DATAS shows benefit of dual-chamber ICDs?
DATAS shows benefit of dual-chamber ICDs?
Nice, France - A dual-chamber implantable cardioverter-defibrillator (ICD) showed greater efficacy in reducing clinically significant adverse events than a single-chamber ICD among patients with a standard ICD indication in the Dual Chamber and Atrial Tachyarrhythmias Adverse Events Study (DATAS).
The trial was presented at Cardiostim 2006, the 15th World Congress in Cardiac Electrophysiology and Cardiac Techniques, held in Nice, France, last month.
The study is important because it restores confidence in the idea of dual-chamber ICDs, which has taken a knock after the results of the DAVID trial showed a worse outcome with dual-chamber vs single-chamber devices. So why the different results? Several experts consulted by heart wire said that the primary explanation for the difference between the two trials appears to be the different amounts of pacing provided by the ICDs; the dual-chamber device used in DAVID had a much higher degree of pacing activity than the one used in DATAS. And the consensus from the two trials appears to be that dual-chamber ICDs might be superior, as long as the pacing function is kept to a minimum.
One cardiologist pointed out that the DATAS results are not definitive and need to be confirmed in trials with longer follow-ups. Commenting on the study for heart wire , Dr William Maisel (Beth Israel Deaconess Medical Center, Boston, MA) explained that because of the crossover design in the DATAS study, patients in the dual-chamber group were only followed for an average of eight months when the device was actually active in both chambers. "In the DAVID study, the deleterious effect of the dual-chamber device on heart-failure hospitalizations didn't show up until after eight months, so I would be cautious when interpreting the results of the DATAS trial. Yes, it is a provocative study, but I don't think it is conclusive, and the results need to be confirmed in good randomized trials with longer follow-ups," he said.
DATAS rationale
Presenting the DATAS trial at the Cardiostim meeting, Dr Jesus Almendral (Hospital General Universitario Gregorio Maranon, Madrid, Spain) explained the rationale for the study. He noted that single-chamber ICDs sense bradycardia, detect arrhythmias, and provide pacing in the right ventricle only, which might result in incomplete sensing and therapy in some patients. They can also deliver inappropriate shocks, particularly in patients who have atrial fibrillation. Dual-chamber ICDs overcome these issues—they monitor both the right atrium and the right ventricle, can defibrillate the ventricle, and pace both the atrium and the ventricle in atrioventricular (AV) synchrony. In addition, dual-chamber ICDs provide superior supraventricular tachycardia discrimination to further reduce inappropriate shocks. However, dual-chamber devices are more complicated to implant and might have an adverse right-ventricular-pacing effect, as seen in the DAVID trial, which questioned the long-term safety and efficacy of such devices. Whether or not the costs and complexity of dual-chamber devices offer a real clinical advantage is therefore a controversial issue, he said.
The DATAS investigators hypothesized that if device-related complications are low and the adverse pacing effects are minimized by strict programming, dual-chamber ICDs might have fewer clinically significant adverse effects than single-chamber ICDs.
To test this hypothesis, they conducted the DATAS trial, supported by Medtronic, which included 334 patients at risk of sudden cardiac death. Participating centers included consecutive patients with a standard ICD indication who were randomly assigned to dual- or single-chamber ICDs. The dual-chamber group was crossed over halfway through the study—the ICD was reprogrammed as a single-chamber device to monitor electrode-related adverse effects and arrhythmias (single-chamber simulated group). Patients were followed for 17 months in the single-chamber ICD group and for eight months for each crossover phase in the dual-chamber group. The primary end point was the clinically significant adverse events score, calculated by combining scores for death, invasive interventions, hospitalizations, inappropriate shocks, and sustained long-duration atrial tachyarrhythmias, adjusted according to clinical severity.
Results showed that the rate of clinically significant adverse events was 33% lower with the dual-chamber ICDs than with the single-chamber devices (p=0.003).
Clinically significant adverse events (CSAE) score
Actual events
In an interview with heartwire , DATAS investigator Dr Aurelio Quesada (Hospital General Universitario de Valencia, Spain) said he believed the reason this study showed a benefit of dual-chamber devices when the DAVID study did not was because of the different degrees of right ventricular pacing produced by the dual-chamber ICDs used in the two studies. "We controlled the AV interval with the dual-chamber device in our study, but this was not done in the DAVID trial, and consequently the DAVID trial had a much higher rate of right ventricular pacing—around 66%, compared with 36% in our study. We recommend that physicians program their devices as we did, for long AV intervals—about 200 milliseconds," he stated.
Other differences between the two studies that Quesada pointed out were a lower mean ejection fraction in the patients in the DAVID study—with an average of about 25% vs 36% in DATAS—and the fact that the device used in the DATAS trial also treated atrial tachyarrhythmias, whereas the one used in DAVID did not.
Minimal pacing appears to be the key
Most experts asked to comment on the DATAS results for heart wire agreed that it was the fact that the dual-chamber device used in the DATAS study was programmed to have a low frequency of pacing that was the key to its success.
Dr Andrew Clark (University of Hull, UK) said: "I believe that the reason DAVID showed a worse result with a dual-chamber ICD than a single-chamber ICD was because of the built-in pacing function of the dual-chamber device used; it had nothing to do with the actual defibrillation. DAVID really put the cat among the pigeons as, until this time, everyone believed dual-chamber ICDs, which also paced and therefore maintained a normal heart rhythm, were the best option. But in the DAVID study, patients in the dual-chamber group did worse than those in the single-chamber group."
"Many people have interpreted DAVID as having shown that pacing the atrium and ventricle together is not a good idea, but this does not mean that dual-chamber ICDs are not the way forward. In the DATAS trial, the dual-chamber ICD used seems to have been programmed not to pace unless the heart starts to beat very slowly. This reduces unnecessary pacing, but [the device] can still sense activity in both the left atrium and ventricle and deliver shocks when appropriate," Clark said.
He added: "I think that DAVID showed that pacing from the right ventricle is bad for you. When you pace, you stick an electrode in the apex of the right ventricle, which causes the heart to be depolarized from the wrong place, which results in a worse outcome. But some degree of pacing is obviously needed in an ICD to keep the heart going if it slows down too much—it would be a brave person that turned off the pacing function completely; the key seems to be to program the ICD to only pace at very low heart rates."
Dr Kenneth Ellenbogen (Medical College of Virginia, Richmond) agrees. "The DATAS study is a very important study in that it shows that there are advantages of having a second lead in an ICD," he commented to heart wire . "The message from this study should be that as long as the right ventricle is not being paced inappropriately, dual-chamber pacing is a good thing, and we should start to feel more comfortable about using dual-chamber devices again."
Ellenbogen explained that it is not necessarily the brand of dual-chamber device that is important but rather how it is programmed. "In DAVID, the dual-chamber device was programmed so that ventricular pacing was forced, but in DATAS, ventricular pacing was not forced. This seems to explain the different results of these two studies," he said.
Ellenbogen is involved in a similar but larger study, which he hopes will confirm this hypothesis. This study, also sponsored by Medtronic, will involve around 1000 patients, have a longer follow-up than DATAS, and will use a dual-chamber ICD programmed to have even less pacing activity. "We are going for a real minimum pacing rate—less than 5%—which we believe should show even better results," he told heart wire . "DATAS is a good starting point—it has suggested the way forward, but our study will be more definitive," he added.
A voice of caution
But Maisel was more cautious in his interpretation of the DATAS results. In addition to the short follow-up issue, he pointed out that the reduction in the composite end point was driven by reductions in long-duration atrial tachyarrhythmias and inappropriate shocks, neither of which were a surprise. "The dual-chamber device used in DATAS intervened on atrial tachycardia, so of course you're going to get less long-duration atrial tachycardia occurring. I'm not sure that this should have been part of the composite end point. And it is already established that dual-chamber devices reduce inappropriate shocks, so that was also an expected result. But DATAS did not show a reduction in hospitalization—actually there were numerically more hospitalizations in the dual-chamber group," he noted.
"I think that this trial provides justification for use of a dual-chamber device in certain patients to reduce atrial tachycardia and inappropriate shocks, but it does not suggest that all patients should receive them. It also suggests that device programming may be able to overcome some of the harm that dual-chamber devices caused in DAVID, but I don't think the results are conclusive in this regard because of the inadequate follow-up," Maisel concluded.
Nice, France - A dual-chamber implantable cardioverter-defibrillator (ICD) showed greater efficacy in reducing clinically significant adverse events than a single-chamber ICD among patients with a standard ICD indication in the Dual Chamber and Atrial Tachyarrhythmias Adverse Events Study (DATAS).
The trial was presented at Cardiostim 2006, the 15th World Congress in Cardiac Electrophysiology and Cardiac Techniques, held in Nice, France, last month.
The study is important because it restores confidence in the idea of dual-chamber ICDs, which has taken a knock after the results of the DAVID trial showed a worse outcome with dual-chamber vs single-chamber devices. So why the different results? Several experts consulted by heart wire said that the primary explanation for the difference between the two trials appears to be the different amounts of pacing provided by the ICDs; the dual-chamber device used in DAVID had a much higher degree of pacing activity than the one used in DATAS. And the consensus from the two trials appears to be that dual-chamber ICDs might be superior, as long as the pacing function is kept to a minimum.
One cardiologist pointed out that the DATAS results are not definitive and need to be confirmed in trials with longer follow-ups. Commenting on the study for heart wire , Dr William Maisel (Beth Israel Deaconess Medical Center, Boston, MA) explained that because of the crossover design in the DATAS study, patients in the dual-chamber group were only followed for an average of eight months when the device was actually active in both chambers. "In the DAVID study, the deleterious effect of the dual-chamber device on heart-failure hospitalizations didn't show up until after eight months, so I would be cautious when interpreting the results of the DATAS trial. Yes, it is a provocative study, but I don't think it is conclusive, and the results need to be confirmed in good randomized trials with longer follow-ups," he said.
DATAS rationale
Presenting the DATAS trial at the Cardiostim meeting, Dr Jesus Almendral (Hospital General Universitario Gregorio Maranon, Madrid, Spain) explained the rationale for the study. He noted that single-chamber ICDs sense bradycardia, detect arrhythmias, and provide pacing in the right ventricle only, which might result in incomplete sensing and therapy in some patients. They can also deliver inappropriate shocks, particularly in patients who have atrial fibrillation. Dual-chamber ICDs overcome these issues—they monitor both the right atrium and the right ventricle, can defibrillate the ventricle, and pace both the atrium and the ventricle in atrioventricular (AV) synchrony. In addition, dual-chamber ICDs provide superior supraventricular tachycardia discrimination to further reduce inappropriate shocks. However, dual-chamber devices are more complicated to implant and might have an adverse right-ventricular-pacing effect, as seen in the DAVID trial, which questioned the long-term safety and efficacy of such devices. Whether or not the costs and complexity of dual-chamber devices offer a real clinical advantage is therefore a controversial issue, he said.
The DATAS investigators hypothesized that if device-related complications are low and the adverse pacing effects are minimized by strict programming, dual-chamber ICDs might have fewer clinically significant adverse effects than single-chamber ICDs.
To test this hypothesis, they conducted the DATAS trial, supported by Medtronic, which included 334 patients at risk of sudden cardiac death. Participating centers included consecutive patients with a standard ICD indication who were randomly assigned to dual- or single-chamber ICDs. The dual-chamber group was crossed over halfway through the study—the ICD was reprogrammed as a single-chamber device to monitor electrode-related adverse effects and arrhythmias (single-chamber simulated group). Patients were followed for 17 months in the single-chamber ICD group and for eight months for each crossover phase in the dual-chamber group. The primary end point was the clinically significant adverse events score, calculated by combining scores for death, invasive interventions, hospitalizations, inappropriate shocks, and sustained long-duration atrial tachyarrhythmias, adjusted according to clinical severity.
Results showed that the rate of clinically significant adverse events was 33% lower with the dual-chamber ICDs than with the single-chamber devices (p=0.003).
Clinically significant adverse events (CSAE) score
| Dual chamber, n=112 | Single chamber, n=111 | Single chamber (simulated), n=111 | |
| Absolute number of events | 65 | 82 | 84 |
| CSAE score | 138 | 193 | 231 |
Actual events
| Dual chamber, n=112 | Single chamber, n=111 | Single chamber (simulat ed), n=111 | |
| Death (%) | 4 | 9 | 10 |
| Invasive interventions (%) | 9 | 10 | 11 |
| Hospitalizations (%) | 42 | 38 | 46 |
| Inappropriate shocks (%) | 3 | 12 | 6 |
| Long-duration atrial tachyarrhythmia (%) | 1 | 5 | 3 |
In an interview with heartwire , DATAS investigator Dr Aurelio Quesada (Hospital General Universitario de Valencia, Spain) said he believed the reason this study showed a benefit of dual-chamber devices when the DAVID study did not was because of the different degrees of right ventricular pacing produced by the dual-chamber ICDs used in the two studies. "We controlled the AV interval with the dual-chamber device in our study, but this was not done in the DAVID trial, and consequently the DAVID trial had a much higher rate of right ventricular pacing—around 66%, compared with 36% in our study. We recommend that physicians program their devices as we did, for long AV intervals—about 200 milliseconds," he stated.
Other differences between the two studies that Quesada pointed out were a lower mean ejection fraction in the patients in the DAVID study—with an average of about 25% vs 36% in DATAS—and the fact that the device used in the DATAS trial also treated atrial tachyarrhythmias, whereas the one used in DAVID did not.
Minimal pacing appears to be the key
Most experts asked to comment on the DATAS results for heart wire agreed that it was the fact that the dual-chamber device used in the DATAS study was programmed to have a low frequency of pacing that was the key to its success.
Dr Andrew Clark (University of Hull, UK) said: "I believe that the reason DAVID showed a worse result with a dual-chamber ICD than a single-chamber ICD was because of the built-in pacing function of the dual-chamber device used; it had nothing to do with the actual defibrillation. DAVID really put the cat among the pigeons as, until this time, everyone believed dual-chamber ICDs, which also paced and therefore maintained a normal heart rhythm, were the best option. But in the DAVID study, patients in the dual-chamber group did worse than those in the single-chamber group."
"Many people have interpreted DAVID as having shown that pacing the atrium and ventricle together is not a good idea, but this does not mean that dual-chamber ICDs are not the way forward. In the DATAS trial, the dual-chamber ICD used seems to have been programmed not to pace unless the heart starts to beat very slowly. This reduces unnecessary pacing, but [the device] can still sense activity in both the left atrium and ventricle and deliver shocks when appropriate," Clark said.
He added: "I think that DAVID showed that pacing from the right ventricle is bad for you. When you pace, you stick an electrode in the apex of the right ventricle, which causes the heart to be depolarized from the wrong place, which results in a worse outcome. But some degree of pacing is obviously needed in an ICD to keep the heart going if it slows down too much—it would be a brave person that turned off the pacing function completely; the key seems to be to program the ICD to only pace at very low heart rates."
Dr Kenneth Ellenbogen (Medical College of Virginia, Richmond) agrees. "The DATAS study is a very important study in that it shows that there are advantages of having a second lead in an ICD," he commented to heart wire . "The message from this study should be that as long as the right ventricle is not being paced inappropriately, dual-chamber pacing is a good thing, and we should start to feel more comfortable about using dual-chamber devices again."
Ellenbogen explained that it is not necessarily the brand of dual-chamber device that is important but rather how it is programmed. "In DAVID, the dual-chamber device was programmed so that ventricular pacing was forced, but in DATAS, ventricular pacing was not forced. This seems to explain the different results of these two studies," he said.
Ellenbogen is involved in a similar but larger study, which he hopes will confirm this hypothesis. This study, also sponsored by Medtronic, will involve around 1000 patients, have a longer follow-up than DATAS, and will use a dual-chamber ICD programmed to have even less pacing activity. "We are going for a real minimum pacing rate—less than 5%—which we believe should show even better results," he told heart wire . "DATAS is a good starting point—it has suggested the way forward, but our study will be more definitive," he added.
A voice of caution
But Maisel was more cautious in his interpretation of the DATAS results. In addition to the short follow-up issue, he pointed out that the reduction in the composite end point was driven by reductions in long-duration atrial tachyarrhythmias and inappropriate shocks, neither of which were a surprise. "The dual-chamber device used in DATAS intervened on atrial tachycardia, so of course you're going to get less long-duration atrial tachycardia occurring. I'm not sure that this should have been part of the composite end point. And it is already established that dual-chamber devices reduce inappropriate shocks, so that was also an expected result. But DATAS did not show a reduction in hospitalization—actually there were numerically more hospitalizations in the dual-chamber group," he noted.
"I think that this trial provides justification for use of a dual-chamber device in certain patients to reduce atrial tachycardia and inappropriate shocks, but it does not suggest that all patients should receive them. It also suggests that device programming may be able to overcome some of the harm that dual-chamber devices caused in DAVID, but I don't think the results are conclusive in this regard because of the inadequate follow-up," Maisel concluded.
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