How to cut the CRT nonresponder rate

SNOWMASS, COLO. – The 12-lead Holter monitor is an invaluable and underutilized tool for turning cardiac resynchronization therapy nonresponders into responders, according to Dr. N.A. Mark Estes III.

“The Achilles heel of CRT right now is the failure to respond that occurs in one-quarter to one-third of patients who receive the device. And I think it’s less and less due to a problem of poor patient selection or technical failure, but instead due to common mistakes made in patients who’ve been properly selected and in whom a CRT device has been placed appropriately. I think there’s a lot of room for improvement here,” said Dr. Estes, director of the cardiac arrhythmia center and professor of medicine at Tufts University in Boston.

One common mistake is to accept at face value the CRT device counter when it shows a high percentage of ventricular pacing that’s supposed to be indicative of adequate biventricular pacing in patients. That’s not reliable in patients with coexisting heart failure and atrial fibrillation. In fact, the device pacing counter can markedly overestimate the degree of effective biventricular pacing in patients with permanent atrial fibrillation undergoing CRT. That’s because it may incorrectly count fusion and pseudofusion beats as paced events, even though ventricular capture and atrioventricular resynchronization fail to occur during such beats. The 12-lead Holter monitor will tell the real story regarding ventricular rate control and the percentage of fully paced beats, Dr. Estes said at the Annual Cardiovascular Conference at Snowmass.

“In patients with atrial fibrillation, you can’t just do an EKG, and you can’t just do an interrogation of the device and see that they have 90% or 95% biventricular pacing, which is the sweet spot you need to be North of to make sure they’re having benefit. You really need to do the 24-hour Holter monitor,” the cardiologist emphasized.

“It happens all the time,” he continued. “It happens in my own institution, where we have people come in with heart failure who are being evaluated for an LVAD [left ventricular assist device] because when their CRT device is interrogated, it shows 95% pacing. Everyone’s getting ready to put in the LVAD, and we put them on a Holter monitor and guess what? They’re 60% paced. And sometimes you can have dramatic – really dramatic – improvements by just slowing the ventricular response.”

Increasingly, however, he and his fellow electrophysiologists are alternatively turning to atrioventricular junction ablation in suitable candidates for the catheter-based procedure in order to improve their clinical response to CRT.

Dr. Estes cited a study by Columbia University cardiologists as being highly influential in shaping the new understanding of how to use 12-lead Holter monitoring to identify patients with atrial fibrillation who aren’t responding to CRT. They studied 19 patients with permanent atrial fibrillation who were on CRT, all of whom were on beta-blockers, amiodarone, and digoxin for rate control. Although device interrogation showed all 19 patients had in excess of 90% biventricular pacing 12 months after CRT implantation, only 9 patients were actually clinical responders to CRT as defined by at least a 1-grade improvement in New York Heart Association functional class.

Upon wearing an ambulatory 12-lead Holter monitor for 24 hours, only the nine patients with clinical improvement in response to CRT actually had effective pacing; 94% of their heart beats over the course of 24 hours were fully paced, with a mere 2% fusion beats and less than 4% pseudofusion beats. The other 10 patients had an average of only 60% fully paced beats, along with 16% fusion and 24% pseudofusion beats.

The CRT clinical responders also showed evidence of reverse remodeling, with significantly greater improvements in left ventricular ejection fraction, end-systolic dimension, end-diastolic diameter, and end-systolic and end-diastolic volume, compared with nonresponders.

The lesson, according to the investigators, is that the percentage of biventricular pacing, as obtained from CRT device interrogation, is an unreliable indicator of effective pacing in patients with permanent atrial fibrillation. The goal of CRT programming in this population is to try to achieve 100% biventricular capture on the 12-lead Holter monitor (J. Am. Coll. Cardiol. 2009;53:1050-5).

A series of landmark randomized trials has established that in suitable candidates for CRT with NYHA class I through ambulatory class IV heart failure with reduced ejection fraction, the device therapy provides on average about a 17% reduction in all-cause mortality and a 29% decrease in hospitalizations for heart failure above and beyond the benefits obtained through guideline-directed medical therapy. However, the improvements seen in patients with NYHA class I symptoms are less impressive than in those with NYHA class II-IV disease. And it’s possible that the randomized controlled trials overestimate the true benefit from CRT.

“This is a group of extremely experienced investigators who know the literature well. They’re typically quite savvy with patient selection, and they’re vested in getting the right patients into these trials. Unfortunately, there’s not a registry of all eligible patients, so we can’t tell exactly how those patients were selected. It would have been helpful,” Dr. Estes said.

It’s clear from the randomized trials that the ideal patient for CRT is a woman under age 65 with nonischemic cardiomyopathy with a left bundle branch block, normal sinus rhythm, and a QRS duration of 150 milliseconds or more. That’s who’s most likely to obtain clinical benefit from the therapy. The flip side of that is that an older male patient with ischemia, atrial fibrillation, a QRS of 120-150 milliseconds, and non–left bundle branch block is less likely to respond.

“We’ve figured this out. I think we’ve gotten pretty good at giving patients an honest estimate of their probability of responding independent of our ability to get a lead into a good spot in the coronary sinus,” Dr. Estes said. “More than 95% of patients can be adequately resynchronized currently with the tools we have, so it’s not the barrier that it once represented. We have many different techniques available.”

Despite intensive efforts by investigators using sophisticated nuclear studies, echocardiography, and MRI, however, nothing to date has been able to predict who’s going to respond to CRT as well as a simple electrical parameter: the QRS duration.

“It remains really the gold standard. It’s an electrical marker for what is a mechanical event,” Dr. Estes said.

He reported serving as a consultant to Medtronic, St. Jude Medical, and Boston Scientific and receiving research support from Boston Scientific and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The 12-lead Holter monitor is an invaluable and underutilized tool for turning cardiac resynchronization therapy nonresponders into responders, according to Dr. N.A. Mark Estes III.

“The Achilles heel of CRT right now is the failure to respond that occurs in one-quarter to one-third of patients who receive the device. And I think it’s less and less due to a problem of poor patient selection or technical failure, but instead due to common mistakes made in patients who’ve been properly selected and in whom a CRT device has been placed appropriately. I think there’s a lot of room for improvement here,” said Dr. Estes, director of the cardiac arrhythmia center and professor of medicine at Tufts University in Boston.

One common mistake is to accept at face value the CRT device counter when it shows a high percentage of ventricular pacing that’s supposed to be indicative of adequate biventricular pacing in patients. That’s not reliable in patients with coexisting heart failure and atrial fibrillation. In fact, the device pacing counter can markedly overestimate the degree of effective biventricular pacing in patients with permanent atrial fibrillation undergoing CRT. That’s because it may incorrectly count fusion and pseudofusion beats as paced events, even though ventricular capture and atrioventricular resynchronization fail to occur during such beats. The 12-lead Holter monitor will tell the real story regarding ventricular rate control and the percentage of fully paced beats, Dr. Estes said at the Annual Cardiovascular Conference at Snowmass.

“In patients with atrial fibrillation, you can’t just do an EKG, and you can’t just do an interrogation of the device and see that they have 90% or 95% biventricular pacing, which is the sweet spot you need to be North of to make sure they’re having benefit. You really need to do the 24-hour Holter monitor,” the cardiologist emphasized.

“It happens all the time,” he continued. “It happens in my own institution, where we have people come in with heart failure who are being evaluated for an LVAD [left ventricular assist device] because when their CRT device is interrogated, it shows 95% pacing. Everyone’s getting ready to put in the LVAD, and we put them on a Holter monitor and guess what? They’re 60% paced. And sometimes you can have dramatic – really dramatic – improvements by just slowing the ventricular response.”

Increasingly, however, he and his fellow electrophysiologists are alternatively turning to atrioventricular junction ablation in suitable candidates for the catheter-based procedure in order to improve their clinical response to CRT.

Dr. Estes cited a study by Columbia University cardiologists as being highly influential in shaping the new understanding of how to use 12-lead Holter monitoring to identify patients with atrial fibrillation who aren’t responding to CRT. They studied 19 patients with permanent atrial fibrillation who were on CRT, all of whom were on beta-blockers, amiodarone, and digoxin for rate control. Although device interrogation showed all 19 patients had in excess of 90% biventricular pacing 12 months after CRT implantation, only 9 patients were actually clinical responders to CRT as defined by at least a 1-grade improvement in New York Heart Association functional class.

Upon wearing an ambulatory 12-lead Holter monitor for 24 hours, only the nine patients with clinical improvement in response to CRT actually had effective pacing; 94% of their heart beats over the course of 24 hours were fully paced, with a mere 2% fusion beats and less than 4% pseudofusion beats. The other 10 patients had an average of only 60% fully paced beats, along with 16% fusion and 24% pseudofusion beats.

The CRT clinical responders also showed evidence of reverse remodeling, with significantly greater improvements in left ventricular ejection fraction, end-systolic dimension, end-diastolic diameter, and end-systolic and end-diastolic volume, compared with nonresponders.

The lesson, according to the investigators, is that the percentage of biventricular pacing, as obtained from CRT device interrogation, is an unreliable indicator of effective pacing in patients with permanent atrial fibrillation. The goal of CRT programming in this population is to try to achieve 100% biventricular capture on the 12-lead Holter monitor (J. Am. Coll. Cardiol. 2009;53:1050-5).

A series of landmark randomized trials has established that in suitable candidates for CRT with NYHA class I through ambulatory class IV heart failure with reduced ejection fraction, the device therapy provides on average about a 17% reduction in all-cause mortality and a 29% decrease in hospitalizations for heart failure above and beyond the benefits obtained through guideline-directed medical therapy. However, the improvements seen in patients with NYHA class I symptoms are less impressive than in those with NYHA class II-IV disease. And it’s possible that the randomized controlled trials overestimate the true benefit from CRT.

“This is a group of extremely experienced investigators who know the literature well. They’re typically quite savvy with patient selection, and they’re vested in getting the right patients into these trials. Unfortunately, there’s not a registry of all eligible patients, so we can’t tell exactly how those patients were selected. It would have been helpful,” Dr. Estes said.

It’s clear from the randomized trials that the ideal patient for CRT is a woman under age 65 with nonischemic cardiomyopathy with a left bundle branch block, normal sinus rhythm, and a QRS duration of 150 milliseconds or more. That’s who’s most likely to obtain clinical benefit from the therapy. The flip side of that is that an older male patient with ischemia, atrial fibrillation, a QRS of 120-150 milliseconds, and non–left bundle branch block is less likely to respond.

“We’ve figured this out. I think we’ve gotten pretty good at giving patients an honest estimate of their probability of responding independent of our ability to get a lead into a good spot in the coronary sinus,” Dr. Estes said. “More than 95% of patients can be adequately resynchronized currently with the tools we have, so it’s not the barrier that it once represented. We have many different techniques available.”

Despite intensive efforts by investigators using sophisticated nuclear studies, echocardiography, and MRI, however, nothing to date has been able to predict who’s going to respond to CRT as well as a simple electrical parameter: the QRS duration.

“It remains really the gold standard. It’s an electrical marker for what is a mechanical event,” Dr. Estes said.

He reported serving as a consultant to Medtronic, St. Jude Medical, and Boston Scientific and receiving research support from Boston Scientific and St. Jude Medical.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – The 12-lead Holter monitor is an invaluable and underutilized tool for turning cardiac resynchronization therapy nonresponders into responders, according to Dr. N.A. Mark Estes III.

“The Achilles heel of CRT right now is the failure to respond that occurs in one-quarter to one-third of patients who receive the device. And I think it’s less and less due to a problem of poor patient selection or technical failure, but instead due to common mistakes made in patients who’ve been properly selected and in whom a CRT device has been placed appropriately. I think there’s a lot of room for improvement here,” said Dr. Estes, director of the cardiac arrhythmia center and professor of medicine at Tufts University in Boston.

One common mistake is to accept at face value the CRT device counter when it shows a high percentage of ventricular pacing that’s supposed to be indicative of adequate biventricular pacing in patients. That’s not reliable in patients with coexisting heart failure and atrial fibrillation. In fact, the device pacing counter can markedly overestimate the degree of effective biventricular pacing in patients with permanent atrial fibrillation undergoing CRT. That’s because it may incorrectly count fusion and pseudofusion beats as paced events, even though ventricular capture and atrioventricular resynchronization fail to occur during such beats. The 12-lead Holter monitor will tell the real story regarding ventricular rate control and the percentage of fully paced beats, Dr. Estes said at the Annual Cardiovascular Conference at Snowmass.

“In patients with atrial fibrillation, you can’t just do an EKG, and you can’t just do an interrogation of the device and see that they have 90% or 95% biventricular pacing, which is the sweet spot you need to be North of to make sure they’re having benefit. You really need to do the 24-hour Holter monitor,” the cardiologist emphasized.

“It happens all the time,” he continued. “It happens in my own institution, where we have people come in with heart failure who are being evaluated for an LVAD [left ventricular assist device] because when their CRT device is interrogated, it shows 95% pacing. Everyone’s getting ready to put in the LVAD, and we put them on a Holter monitor and guess what? They’re 60% paced. And sometimes you can have dramatic – really dramatic – improvements by just slowing the ventricular response.”

Increasingly, however, he and his fellow electrophysiologists are alternatively turning to atrioventricular junction ablation in suitable candidates for the catheter-based procedure in order to improve their clinical response to CRT.

Dr. Estes cited a study by Columbia University cardiologists as being highly influential in shaping the new understanding of how to use 12-lead Holter monitoring to identify patients with atrial fibrillation who aren’t responding to CRT. They studied 19 patients with permanent atrial fibrillation who were on CRT, all of whom were on beta-blockers, amiodarone, and digoxin for rate control. Although device interrogation showed all 19 patients had in excess of 90% biventricular pacing 12 months after CRT implantation, only 9 patients were actually clinical responders to CRT as defined by at least a 1-grade improvement in New York Heart Association functional class.

Upon wearing an ambulatory 12-lead Holter monitor for 24 hours, only the nine patients with clinical improvement in response to CRT actually had effective pacing; 94% of their heart beats over the course of 24 hours were fully paced, with a mere 2% fusion beats and less than 4% pseudofusion beats. The other 10 patients had an average of only 60% fully paced beats, along with 16% fusion and 24% pseudofusion beats.

The CRT clinical responders also showed evidence of reverse remodeling, with significantly greater improvements in left ventricular ejection fraction, end-systolic dimension, end-diastolic diameter, and end-systolic and end-diastolic volume, compared with nonresponders.

The lesson, according to the investigators, is that the percentage of biventricular pacing, as obtained from CRT device interrogation, is an unreliable indicator of effective pacing in patients with permanent atrial fibrillation. The goal of CRT programming in this population is to try to achieve 100% biventricular capture on the 12-lead Holter monitor (J. Am. Coll. Cardiol. 2009;53:1050-5).

A series of landmark randomized trials has established that in suitable candidates for CRT with NYHA class I through ambulatory class IV heart failure with reduced ejection fraction, the device therapy provides on average about a 17% reduction in all-cause mortality and a 29% decrease in hospitalizations for heart failure above and beyond the benefits obtained through guideline-directed medical therapy. However, the improvements seen in patients with NYHA class I symptoms are less impressive than in those with NYHA class II-IV disease. And it’s possible that the randomized controlled trials overestimate the true benefit from CRT.

“This is a group of extremely experienced investigators who know the literature well. They’re typically quite savvy with patient selection, and they’re vested in getting the right patients into these trials. Unfortunately, there’s not a registry of all eligible patients, so we can’t tell exactly how those patients were selected. It would have been helpful,” Dr. Estes said.

It’s clear from the randomized trials that the ideal patient for CRT is a woman under age 65 with nonischemic cardiomyopathy with a left bundle branch block, normal sinus rhythm, and a QRS duration of 150 milliseconds or more. That’s who’s most likely to obtain clinical benefit from the therapy. The flip side of that is that an older male patient with ischemia, atrial fibrillation, a QRS of 120-150 milliseconds, and non–left bundle branch block is less likely to respond.

“We’ve figured this out. I think we’ve gotten pretty good at giving patients an honest estimate of their probability of responding independent of our ability to get a lead into a good spot in the coronary sinus,” Dr. Estes said. “More than 95% of patients can be adequately resynchronized currently with the tools we have, so it’s not the barrier that it once represented. We have many different techniques available.”

Despite intensive efforts by investigators using sophisticated nuclear studies, echocardiography, and MRI, however, nothing to date has been able to predict who’s going to respond to CRT as well as a simple electrical parameter: the QRS duration.

“It remains really the gold standard. It’s an electrical marker for what is a mechanical event,” Dr. Estes said.

He reported serving as a consultant to Medtronic, St. Jude Medical, and Boston Scientific and receiving research support from Boston Scientific and St. Jude Medical.

bjancin@frontlinemedcom.com