGROUND: Heart rate turbulence (HRT) has been shown to be vagally mediated with a strong correlation to baroreflex indices. However, the relationship between HRT and peripheral sympathetic nerve activity (SNA) after a premature ventricular contraction (PVC) remains unclear. OBJECTIVE: We sought to evaluate the relationship between HRT and the changes in peripheral SNA after PVCs. METHODS: We recorded postganglionic muscle SNA during electrocardiogram monitoring in eight patients with spontaneous PVCs. Fifty-two PVCs were observed and analyzed for turbulence onset (TO) and slope (TS). SNA was quantified during (1) the dominant burst after the PVC (dominant burst area) and (2) the 10 seconds after the dominant burst (postburst SNA). RESULTS: The mean TO was 0.1% +/- 4.6%, and the mean TS was 6.1 +/- 6.6. The dominant burst area negatively correlated with TO (r = -0.50, P = .0002). The postburst SNA showed a significant positive correlation with TO (r = 0.44, P = .001) and a negative correlation with TS (r = -0.42, P = .002). These correlations remained significant after controlling for either the PVC coupling interval or the left ventricular ejection fraction. CONCLUSIONS: Our findings highlight the relationship between perturbations in HRT and pathology in the sympathetic limb of the autonomic nervous system. Future studies are needed to evaluate the prognostic role of baroreflex control of sympathetic activity in patients with structural heart disease.

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.

Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study.

BACKGROUND: The AFFIRM Study showed that treatment of patients with atrial fibrillation and a high risk for stroke or death with a rhythm-control strategy offered no survival advantage over a rate-control strategy in an intention-to-treat analysis. This article reports an "on-treatment" analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time. METHODS AND RESULTS: Modeling techniques were used to determine the relationships among survival, baseline clinical variables, and time-dependent variables. The following baseline variables were significantly associated with an increased risk of death: increasing age, coronary artery disease, congestive heart failure, diabetes, stroke or transient ischemic attack, smoking, left ventricular dysfunction, and mitral regurgitation. Among the time-dependent variables, the presence of sinus rhythm (SR) was associated with a lower risk of death, as was warfarin use. Antiarrhythmic drugs (AADs) were associated with increased mortality only after adjustment for the presence of SR. Consistent with the original intention-to-treat analysis, AADs were no longer associated with mortality when SR was removed from the model. CONCLUSIONS: Warfarin use improves survival. SR is either an important determinant of survival or a marker for other factors associated with survival that were not recorded, determined, or included in the survival model. Currently available AADs are not associated with improved survival, which suggests that any beneficial antiarrhythmic effects of AADs are offset by their adverse effects. If an effective method for maintaining SR with fewer adverse effects were available, it might be beneficial.

A comparison of the AVID and DAVID trials of implantable defibrillators.

We compared 2 studies of implantable cardiac defibrillators (ICDs) to determine the effects of device mode on outcomes. The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial (1993 to 1997) demonstrated improved survival with the ICD compared with antiarrhythmic drug therapy. The Dual-chamber And VVI Implantable Defibrillator (DAVID) trial (2000 to 2002) showed that VVI pacing at 40 beats/min in patients with ICDs reduced the combined end point of death and hospitalization for congestive heart failure compared with DDDR pacing at 70 beats/min. Patients in the AVID trial (631 of 1,016) and the DAVID trial (221 of 506) meeting common inclusion and all exclusion criteria were studied. The major end points were the time to death, and the composite end point of time to death or hospitalization for congestive heart failure. Patients in the AVID and DAVID trials were similar, but more AVID patients had coronary artery disease (p = 0.04), history of myocardial infarction (p = 0.005), and previous ventricular arrhythmias (p = 0.03). DAVID patients underwent more previous revascularization procedures (coronary artery bypass surgery, p = 0.03; percutaneous coronary intervention, p = 0.001), and were more often taking beta-blocking drugs at hospital discharge (p <0.001). The backup VVI ICD groups in both studies had similar outcomes (p = 0.4), even when corrected for the previous demographic differences. The time-to- composite end point was similar in AVID patients treated with antiarrhythmic drugs and DAVID patients treated with DDDR ICDs (p = 0.6). Despite improved pharmacologic therapy and revascularization, outcomes have not improved with backup VVI pacing ICDs. If DDDR ICDs had been used in the AVID trial, benefit from ICDs for patients with serious ventricular arrhythmias could have been missed.

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.

Comparison of arrhythmia recurrence in patients presenting with ventricular fibrillation versus ventricular tachycardia in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial.

Because many episodes of ventricular fibrillation (VF) are believed to be triggered by ventricular tachycardia (VT), patients who present with VT or VF are usually grouped together in discussions of natural history and treatment. However, there are significant differences in the clinical profiles of these 2 patient groups, and some studies have suggested differences in their response to therapy. We examined arrhythmias occurring spontaneously in 449 patients assigned to implantable cardioverter-defibrillator (ICD) therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial to determine whether patients who receive an ICD after VT have arrhythmias during follow-up that are different from patients who present with VF. ICD printouts were analyzed both by a committee blinded to the patients' original presenting arrhythmia and by the local investigator. During 31 +/- 14 months of follow-up, 2,673 therapies were reported. Patients who were enrolled in the AVID trial after an episode of VT were more likely to have an episode of VT (73.5% vs 30.1%, p <0.001), and were less likely to have an episode of VF (18.3% vs 28.0%, p = 0.013) than patients enrolled after an episode of VF. Adjustment for differences in ejection fraction, previous infarction, and beta-blocker and antiarrhythmic therapy did not appreciably change the results. Ventricular arrhythmia recurrence during follow-up is different in patients who originally present with VT than in those who originally present with VF. These findings suggest there are important differences in the electrophysiologic characteristics of these 2 patient populations.

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.

Factors determining ICD implantation in drug therapy patients after termination of antiarrythmics versus implantable defibrillators trial.

Because of a significant survival benefit in the defibrillator arm of the Antiarrhythmics versus Implantable Defibrillator (AVID) Trial, patients in the antiarrhythmic drug (AAD) arm were advised to undergo ICD implantation. Despite this recommendation, ICD implantation in AAD patients was variable, with a large number of patients not undergoing ICD implantation. Patients were grouped by those who had been on AAD < 1 year (n = 111) and those on AAD > 1 year (n = 223). Multiple clinical and socioeconomic factors were evaluated to identify those who might be associated with a decision to implant an ICD. The primary reason for patients not undergoing ICD implantation was collected, as well as reasons for a delayed implantation, occurring later than 3 months from study termination. Of 111 patients on AAD for less than 1 year, 53 received an ICD within 3 months compared to 40/223 patients on AAD for more than 1 year (P < 0.001). Patient refusal was the most common reason to not implant an ICD in patients on drug < 1 year; physician recommendation against implantation was the most common in patients on drug > 1 year. Multivariate analysis showed ICD recipients on AAD < 1 year were more likely to be working and have a history of myocardial infarction (MI), while those on AAD > 1 year were more likely to be working, have a history of MI and ventricular fibrillation, and less likely to have experienced syncope, as compared to those who did not get an ICD. Having private insurance may have played a role in younger patients receiving an ICD.

Analysis of implantable cardioverter defibrillator therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial.

INTRODUCTION: The implantable cardioverter defibrillator (ICD) is commonly used to treat patients with documented sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Arrhythmia recurrence rates in these patients are high, but which patients will receive a therapy and the forms of arrhythmia recurrence (VT or VF) are poorly understood. METHODS AND RESULTS: The therapy delivered by the ICD was examined in 449 patients randomized to ICD therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial. Events triggering ICD shocks or antitachycardia pacing (ATP) were reviewed for arrhythmia diagnosis, clinical symptoms, activity at the onset of the arrhythmia, and appropriateness and results of therapy. Both shock and ATP therapies were frequent by 2 years, with 68% of patients receiving some therapy or having an arrhythmic death. An appropriate shock was delivered in 53% of patients, and ATP was delivered in 68% of patients who had ATP activated. The first arrhythmia treated in follow-up was diagnosed as VT (63%), VF (13%), supraventricular tachycardia (18%), unknown arrhythmia (3%), or due to ICD malfunction or inappropriate sensing (3%). Acceleration of an arrhythmia by the ICD occurred in 8% of patients who received any therapy. No physical activity consistently preceded arrhythmias, nor did any single clinical factor predict the symptoms of the arrhythmia. CONCLUSION: Delivery of ICD therapy in AVID patients was common, primarily due to VT. Inappropriate ICD therapy occurred frequently. Use of ICD therapy as a surrogate endpoint for death in clinical trials should be avoided.