The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial
Abstract & Commentary
Synopsis: DDDR pacing using a right ventricular lead in patients without an indication for antibradycardia pacing is detrimental. Therefore, for patients with standard indications for ICD therapy and no standard indication for cardiac pacing, dual-chamber pacing offers no clinical advantage over ventricular back-up pacing and may be detrimental.
Source: The DAVID Trial Investigators. JAMA. 2002; 288:3115-3123.
The david trial was designed to see if aggressive dual chamber pacing would benefit patients with implantable cardioverter defibrillators (ICDs) even in the absence of an accepted bradycardia indication for pacing.
The trial recruited patients who had a standard indication for an implantable cardioverter defibrillator. These criteria for ICD insertion included both primary and secondary therapy for ventricular arrhythmias. Patients with known symptomatic bradycardia or secondary third-degree AV block or current or unstable atrial arrhythmias were excluded. All patients underwent implantation of an ICD with dual-chamber pacing capability. After implant, patients were randomly assigned to have the pacing function of the device initially programmed to either the VVI mode with a lower rate of 40 bpm (VVI-40) or to the DDDR mode with a lower rate of 70 bpm (DDDR-70). Supraventricular tachycardia detection enhancements could be used only in the DDDR mode. Tachyarrhythmia detection was set to 150 bpm or slower and diagnostic features were set to collect atrial and ventricular bipolar electrograms and markers during ventricular tachyarrhythmia episodes for all patients. Optimal pharmacologic therapy for left ventricular dysfunction and heart failure was recommended for all patients. Antiarrhythmic drug therapy could be used when thought necessary by the investigator. Amiodarone was the preferred agent for both supraventricular and ventricular arrhythmias. Crossover from one pacing mode to another was discouraged and required permission from the clinical trial center.
The combined primary end point was freedom from death or hospitalization from heart failure. Events were reviewed by an events committee, which made the final decision on each reported end point.
A total of 506 patients were enrolled and randomized in the trial. The mean age was 65 years and 83% were male. Approximately equal numbers of patients received their ICD for primary and secondary prevention reasons. There were no major differences in the use of various cardiac drugs between the 2 groups. The mean left ventricular ejection fraction was 27%, but only 12% of the patients were New York Heart Association functional Class III or IV. Sixty-nine percent of the patients had a QRS duration of less than 130 m/sec. Subsequent to randomization but not during the baseline hospitalization, new or worsened heart failure occurred in 4.2% of the DDDR-70 group vs 0.8% of patients in the VVI-40 group. New or worsened heart failure during the initial hospitalization was not counted as a primary end point. Recurrent ventricular arrhythmias requiring therapy during the hospitalization for ICD implantation were slightly more frequent in the DDDR-70 group (7.5%) than in the VVI-40 group (5.9%).
The trial was stopped by the Data Safety Monitoring Board after a median follow-up of 8.4 months. There were fewer deaths and hospitalizations for new or worsened heart failure in the VVI-40 group. The hazard ratio was 1.61 with a 95% confidence interval of 1.06-2.44 (P < 0.03). One-year survival free of the composite end point was 83.9% for the VVI-40 patients compared with 73.3% for the DDDR-70 patients. Both rates of congestive heart failure hospitalization (13.3% vs 22.6%) and death rates (6.5% vs 10.1%) were higher in the DDDR-70 group. When the percentage of right ventricular paced beats was correlated with survival, it was found that patients with a higher percentage of right ventricular pacing had worse 12-month event-free rates.
The investigators conclude that DDDR pacing using a right ventricular lead in patients without an indication for antibradycardia pacing is detrimental. Therefore, for patients with standard indications for ICD therapy and no standard indication for cardiac pacing, dual-chamber pacing offers no clinical advantage over ventricular back-up pacing and may be detrimental.
The DAVID investigators optimistically hoped that they would be able to show an improved survival with the use of dual-chamber pacing in patients with implantable cardioverter defibrillators. I term this an optimistic hypothesis since it has been difficult to show that dual-chamber pacing benefits even those with accepted bradycardia indications for permanent pacing. For example, in the Canadian Trial of Physiologic Pacing,1 there was no significant improvement in the rate of stroke or death due to cardiovascular causes with physiologic pacing as opposed to ventricular pacing. There was, however, a significant improvement in the development of atrial fibrillation with the addition of atrial pacing, primarily in patients with sinus node dysfunction.
The patients in the DAVID trial had an indication for an ICD but did not have bradycardia. Therefore, we would have expected improved survival only if the higher heart rate associated with DDDR pacing at 70 bpm improved their hemodynamics or their risk for arrhythmia. The study also allowed activation of supraventricular tachycardia detection enhancements based on the information provided by the atrial electrogram, but one would not have expected successful use of these enhancements to result in a mortality benefit.
Since the trial was terminated early for safety reasons, the investigators thought it important to publish data before many secondary end points could be analyzed. It will be important to see if there is a decrease of inappropriate shocks for supraventricular arrhythmias associated with the addition of the atrial lead. If this is so, it may be appropriate to implant a dual-chamber defibrillator even if the atrial lead is used only for diagnostic purposes initially.
The mechanism by which the increase in early heart failure was seen is probably related to overuse of right ventricular pacing in patients who normally had narrow QRS complexes. It has been shown in patients with myocardial dysfunction that there can be adverse hemodynamic side effects from right ventricular pacing. The DAVID trial data indicate that in many patients with significant ventricular dysfunction biventricular pacing may be preferred to just right ventricular pacing in patients who will depend on the pacemaker functions of their ICD to prevent bradycardia.
Reference
1. Connolly SJ, et al. N Engl J Med. 2000;342:1385-1391.
Synopsis: DDDR pacing using a right ventricular lead in patients without an indication for antibradycardia pacing is detrimental.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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