Background
Cardiac resynchronization therapy with defibrillator support, commonly called CRT-D, is used in selected patients with heart failure to improve the coordination of the heart’s pumping action and reduce the risk of dangerous arrhythmias. In the standard system, three leads are usually implanted: one in the right atrium, one in the right ventricle, and one in a vein on the left side of the heart to stimulate the left ventricle. The right atrial lead helps the device sense and, when needed, pace the atrium to maintain an appropriate heart rate and preserve atrioventricular timing.
However, the benefit of atrial pacing support is uncertain in patients who do not have sinus node dysfunction, meaning their own natural heart pacemaker still works adequately. In such patients, an atrial lead may add complexity without clearly improving outcomes. It may also introduce additional lead-related complications over time, such as lead failure, dislodgment, or sensing problems. This trial was designed to test whether a two-lead CRT-D system that can sense atrial activity through a floating dipole on the right ventricular lead, but cannot pace the atrium, is not inferior to the conventional three-lead system.
Study Design
This was a randomized, parallel-group, noninferiority trial conducted at 23 sites in Italy. From October 17, 2018, through March 5, 2024, 636 patients with a standard indication for CRT-D, optimized medical therapy, and a resting sinus rate of at least 45 beats per minute were enrolled. The average age was 68 years, and 28.6% were women. Patients were randomly assigned in a 1:1 ratio to receive either CRT-DX, the two-lead system with atrial sensing but no atrial pacing, or conventional CRT-D with a standard atrial lead.
The study used centralized block randomization stratified by site. Both patients and the investigators assessing the primary outcomes were blinded to the treatment assignment. In the CRT-DX group, the device was programmed to track atrial activity without atrial pacing, with a lower pacing mode of 35 beats per minute. In the conventional CRT-D group, atrial tracking and atrial pacing were enabled, with a lower pacing mode of 50 beats per minute.
The main outcome was a composite at 1 year that included all-cause death, cardiovascular hospitalization, and lead-related complications that could not be corrected by device reprogramming. Secondary outcomes included each component of the primary endpoint separately, echocardiographic reverse remodeling, and distance covered on the 6-minute walk test at 12 months.
Main Findings
The primary composite endpoint occurred in 41 patients, or 13.1%, in the CRT-DX group and in 47 patients, or 15.6%, in the conventional CRT-D group. This corresponded to a hazard ratio of 0.82 with a 95% confidence interval of 0.54 to 1.25. These results met the prespecified criteria for noninferiority, with the relative margin set at 1.20, in both the per-protocol analysis and the intention-to-treat analysis.
In practical terms, this means that the two-lead system performed at least as well as the standard three-lead system for the main combined outcome, without showing evidence that it was worse within the predefined acceptable limit.
When the individual components of the primary endpoint were examined separately, there were no major differences between the two groups, except for lead complications related specifically to right atrial functionality. These complications were less frequent in the CRT-DX group: 4 patients, or 1.3%, compared with 13 patients, or 4.2%, in the conventional CRT-D group. This difference reached statistical significance.
Remodeling and Functional Capacity
A key goal of CRT is reverse remodeling, meaning improvement in the heart’s size and shape as well as better mechanical efficiency after treatment. Among patients who underwent echocardiographic follow-up, reverse remodeling responders were seen in 203 of 262 patients in the CRT-DX group, or 77.5%, and in 190 of 249 patients in the conventional CRT-D group, or 76.3%. This difference was not significant, indicating that the absence of a dedicated atrial pacing lead did not reduce the chance of structural improvement.
Functional exercise capacity also appeared similar. At 12 months, the 6-minute walk distance was 404 meters in the CRT-DX group and 398 meters in the conventional CRT-D group, with no significant difference. This suggests that day-to-day physical performance and symptom-related activity were broadly comparable between strategies.
Longer-Term Follow-Up
The median follow-up was 2.4 years. During this period, only one patient in the CRT-DX group required implantation of a standard atrial lead. This is an important real-world observation because it suggests that, for most patients without sinus node dysfunction, atrial pacing support is not needed even over a longer follow-up period.
Clinical Interpretation
The findings support a simpler device strategy in appropriately selected patients. If a patient with heart failure and standard CRT-D indication has preserved sinus node function and resting sinus rhythm is sufficiently stable, a two-lead CRT-DX system may provide the desired resynchronization benefit while reducing the burden of an extra atrial lead.
This is clinically meaningful for several reasons. First, fewer implanted leads can mean less procedural complexity. Second, it may lower the risk of atrial lead failure or malfunction, which can lead to repeat procedures, device reprogramming, or additional costs. Third, avoiding unnecessary hardware may improve long-term device reliability.
That said, the study does not imply that atrial pacing is never useful. Patients with sinus node dysfunction, intermittent bradycardia, chronotropic incompetence, or other atrial rhythm problems may still benefit from a conventional atrial lead. The results apply specifically to the studied population: patients receiving CRT-D who had no clear need for atrial pacing at baseline.
Why This Matters
In heart failure care, device selection should balance benefit, safety, and simplicity. CRT has a strong evidence base for improving symptoms and outcomes in selected patients with reduced left ventricular function and electrical dyssynchrony. But every added lead increases the chance of lead-related issues over time. This trial suggests that, when atrial pacing is not required, omitting the atrial lead may be a reasonable and evidence-based approach.
For clinicians, the study may support more individualized device planning. For patients, it may translate into fewer lead-related complications without sacrificing symptom improvement or heart function recovery. In busy implant programs, a two-lead system may also streamline procedures and follow-up.
Limitations
As with any trial, there are limitations to keep in mind. The study was conducted in Italy, so results may need confirmation in other healthcare systems and patient populations. The follow-up for the main endpoint was 1 year, although longer-term follow-up extended beyond that period for some outcomes. Also, the trial focused on a selected group with resting sinus rate of at least 45 beats per minute, so the findings should not be generalized to patients with more significant bradycardia or known sinus node dysfunction.
Another point is that the primary endpoint was composite, combining death, hospitalization, and lead complications. Composite endpoints are useful for capturing overall clinical impact, but the individual components may differ in importance to patients. Here, the overall result was strengthened by the finding of fewer atrial lead-related complications in the CRT-DX group, while other outcomes were similar.
Conclusion
In this randomized noninferiority trial, the two-lead CRT-DX system without atrial pacing was not inferior to conventional three-lead CRT-D in patients who did not have sinus node dysfunction. It achieved similar rates of survival, cardiovascular hospitalization, reverse remodeling, and functional improvement, while reducing atrial lead-related complications.
For appropriately selected patients, a simpler CRT-D approach may be a safe and effective alternative to standard atrial lead implantation.