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Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial - DAVID
Description:
Implantable cardioverter defibrillator (ICD) therapy with dual-chamber pacing vs with only ventricular backup pacing in patients LV dysfunction
Hypothesis:
Treatment of left ventricular (LV) dysfunction with optimized drug therapy and dual-chamber pacing will improve the combined endpoint of mortality and heart failure hospitalization compared with similarly optimized drug therapy with ventricular backup pacing in patients with LV dysfunction and standard indications for ICD therapy but not for pacing.
Study Design
Study Design:
Patients Screened: 760
Patients Enrolled: 506
NYHA Class: Class III or IV: 12%
Mean Follow Up: median 8.4 months (up to 23.6 months)
Mean Patient Age: mean age 65 years
Female: 16
Mean Ejection Fraction: Mean LVEF 28% in VVI arm vs 26% in DDDR arm (p=0.17)
Patient Populations:
One of the following: documented VF and LVEF <=40%; syncopal sustained VT and LVEF <=40%; nonsyncopal VT and LVEF <=40% and one of the following: sustained VT, systolic blood pressure <80 mm Hg, or significant cardiac symptoms; NSVT with significant symptoms and EPS-inducible sustained VT or VF; NSVT (minimal or no symptoms) and EPS-inducible sustained VT or VF; out-of-hospital unexplained syncope, heart disease, and EPS-inducible sustained VT or VF, and LVEF <=40%; hemodynamically stable sustained VT and LVEF <=40%; EPS-inducible VT or VF within 6 weeks prior to randomization and LVEF <=40%.
Exclusions:
Permanent pacemaker; preexisting endocardial pacing leads; CABG, PCI, cardiac, or other arrhythmia surgery planned but not yet performed (temporary exclusion); symptomatic bradycardia or second- or third-degree AV block; disqualifying atrial fibrillation (AF of unknown duration, AF >6 months duration, AF at randomization, need for electrical or chemical cardioversion in the last month); frequent, uncontrolled atrial tachyarrhythmia; awaiting cardiac transplantation; condition likely to limit cooperation; geographically inaccessible; enrolled in a conflicting study; prisoner or ward of the state; unable to give informed consent; life expectancy <1 year.
Primary Endpoints:
Time to death or heart failure hospitalization.
Secondary Endpoints:
Mortality CHF hospitalization
Drug/Procedures Used:
An ICD with dual-chamber, rate-responsive pacing capability was implanted in all patients. ICDs were programmed to 1) ventricular backup pacing at 40/min (VVI-40; n=256) or 2) dual-chamber rate-responsive pacing at 70/min (DDDR-70; n=250). All patients were also treated with medical therapy for LV dysfunction including ACE inhibitors, beta-blockers, digoxin, and diuretics.
Principal Findings:
DAVID was discontinued early by the DSMB due to a trend toward worse outcome with DDDR-70 pacing vs VVI-40 (p<0.03). Nearly all patients were treated with pharmacologic therapy for LV dysfunction during the index hospitalization (96%). Survival free of the composite end point (death or HF hospitalization) occurred in 83.9% of patients in the VVI-40 arm vs 73.3% of patients in the DDDR-70 arm at 1 year (relative hazard 1.61, p=0.03). Mortality occurred in 6.5% of the VVI-40 arm vs 10.1% for DDDR-70 (relative hazard 1.61, p=0.15). CHF hospitalization also trended higher in the DDDR-70 arm (13.3% for VVI-40 vs 22.6% for DDDR-70, relative hazard 1.54, p=0.07).
Interpretation:
Contrary to the prespecified hypothesis, treatment with dual-chamber pacing was associated with an increase in mortality or CHF hospitalizations by 1 year compared with ventricular backup pacing in patients with LV dysfunction and standard indications for ICD therapy but not for pacing. The effectiveness of single-chamber backup pacing ICDs has been previously established in many trials including the AVID and MADIT I trials. However, the DAVID trial addresses the effectiveness of dual chamber ICDs, which are frequently implanted. As the authors noted, two very different patient populations were enrolled in the pacemaker mode selection and the ICD trials. In the pacemaker trials, patients required antibradycardia pacing but only a small proportion of patients in the defibrillator trials needed antibradycardia stimulation. Additionally, in the pacemaker trials, LV function was normal or near normal in most patients but in the defibrillator trials LV function was severely impaired in a large majority of patients. Such differences may explain the dissimilar clinical outcomes in the trials. The authors speculate that the negative impact of DDDR pacing on mortality and heart failure may be due to 1) increased heart rate from the atrial pacing, 2) reduction in the PR interval due to ventricular pacing at the end of the AV interval or 3) the ventricular electrical activation proceeding from the right ventricular apex instead of through the existing conduction system. More than half of the patients in the MADIT II trial of patients without a prior episode of arrhythmia but with LV dysfunction had a dual-chamber defibrillator implanted. While MADIT II demonstrated a mortality benefit with ICD therapy compared with conventional medical therapy, the rate of hospitalization for heart failure trended to occur more frequently in the ICD arm (19.9% vs 14.9%, p=0.09). The possible explanation for this trend is more clearly understood with the current results of the DAVID trial.
References:
JAMA 2002;288(24):3115-3123.
Keywords: Digoxin, Ventricular Fibrillation, Diuretics, Heart Failure, Syncope, Pacemaker, Artificial, Blood Pressure, Heart Rate, Defibrillators, Implantable, Tachycardia
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