Cardiothoracic

The investigational FORMA system seems safe and may be effective in patients with NYHA Class III/IV heart failure and severe tricuspid valve regurgitation, based on 13 first-in-human cases.

A Canadian surgical team employed the FORMA system (Edwards Lifesciences) as compassionate use therapy for a set of patients with inoperable tricuspid regurgitation. The device was successfully deployed in 12 of the 13 patients, according to data presented at the Transcatheter Cardiovascular Therapeutics annual meeting. There were no deaths or major clinical complications in any of the patients.

A report on seven of these patients was simultaneously published in the Journal of the American College of Cardiology. All of the patients had severe tricuspid regurgitation and heart failure; before surgery, six had a New York Heart Association (NYHA) Functional Classification of III/IV. By 30 days after the procedure, all had improved to NYHA II, wrote Dr. Francisco Campelo-Parada of the Quebec Heart and Lung Institute, the paper’s primary author. Peripheral edema declined and all patients experienced functional improvement, as well.

According to Edwards Lifesciences, the FORMA device uses a foam-filled polymer balloon spacer to reduce tricuspid regurgitation by occupying the regurgitant orifice area and providing a surface for the coaptation of the valve’s native leaflets. Implantation is performed via the left axillary vein.

Patients in the series were a mean of 76 years old. All had severe tricuspid regurgitation. The mean maximal vena contracta was 15.5 mm.

Six had coronary artery disease and five had previously undergone open heart surgery. Additionally, two had previously undergone mitral valve surgery and two had undergone aortic valve surgery. Pulmonary hypertension was present in five. Five patients also had persistent atrial fibrillation. Six had renal insufficiency, with one patient on dialysis. The baseline furosemide dose was 80 mg/day.

All procedures were performed under general sedation and fluoroscopic guidance, with postprocedural positioning checked by cardiac-CT and/or a chest x-ray. The mean postop stay was 4 days.

Tricuspid regurgitation was reduced by at least 1 degree in all patients during the operation; four patients had an immediate 2-degree reduction, reclassifying their regurgitation as mild. Two experienced new-onset atrial fibrillation, and one had several episodes of nonsustained ventricular tachycardia that was managed with beta-blockers.

At the first clinical follow-up 30 days after surgery, all but one patient had an improvement to Class II NYHA status.

Two patients were able to reduce their diuretic dosage; there were no other medication changes. Peripheral edema declined in the entire cohort. Tricuspid regurgitation was graded as moderate in all patients.

There were also associated improvements in quality of life, based on scores on the Kansas City Cardiomyopathy Questionnaire, which increased from 59 before surgery to 86 after surgery. Exercise capacity as measured by the 6-Minute Walk Test improved from 297 meters to 326 meters.

The authors suggested that the 15-mm spacer used in the FORMA device was not well-matched with the mean 15.5-mm vena contracta size in the cohort. Better outcomes might be possible if a larger spacer were available.

“Despite good device positioning, complete coaptation was not achieved, resulting in significant residual degree of postprocedural tricuspid regurgitation,” they said. “Also, the very advanced stage of the disease in most patients may have played a role in the mild reduction at 30 days.”

Despite the rather mild, 1-degree improvement, patients did make considerable improvements in heart failure and functional status. Therefore, the team recommended further study for FORMA, with an eye toward optimizing patient selection.

“Specific criteria for quantifying right ventricular dysfunction and pulmonary hypertension, along with novel quantitative echocardiographic imaging criteria may be required,” they said. “It is conceivable that larger than the currently available spacer sizes may be required to improve echocardiographic results in patients with large noncoaptation defects and vena contracta.”

Dr. Campelo-Parada had no financial disclosures with regard to the device.

[email protected]

The investigational FORMA system seems safe and may be effective in patients with NYHA Class III/IV heart failure and severe tricuspid valve regurgitation, based on 13 first-in-human cases.

A Canadian surgical team employed the FORMA system (Edwards Lifesciences) as compassionate use therapy for a set of patients with inoperable tricuspid regurgitation. The device was successfully deployed in 12 of the 13 patients, according to data presented at the Transcatheter Cardiovascular Therapeutics annual meeting. There were no deaths or major clinical complications in any of the patients.

A report on seven of these patients was simultaneously published in the Journal of the American College of Cardiology. All of the patients had severe tricuspid regurgitation and heart failure; before surgery, six had a New York Heart Association (NYHA) Functional Classification of III/IV. By 30 days after the procedure, all had improved to NYHA II, wrote Dr. Francisco Campelo-Parada of the Quebec Heart and Lung Institute, the paper’s primary author. Peripheral edema declined and all patients experienced functional improvement, as well.

According to Edwards Lifesciences, the FORMA device uses a foam-filled polymer balloon spacer to reduce tricuspid regurgitation by occupying the regurgitant orifice area and providing a surface for the coaptation of the valve’s native leaflets. Implantation is performed via the left axillary vein.

Patients in the series were a mean of 76 years old. All had severe tricuspid regurgitation. The mean maximal vena contracta was 15.5 mm.

Six had coronary artery disease and five had previously undergone open heart surgery. Additionally, two had previously undergone mitral valve surgery and two had undergone aortic valve surgery. Pulmonary hypertension was present in five. Five patients also had persistent atrial fibrillation. Six had renal insufficiency, with one patient on dialysis. The baseline furosemide dose was 80 mg/day.

All procedures were performed under general sedation and fluoroscopic guidance, with postprocedural positioning checked by cardiac-CT and/or a chest x-ray. The mean postop stay was 4 days.

Tricuspid regurgitation was reduced by at least 1 degree in all patients during the operation; four patients had an immediate 2-degree reduction, reclassifying their regurgitation as mild. Two experienced new-onset atrial fibrillation, and one had several episodes of nonsustained ventricular tachycardia that was managed with beta-blockers.

At the first clinical follow-up 30 days after surgery, all but one patient had an improvement to Class II NYHA status.

Two patients were able to reduce their diuretic dosage; there were no other medication changes. Peripheral edema declined in the entire cohort. Tricuspid regurgitation was graded as moderate in all patients.

There were also associated improvements in quality of life, based on scores on the Kansas City Cardiomyopathy Questionnaire, which increased from 59 before surgery to 86 after surgery. Exercise capacity as measured by the 6-Minute Walk Test improved from 297 meters to 326 meters.

The authors suggested that the 15-mm spacer used in the FORMA device was not well-matched with the mean 15.5-mm vena contracta size in the cohort. Better outcomes might be possible if a larger spacer were available.

“Despite good device positioning, complete coaptation was not achieved, resulting in significant residual degree of postprocedural tricuspid regurgitation,” they said. “Also, the very advanced stage of the disease in most patients may have played a role in the mild reduction at 30 days.”

Despite the rather mild, 1-degree improvement, patients did make considerable improvements in heart failure and functional status. Therefore, the team recommended further study for FORMA, with an eye toward optimizing patient selection.

“Specific criteria for quantifying right ventricular dysfunction and pulmonary hypertension, along with novel quantitative echocardiographic imaging criteria may be required,” they said. “It is conceivable that larger than the currently available spacer sizes may be required to improve echocardiographic results in patients with large noncoaptation defects and vena contracta.”

Dr. Campelo-Parada had no financial disclosures with regard to the device.

[email protected]

The investigational FORMA system seems safe and may be effective in patients with NYHA Class III/IV heart failure and severe tricuspid valve regurgitation, based on 13 first-in-human cases.

A Canadian surgical team employed the FORMA system (Edwards Lifesciences) as compassionate use therapy for a set of patients with inoperable tricuspid regurgitation. The device was successfully deployed in 12 of the 13 patients, according to data presented at the Transcatheter Cardiovascular Therapeutics annual meeting. There were no deaths or major clinical complications in any of the patients.

A report on seven of these patients was simultaneously published in the Journal of the American College of Cardiology. All of the patients had severe tricuspid regurgitation and heart failure; before surgery, six had a New York Heart Association (NYHA) Functional Classification of III/IV. By 30 days after the procedure, all had improved to NYHA II, wrote Dr. Francisco Campelo-Parada of the Quebec Heart and Lung Institute, the paper’s primary author. Peripheral edema declined and all patients experienced functional improvement, as well.

According to Edwards Lifesciences, the FORMA device uses a foam-filled polymer balloon spacer to reduce tricuspid regurgitation by occupying the regurgitant orifice area and providing a surface for the coaptation of the valve’s native leaflets. Implantation is performed via the left axillary vein.

Patients in the series were a mean of 76 years old. All had severe tricuspid regurgitation. The mean maximal vena contracta was 15.5 mm.

Six had coronary artery disease and five had previously undergone open heart surgery. Additionally, two had previously undergone mitral valve surgery and two had undergone aortic valve surgery. Pulmonary hypertension was present in five. Five patients also had persistent atrial fibrillation. Six had renal insufficiency, with one patient on dialysis. The baseline furosemide dose was 80 mg/day.

All procedures were performed under general sedation and fluoroscopic guidance, with postprocedural positioning checked by cardiac-CT and/or a chest x-ray. The mean postop stay was 4 days.

Tricuspid regurgitation was reduced by at least 1 degree in all patients during the operation; four patients had an immediate 2-degree reduction, reclassifying their regurgitation as mild. Two experienced new-onset atrial fibrillation, and one had several episodes of nonsustained ventricular tachycardia that was managed with beta-blockers.

At the first clinical follow-up 30 days after surgery, all but one patient had an improvement to Class II NYHA status.

Two patients were able to reduce their diuretic dosage; there were no other medication changes. Peripheral edema declined in the entire cohort. Tricuspid regurgitation was graded as moderate in all patients.

There were also associated improvements in quality of life, based on scores on the Kansas City Cardiomyopathy Questionnaire, which increased from 59 before surgery to 86 after surgery. Exercise capacity as measured by the 6-Minute Walk Test improved from 297 meters to 326 meters.

The authors suggested that the 15-mm spacer used in the FORMA device was not well-matched with the mean 15.5-mm vena contracta size in the cohort. Better outcomes might be possible if a larger spacer were available.

“Despite good device positioning, complete coaptation was not achieved, resulting in significant residual degree of postprocedural tricuspid regurgitation,” they said. “Also, the very advanced stage of the disease in most patients may have played a role in the mild reduction at 30 days.”

Despite the rather mild, 1-degree improvement, patients did make considerable improvements in heart failure and functional status. Therefore, the team recommended further study for FORMA, with an eye toward optimizing patient selection.

“Specific criteria for quantifying right ventricular dysfunction and pulmonary hypertension, along with novel quantitative echocardiographic imaging criteria may be required,” they said. “It is conceivable that larger than the currently available spacer sizes may be required to improve echocardiographic results in patients with large noncoaptation defects and vena contracta.”

Dr. Campelo-Parada had no financial disclosures with regard to the device.

[email protected]

CHICAGO – A few simple baseline variables predict if heart surgery patients will need early nutritional support after their operations, based on a review of more than 1,000 cardiac surgery patients from Johns Hopkins Hospital in Baltimore.

Nonelective surgery and a cardiopulmonary bypass time of 100 minutes or more, plus five preop variables – previous cardiac interventions; total albumin below 4 g/dL; total bilirubin at or above 1.2 mg/dL; white blood cell counts at or above 11,000/mcL; and hematocrit below 27% – predict the need for nutrition in the first few days after cardiac surgery, they found (J Am Coll Surg. 2015 Oct: 221[4];e70).

The Hopkins team has combined those factors into a risk score, with 4 points assigned for low albumin, 6 points for nonelective surgery, 6 points for low hematocrit, and 5 points for the other four variables, yielding a maximum score of 36 points.

The researchers developed the system after discovering that it sometimes took more than a week for cardiac patients who needed postop nutrition to get it. About 40% of patients with scores of 20 or higher will need early nutritional support, and those heart patients are now the ones at Hopkins who get a nutrition consult as soon as they return from the operating room, said Dr. Rika Ohkuma, a general surgery research fellow at Johns Hopkins. “The score can be used for risk stratification and has potential quality improvement implications related to early initiation of nutritional support in high-risk patients.”

Just 2% of patients who score 10 points or below need early nutrition, so consults are less pressing. About 9% of patients who score from 10-20 points will require nutrition, so consults are at the discretion of the physician, the investigators concluded.

Those insights came from a review of 1,056 adult heart cases in 2012. Just 87 patients (8%) had a postop consult for nutritional support. Most wound up with enteral feedings, but they started an average of 5 days after surgery. The handful that needed both parenteral and enteric feedings started them an average of 7 days after surgery.

Meanwhile, those 87 patients had significantly higher hospital mortality (29% vs. 3%), ventilator time (278 vs. 20 hours), and gastrointestinal complications (32% vs. 5%), and fewer discharges to home (49% vs. 84%) than did other patients.

The team thought that the delay in feeding might have had something to do with the poor outcomes, so “we tried to improve our behavior. We know that nutrition is beneficial for critically ill patients and that we need to start early, but there was no gold standard for when to start,” Dr. Ohkuma said.

The investigators came up with the risk score after figuring out how patients who needed nutrition differed from those who did not. They found, for example, that patients who have emergent surgery were more than three times as likely to have a nutrition consult than were those who had elective procedures.

Now when patients are admitted to the ICU after cardiac surgery, “we all know their [nutrition] score; if they are likely to need support, we immediately call the nutritional support service for a consult.” Patients no longer have to wait, Dr. Ohkuma said.

The researchers launched a prospective study in January 2015. Nutritional needs were addressed sooner, at about postop day 4, for the 70 patients who have needed, and mortality seems to be dropping.

The investigators have no relevant disclosures.

[email protected]

CHICAGO – A few simple baseline variables predict if heart surgery patients will need early nutritional support after their operations, based on a review of more than 1,000 cardiac surgery patients from Johns Hopkins Hospital in Baltimore.

Nonelective surgery and a cardiopulmonary bypass time of 100 minutes or more, plus five preop variables – previous cardiac interventions; total albumin below 4 g/dL; total bilirubin at or above 1.2 mg/dL; white blood cell counts at or above 11,000/mcL; and hematocrit below 27% – predict the need for nutrition in the first few days after cardiac surgery, they found (J Am Coll Surg. 2015 Oct: 221[4];e70).

The Hopkins team has combined those factors into a risk score, with 4 points assigned for low albumin, 6 points for nonelective surgery, 6 points for low hematocrit, and 5 points for the other four variables, yielding a maximum score of 36 points.

The researchers developed the system after discovering that it sometimes took more than a week for cardiac patients who needed postop nutrition to get it. About 40% of patients with scores of 20 or higher will need early nutritional support, and those heart patients are now the ones at Hopkins who get a nutrition consult as soon as they return from the operating room, said Dr. Rika Ohkuma, a general surgery research fellow at Johns Hopkins. “The score can be used for risk stratification and has potential quality improvement implications related to early initiation of nutritional support in high-risk patients.”

Just 2% of patients who score 10 points or below need early nutrition, so consults are less pressing. About 9% of patients who score from 10-20 points will require nutrition, so consults are at the discretion of the physician, the investigators concluded.

Those insights came from a review of 1,056 adult heart cases in 2012. Just 87 patients (8%) had a postop consult for nutritional support. Most wound up with enteral feedings, but they started an average of 5 days after surgery. The handful that needed both parenteral and enteric feedings started them an average of 7 days after surgery.

Meanwhile, those 87 patients had significantly higher hospital mortality (29% vs. 3%), ventilator time (278 vs. 20 hours), and gastrointestinal complications (32% vs. 5%), and fewer discharges to home (49% vs. 84%) than did other patients.

The team thought that the delay in feeding might have had something to do with the poor outcomes, so “we tried to improve our behavior. We know that nutrition is beneficial for critically ill patients and that we need to start early, but there was no gold standard for when to start,” Dr. Ohkuma said.

The investigators came up with the risk score after figuring out how patients who needed nutrition differed from those who did not. They found, for example, that patients who have emergent surgery were more than three times as likely to have a nutrition consult than were those who had elective procedures.

Now when patients are admitted to the ICU after cardiac surgery, “we all know their [nutrition] score; if they are likely to need support, we immediately call the nutritional support service for a consult.” Patients no longer have to wait, Dr. Ohkuma said.

The researchers launched a prospective study in January 2015. Nutritional needs were addressed sooner, at about postop day 4, for the 70 patients who have needed, and mortality seems to be dropping.

The investigators have no relevant disclosures.

[email protected]

CHICAGO – A few simple baseline variables predict if heart surgery patients will need early nutritional support after their operations, based on a review of more than 1,000 cardiac surgery patients from Johns Hopkins Hospital in Baltimore.

Nonelective surgery and a cardiopulmonary bypass time of 100 minutes or more, plus five preop variables – previous cardiac interventions; total albumin below 4 g/dL; total bilirubin at or above 1.2 mg/dL; white blood cell counts at or above 11,000/mcL; and hematocrit below 27% – predict the need for nutrition in the first few days after cardiac surgery, they found (J Am Coll Surg. 2015 Oct: 221[4];e70).

The Hopkins team has combined those factors into a risk score, with 4 points assigned for low albumin, 6 points for nonelective surgery, 6 points for low hematocrit, and 5 points for the other four variables, yielding a maximum score of 36 points.

The researchers developed the system after discovering that it sometimes took more than a week for cardiac patients who needed postop nutrition to get it. About 40% of patients with scores of 20 or higher will need early nutritional support, and those heart patients are now the ones at Hopkins who get a nutrition consult as soon as they return from the operating room, said Dr. Rika Ohkuma, a general surgery research fellow at Johns Hopkins. “The score can be used for risk stratification and has potential quality improvement implications related to early initiation of nutritional support in high-risk patients.”

Just 2% of patients who score 10 points or below need early nutrition, so consults are less pressing. About 9% of patients who score from 10-20 points will require nutrition, so consults are at the discretion of the physician, the investigators concluded.

Those insights came from a review of 1,056 adult heart cases in 2012. Just 87 patients (8%) had a postop consult for nutritional support. Most wound up with enteral feedings, but they started an average of 5 days after surgery. The handful that needed both parenteral and enteric feedings started them an average of 7 days after surgery.

Meanwhile, those 87 patients had significantly higher hospital mortality (29% vs. 3%), ventilator time (278 vs. 20 hours), and gastrointestinal complications (32% vs. 5%), and fewer discharges to home (49% vs. 84%) than did other patients.

The team thought that the delay in feeding might have had something to do with the poor outcomes, so “we tried to improve our behavior. We know that nutrition is beneficial for critically ill patients and that we need to start early, but there was no gold standard for when to start,” Dr. Ohkuma said.

The investigators came up with the risk score after figuring out how patients who needed nutrition differed from those who did not. They found, for example, that patients who have emergent surgery were more than three times as likely to have a nutrition consult than were those who had elective procedures.

Now when patients are admitted to the ICU after cardiac surgery, “we all know their [nutrition] score; if they are likely to need support, we immediately call the nutritional support service for a consult.” Patients no longer have to wait, Dr. Ohkuma said.

The researchers launched a prospective study in January 2015. Nutritional needs were addressed sooner, at about postop day 4, for the 70 patients who have needed, and mortality seems to be dropping.

The investigators have no relevant disclosures.

[email protected]

BOSTON – When performing pneumonectomy on patients with benign disease, it is important to be aware of specific preexisting conditions that could complicate surgery before bringing patients into the operating room.

“Sometimes the usual, standard operative procedure is not appropriate, given the circumstances of a particular patient, [and] typically, these pneumonectomies for benign disease are very challenging operations because the inflamed lung is usually quite densely adherent to the inside of the chest cavity,” explained Dr. G. Alex Patterson of Washington University in St. Louis.

In an interview at the Focus on Thoracic Surgery: Technical Challenges and Complications meeting sponsored by the American Association for Thoracic Surgeons, Dr. Patterson talked about the challenges associated with pneumonectomies for benign disease and how surgeons can safely navigate them.

Dr. Patterson had no relevant disclosures.

[email protected]

BOSTON – When performing pneumonectomy on patients with benign disease, it is important to be aware of specific preexisting conditions that could complicate surgery before bringing patients into the operating room.

“Sometimes the usual, standard operative procedure is not appropriate, given the circumstances of a particular patient, [and] typically, these pneumonectomies for benign disease are very challenging operations because the inflamed lung is usually quite densely adherent to the inside of the chest cavity,” explained Dr. G. Alex Patterson of Washington University in St. Louis.

In an interview at the Focus on Thoracic Surgery: Technical Challenges and Complications meeting sponsored by the American Association for Thoracic Surgeons, Dr. Patterson talked about the challenges associated with pneumonectomies for benign disease and how surgeons can safely navigate them.

Dr. Patterson had no relevant disclosures.

[email protected]

BOSTON – When performing pneumonectomy on patients with benign disease, it is important to be aware of specific preexisting conditions that could complicate surgery before bringing patients into the operating room.

“Sometimes the usual, standard operative procedure is not appropriate, given the circumstances of a particular patient, [and] typically, these pneumonectomies for benign disease are very challenging operations because the inflamed lung is usually quite densely adherent to the inside of the chest cavity,” explained Dr. G. Alex Patterson of Washington University in St. Louis.

In an interview at the Focus on Thoracic Surgery: Technical Challenges and Complications meeting sponsored by the American Association for Thoracic Surgeons, Dr. Patterson talked about the challenges associated with pneumonectomies for benign disease and how surgeons can safely navigate them.

Dr. Patterson had no relevant disclosures.

[email protected]

BOSTON – When it comes to intraoperative complications during thoracoscopic lobectomy, the mantra for success is to always have a preoperative plan, but be flexible enough to improvise should anything out of the norm arise.

“Many surgeons, when they ask [me] about this specific topic, ask what specific tricks [I] have, but I don’t like to use the word ‘trick’ [because] it’s not something we can do that other people can’t,” explained Dr. Thomas A. D’Amico, chief of general thoracic surgery at Duke University in Durham, North Carolina.

“It’s really just about strategy – how you start an operation, what the conduct of it should be, and when you see things that are less common or more difficult cases, how you think about those and manage those.”

In an interview at the Focus on Thoracic Surgery: Technical Challenges and Complications meeting held by the American Association for Thoracic Surgeons, Dr. D’Amico talked about why surgeons around the world are apprehensive about thoracoscopic lobectomy and why it’s important to begin training residents on how to properly perform the procedure as soon as possible, as it helps mitigate uncertainty while giving them valuable experience to solve any issues that may come up during an operation.

Dr. D’Amico disclosed that he is a consultant for Scanlan, but that it is not relevant to this discussion.

[email protected]

BOSTON – When it comes to intraoperative complications during thoracoscopic lobectomy, the mantra for success is to always have a preoperative plan, but be flexible enough to improvise should anything out of the norm arise.

“Many surgeons, when they ask [me] about this specific topic, ask what specific tricks [I] have, but I don’t like to use the word ‘trick’ [because] it’s not something we can do that other people can’t,” explained Dr. Thomas A. D’Amico, chief of general thoracic surgery at Duke University in Durham, North Carolina.

“It’s really just about strategy – how you start an operation, what the conduct of it should be, and when you see things that are less common or more difficult cases, how you think about those and manage those.”

In an interview at the Focus on Thoracic Surgery: Technical Challenges and Complications meeting held by the American Association for Thoracic Surgeons, Dr. D’Amico talked about why surgeons around the world are apprehensive about thoracoscopic lobectomy and why it’s important to begin training residents on how to properly perform the procedure as soon as possible, as it helps mitigate uncertainty while giving them valuable experience to solve any issues that may come up during an operation.

Dr. D’Amico disclosed that he is a consultant for Scanlan, but that it is not relevant to this discussion.

[email protected]

BOSTON – When it comes to intraoperative complications during thoracoscopic lobectomy, the mantra for success is to always have a preoperative plan, but be flexible enough to improvise should anything out of the norm arise.

“Many surgeons, when they ask [me] about this specific topic, ask what specific tricks [I] have, but I don’t like to use the word ‘trick’ [because] it’s not something we can do that other people can’t,” explained Dr. Thomas A. D’Amico, chief of general thoracic surgery at Duke University in Durham, North Carolina.

“It’s really just about strategy – how you start an operation, what the conduct of it should be, and when you see things that are less common or more difficult cases, how you think about those and manage those.”

In an interview at the Focus on Thoracic Surgery: Technical Challenges and Complications meeting held by the American Association for Thoracic Surgeons, Dr. D’Amico talked about why surgeons around the world are apprehensive about thoracoscopic lobectomy and why it’s important to begin training residents on how to properly perform the procedure as soon as possible, as it helps mitigate uncertainty while giving them valuable experience to solve any issues that may come up during an operation.

Dr. D’Amico disclosed that he is a consultant for Scanlan, but that it is not relevant to this discussion.

[email protected]

Injections of botulinum toxin into epicardial fat pads during cardiac surgery may provide long-term suppression of atrial fibrillation, according to results from a randomized, placebo-controlled trial published Oct. 20.

Sixty patients with a history of atrial fibrillation, who were undergoing coronary artery bypass graft surgery, were randomized to an injection of botulinum toxin or saline into each epicardial fat pad during surgery.

©luiscar/Thinkstockphotos.com

Data from 12 months of monitoring via an implantable loop recorder showed patients who received the botulinum toxin injections had a significantly reduced incidence of atrial fibrillation, compared with the placebo group in the 30 days after surgery (7% vs. 30%, P = .024) and at 12 months (0% vs. 27%, P = .002).

Both groups showed significant decreases in heart rate variability after surgery, but at 3 months, these had largely recovered in the placebo group and remained depressed in the botulinum toxin group until 6 months (Circ Arrhythm Electrophysiol. 2015 Oct 20. doi: 10.1161/CIRCEP.115.003199).

No patients in the botulinum group developed persistent atrial fibrillation or required antiarrhythmic therapy or interventions, and there were no significant differences between the two groups in other outcomes such as hospital length of stay or postoperative complications.

“The blocking effects are temporary and recover in 1 to 6 months, depending on the injection site [but] for patients with a high short-term risk of postoperative AF after cardiac surgery, temporary suppression of AF without any destruction of the anatomic structures is clinically desirable,” wrote Dr. Evgeny Pokushalov of State Research Institute of Circulation Pathology, Novosibirsk, Russia, and coauthors.

No conflicts of interest were declared.

Injections of botulinum toxin into epicardial fat pads during cardiac surgery may provide long-term suppression of atrial fibrillation, according to results from a randomized, placebo-controlled trial published Oct. 20.

Sixty patients with a history of atrial fibrillation, who were undergoing coronary artery bypass graft surgery, were randomized to an injection of botulinum toxin or saline into each epicardial fat pad during surgery.

©luiscar/Thinkstockphotos.com

Data from 12 months of monitoring via an implantable loop recorder showed patients who received the botulinum toxin injections had a significantly reduced incidence of atrial fibrillation, compared with the placebo group in the 30 days after surgery (7% vs. 30%, P = .024) and at 12 months (0% vs. 27%, P = .002).

Both groups showed significant decreases in heart rate variability after surgery, but at 3 months, these had largely recovered in the placebo group and remained depressed in the botulinum toxin group until 6 months (Circ Arrhythm Electrophysiol. 2015 Oct 20. doi: 10.1161/CIRCEP.115.003199).

No patients in the botulinum group developed persistent atrial fibrillation or required antiarrhythmic therapy or interventions, and there were no significant differences between the two groups in other outcomes such as hospital length of stay or postoperative complications.

“The blocking effects are temporary and recover in 1 to 6 months, depending on the injection site [but] for patients with a high short-term risk of postoperative AF after cardiac surgery, temporary suppression of AF without any destruction of the anatomic structures is clinically desirable,” wrote Dr. Evgeny Pokushalov of State Research Institute of Circulation Pathology, Novosibirsk, Russia, and coauthors.

No conflicts of interest were declared.

Injections of botulinum toxin into epicardial fat pads during cardiac surgery may provide long-term suppression of atrial fibrillation, according to results from a randomized, placebo-controlled trial published Oct. 20.

Sixty patients with a history of atrial fibrillation, who were undergoing coronary artery bypass graft surgery, were randomized to an injection of botulinum toxin or saline into each epicardial fat pad during surgery.

©luiscar/Thinkstockphotos.com

Data from 12 months of monitoring via an implantable loop recorder showed patients who received the botulinum toxin injections had a significantly reduced incidence of atrial fibrillation, compared with the placebo group in the 30 days after surgery (7% vs. 30%, P = .024) and at 12 months (0% vs. 27%, P = .002).

Both groups showed significant decreases in heart rate variability after surgery, but at 3 months, these had largely recovered in the placebo group and remained depressed in the botulinum toxin group until 6 months (Circ Arrhythm Electrophysiol. 2015 Oct 20. doi: 10.1161/CIRCEP.115.003199).

No patients in the botulinum group developed persistent atrial fibrillation or required antiarrhythmic therapy or interventions, and there were no significant differences between the two groups in other outcomes such as hospital length of stay or postoperative complications.

“The blocking effects are temporary and recover in 1 to 6 months, depending on the injection site [but] for patients with a high short-term risk of postoperative AF after cardiac surgery, temporary suppression of AF without any destruction of the anatomic structures is clinically desirable,” wrote Dr. Evgeny Pokushalov of State Research Institute of Circulation Pathology, Novosibirsk, Russia, and coauthors.

No conflicts of interest were declared.

SAN FRANCISCO – Everolimus-eluting stents were more effective than were paclitaxel-eluting stents in diabetes patients with coronary artery disease who underwent percutaneous coronary intervention (PCI) in the randomized, multicenter TUXEDO-India trial.

The everolimus-eluting stents were shown to be superior to paclitaxel-eluting stents on several endpoints, including target-vessel failure, myocardial infarction, and stent thrombosis at 1 year Dr. Upendra Kaul reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

Target vessel failure – the study’s primary endpoint, defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization – occurred in 5.6% of 914 patients randomized to the paclitaxel-eluting stent group, compared with 2.9% of 916 randomized to the everolimus-eluting stent group (relative risk, 1.89), Dr. Kaul of Fortis Escorts Heart Institute, New Delhi, reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.

The rate of spontaneous MI was 3.2% vs. 1.2% in the groups, respectively, and the rate of stent thrombosis was 2.1% vs. 0.4%. Target-vessel revascularization and target-lesion revascularization rates in both groups were 3.4% vs. 1.2% with paclitaxel- and everolimus-eluting stents, respectively, he said, noting that the superiority of everolimus-eluting stents was maintained in insulin-requiring patients.

The findings, which were published online simultaneously (N Engl J Med. 2015 Oct. 14;doi: 10.1056/NEJMoa1510188), effectively end the debate regarding whether paclitaxel-eluting stents are the better choice in diabetes patients with coronary artery disease.

Paclitaxel-eluting stents are generally accepted to be inferior to limus-eluting stents in most patients, but data from numerous trials have been conflicting as to whether that is true in diabetes patients.

“In the absence of a dedicated adequately powered study, a definitive answer is not possible,” Dr. Kaul said.

The findings from TUXEDO, the largest trial to compare paclitaxel- and everolimus-eluting stents head to head in diabetes patients, support “the current worldwide practice of use of new-generation limus-eluting stents, even in patients with insulin-requiring diabetes,” he said.

The findings raise questions about the results of prior coronary artery bypass grafting vs. stenting trials that show superiority of CABG, because first-generation stents, which are inferior to everolimus-eluting stents, were used as comparators in those trials, he noted.

Indeed, current guidelines for bypass surgery and PCI are based upon the findings of those trials, and while the TUXEDO findings don’t invalidate those prior studies, they do raise questions about whether the differences in favor of bypass surgery are much smaller than believed in the setting of modern stent use, commented Dr. Bernard J. Gersh of the Mayo Clinic, Rochester, Minn.

The TUXEDO-India trial was supported by Boston Scientific.

[email protected]

SAN FRANCISCO – Everolimus-eluting stents were more effective than were paclitaxel-eluting stents in diabetes patients with coronary artery disease who underwent percutaneous coronary intervention (PCI) in the randomized, multicenter TUXEDO-India trial.

The everolimus-eluting stents were shown to be superior to paclitaxel-eluting stents on several endpoints, including target-vessel failure, myocardial infarction, and stent thrombosis at 1 year Dr. Upendra Kaul reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

Target vessel failure – the study’s primary endpoint, defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization – occurred in 5.6% of 914 patients randomized to the paclitaxel-eluting stent group, compared with 2.9% of 916 randomized to the everolimus-eluting stent group (relative risk, 1.89), Dr. Kaul of Fortis Escorts Heart Institute, New Delhi, reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.

The rate of spontaneous MI was 3.2% vs. 1.2% in the groups, respectively, and the rate of stent thrombosis was 2.1% vs. 0.4%. Target-vessel revascularization and target-lesion revascularization rates in both groups were 3.4% vs. 1.2% with paclitaxel- and everolimus-eluting stents, respectively, he said, noting that the superiority of everolimus-eluting stents was maintained in insulin-requiring patients.

The findings, which were published online simultaneously (N Engl J Med. 2015 Oct. 14;doi: 10.1056/NEJMoa1510188), effectively end the debate regarding whether paclitaxel-eluting stents are the better choice in diabetes patients with coronary artery disease.

Paclitaxel-eluting stents are generally accepted to be inferior to limus-eluting stents in most patients, but data from numerous trials have been conflicting as to whether that is true in diabetes patients.

“In the absence of a dedicated adequately powered study, a definitive answer is not possible,” Dr. Kaul said.

The findings from TUXEDO, the largest trial to compare paclitaxel- and everolimus-eluting stents head to head in diabetes patients, support “the current worldwide practice of use of new-generation limus-eluting stents, even in patients with insulin-requiring diabetes,” he said.

The findings raise questions about the results of prior coronary artery bypass grafting vs. stenting trials that show superiority of CABG, because first-generation stents, which are inferior to everolimus-eluting stents, were used as comparators in those trials, he noted.

Indeed, current guidelines for bypass surgery and PCI are based upon the findings of those trials, and while the TUXEDO findings don’t invalidate those prior studies, they do raise questions about whether the differences in favor of bypass surgery are much smaller than believed in the setting of modern stent use, commented Dr. Bernard J. Gersh of the Mayo Clinic, Rochester, Minn.

The TUXEDO-India trial was supported by Boston Scientific.

[email protected]

SAN FRANCISCO – Everolimus-eluting stents were more effective than were paclitaxel-eluting stents in diabetes patients with coronary artery disease who underwent percutaneous coronary intervention (PCI) in the randomized, multicenter TUXEDO-India trial.

The everolimus-eluting stents were shown to be superior to paclitaxel-eluting stents on several endpoints, including target-vessel failure, myocardial infarction, and stent thrombosis at 1 year Dr. Upendra Kaul reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

Target vessel failure – the study’s primary endpoint, defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization – occurred in 5.6% of 914 patients randomized to the paclitaxel-eluting stent group, compared with 2.9% of 916 randomized to the everolimus-eluting stent group (relative risk, 1.89), Dr. Kaul of Fortis Escorts Heart Institute, New Delhi, reported at the meeting, which was sponsored by the Cardiovascular Research Foundation.

The rate of spontaneous MI was 3.2% vs. 1.2% in the groups, respectively, and the rate of stent thrombosis was 2.1% vs. 0.4%. Target-vessel revascularization and target-lesion revascularization rates in both groups were 3.4% vs. 1.2% with paclitaxel- and everolimus-eluting stents, respectively, he said, noting that the superiority of everolimus-eluting stents was maintained in insulin-requiring patients.

The findings, which were published online simultaneously (N Engl J Med. 2015 Oct. 14;doi: 10.1056/NEJMoa1510188), effectively end the debate regarding whether paclitaxel-eluting stents are the better choice in diabetes patients with coronary artery disease.

Paclitaxel-eluting stents are generally accepted to be inferior to limus-eluting stents in most patients, but data from numerous trials have been conflicting as to whether that is true in diabetes patients.

“In the absence of a dedicated adequately powered study, a definitive answer is not possible,” Dr. Kaul said.

The findings from TUXEDO, the largest trial to compare paclitaxel- and everolimus-eluting stents head to head in diabetes patients, support “the current worldwide practice of use of new-generation limus-eluting stents, even in patients with insulin-requiring diabetes,” he said.

The findings raise questions about the results of prior coronary artery bypass grafting vs. stenting trials that show superiority of CABG, because first-generation stents, which are inferior to everolimus-eluting stents, were used as comparators in those trials, he noted.

Indeed, current guidelines for bypass surgery and PCI are based upon the findings of those trials, and while the TUXEDO findings don’t invalidate those prior studies, they do raise questions about whether the differences in favor of bypass surgery are much smaller than believed in the setting of modern stent use, commented Dr. Bernard J. Gersh of the Mayo Clinic, Rochester, Minn.

The TUXEDO-India trial was supported by Boston Scientific.

[email protected]

SAN FRANCISCO – Access site made no difference in major adverse events 1 year after percutaneous coronary intervention in patients randomized to transradial or transfemoral access, in a study of more than 1,700 Chinese patients.

The DRAGON trial (Determination of the Radial vs. Groin Coronary Angioplasty) also showed that the two types of access had virtually identical rates of bleeding complications a week after the intervention.

“This was an incredible study,” Dr. Roxana Mehran

At 25 surgery sites across China, patients who presented with the need for ad hoc percutaneous coronary intervention (PCI) were randomly assigned in a 2:1 fashion to have transradial or transfemoral access. In all, 1,212 PCI patients had transradial catheterization, while 527 were given transfemoral PCI. After 1 year, patients in both groups were found to have nearly identical major adverse cardiac or cerebrovascular event–free (MACCE-free) rates: 95.8% for transradial access vs. 95.5% for transfemoral access (P for noninferiority, less than .001). Bleeding complication rates at 7 days were also similar: 99.9% of patients who’d received transradial PCI were free of any access site bleeding event, as were 99.0% of all transfemoral PCI patients (P for superiority, less than .001). Nearly half of patients in the transfemoral access group also received a hemostatic intervention, and 40% of all patients required anticoagulation therapy, Dr. Shigeru Saito reported at the meeting, sponsored by the Cardiovascular Research Foundation.

While transradial access’s noninferiority to rates of site complications in transfemoral access is already supported in the literature, Dr. Saito, director of cardiology and catheterization laboratories at Shonan Kamakura General Hospital, Kanagawa, Japan, said he and his colleagues wanted to establish transradial PCI’s long-term efficacy so that it could become the standard internationally, unless the patient’s situation dictates otherwise.

Transradial access is considered routine in much of Asia and Europe, but in the United States, fewer than 20% of interventionalists currently use it, said Dr. Daniel I. Simon.

“[Radial access] is certainly increasing, but ... what I would hate to see happen is for our fellows and trainees to lose the femoral techniques that you need for some cases,” said Dr. Simon, professor of medicine at Case Western Reserve University, Cleveland. “Certainly, femoral access will be required for some procedures, but you can make the case for ST-segment elevation MI that transradial access should really be the standard, because that’s where the data is the most robust.” Dr. Simon was not involved in the study.

Dr. Saito, Dr. Mehran, and Dr. Simon had no relevant disclosures.

[email protected]

On Twitter @whitneymcknight

SAN FRANCISCO – Access site made no difference in major adverse events 1 year after percutaneous coronary intervention in patients randomized to transradial or transfemoral access, in a study of more than 1,700 Chinese patients.

The DRAGON trial (Determination of the Radial vs. Groin Coronary Angioplasty) also showed that the two types of access had virtually identical rates of bleeding complications a week after the intervention.

“This was an incredible study,” Dr. Roxana Mehran

At 25 surgery sites across China, patients who presented with the need for ad hoc percutaneous coronary intervention (PCI) were randomly assigned in a 2:1 fashion to have transradial or transfemoral access. In all, 1,212 PCI patients had transradial catheterization, while 527 were given transfemoral PCI. After 1 year, patients in both groups were found to have nearly identical major adverse cardiac or cerebrovascular event–free (MACCE-free) rates: 95.8% for transradial access vs. 95.5% for transfemoral access (P for noninferiority, less than .001). Bleeding complication rates at 7 days were also similar: 99.9% of patients who’d received transradial PCI were free of any access site bleeding event, as were 99.0% of all transfemoral PCI patients (P for superiority, less than .001). Nearly half of patients in the transfemoral access group also received a hemostatic intervention, and 40% of all patients required anticoagulation therapy, Dr. Shigeru Saito reported at the meeting, sponsored by the Cardiovascular Research Foundation.

While transradial access’s noninferiority to rates of site complications in transfemoral access is already supported in the literature, Dr. Saito, director of cardiology and catheterization laboratories at Shonan Kamakura General Hospital, Kanagawa, Japan, said he and his colleagues wanted to establish transradial PCI’s long-term efficacy so that it could become the standard internationally, unless the patient’s situation dictates otherwise.

Transradial access is considered routine in much of Asia and Europe, but in the United States, fewer than 20% of interventionalists currently use it, said Dr. Daniel I. Simon.

“[Radial access] is certainly increasing, but ... what I would hate to see happen is for our fellows and trainees to lose the femoral techniques that you need for some cases,” said Dr. Simon, professor of medicine at Case Western Reserve University, Cleveland. “Certainly, femoral access will be required for some procedures, but you can make the case for ST-segment elevation MI that transradial access should really be the standard, because that’s where the data is the most robust.” Dr. Simon was not involved in the study.

Dr. Saito, Dr. Mehran, and Dr. Simon had no relevant disclosures.

[email protected]

On Twitter @whitneymcknight

SAN FRANCISCO – Access site made no difference in major adverse events 1 year after percutaneous coronary intervention in patients randomized to transradial or transfemoral access, in a study of more than 1,700 Chinese patients.

The DRAGON trial (Determination of the Radial vs. Groin Coronary Angioplasty) also showed that the two types of access had virtually identical rates of bleeding complications a week after the intervention.

“This was an incredible study,” Dr. Roxana Mehran

At 25 surgery sites across China, patients who presented with the need for ad hoc percutaneous coronary intervention (PCI) were randomly assigned in a 2:1 fashion to have transradial or transfemoral access. In all, 1,212 PCI patients had transradial catheterization, while 527 were given transfemoral PCI. After 1 year, patients in both groups were found to have nearly identical major adverse cardiac or cerebrovascular event–free (MACCE-free) rates: 95.8% for transradial access vs. 95.5% for transfemoral access (P for noninferiority, less than .001). Bleeding complication rates at 7 days were also similar: 99.9% of patients who’d received transradial PCI were free of any access site bleeding event, as were 99.0% of all transfemoral PCI patients (P for superiority, less than .001). Nearly half of patients in the transfemoral access group also received a hemostatic intervention, and 40% of all patients required anticoagulation therapy, Dr. Shigeru Saito reported at the meeting, sponsored by the Cardiovascular Research Foundation.

While transradial access’s noninferiority to rates of site complications in transfemoral access is already supported in the literature, Dr. Saito, director of cardiology and catheterization laboratories at Shonan Kamakura General Hospital, Kanagawa, Japan, said he and his colleagues wanted to establish transradial PCI’s long-term efficacy so that it could become the standard internationally, unless the patient’s situation dictates otherwise.

Transradial access is considered routine in much of Asia and Europe, but in the United States, fewer than 20% of interventionalists currently use it, said Dr. Daniel I. Simon.

“[Radial access] is certainly increasing, but ... what I would hate to see happen is for our fellows and trainees to lose the femoral techniques that you need for some cases,” said Dr. Simon, professor of medicine at Case Western Reserve University, Cleveland. “Certainly, femoral access will be required for some procedures, but you can make the case for ST-segment elevation MI that transradial access should really be the standard, because that’s where the data is the most robust.” Dr. Simon was not involved in the study.

Dr. Saito, Dr. Mehran, and Dr. Simon had no relevant disclosures.

[email protected]

On Twitter @whitneymcknight

SAN FRANCISCO – Implantation of the novel DREAMS 2G sirolimus-eluting absorbable metal scaffold in patients with de novo coronary lesions was feasible and had favorable safety and performance outcomes at 6 months in the BIOSOLVE-II trial.

The findings of the prospective, nonrandomized, first-in-human trial suggest that the DREAMS 2G device – made from magnesium alloy with an absorption time of 12 months – could serve as an alternative to absorbable polymeric scaffolds for the treatment of obstructive coronary disease, Dr. Michael Haude of Medical Clinic I, Städtische Kliniken Neuss, Germany, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

In 120 patients with coronary target lesions who completed the trial and follow-up, the mean in-segment late lumen loss at 6 months – the primary endpoint of the study – was 0.27 mm, and in-scaffold late lumen loss was 0.44 mm. Discernable vasomotion was documented in 80% of a subgroup of 25 patients, he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Among patients who underwent additional assessment, intravascular ultrasound showed preservation of the scaffold area (mean of 6.24 mm² post procedure vs. 6.21 mm² at 6 months) with a low mean neointimal area (0.08 mm²). No intraluminal mass was detected on optical coherence tomography, he noted.

Four patients (3%) experienced target lesion failure, and one died from cardiac death.

Periprocedural myocardial infarction occurred in one patient, and clinically driven target lesion revascularization was required in two patients (1.7%).

No definite or probable scaffold thrombosis was observed, Dr. Haude said.

Study subjects were enrolled during October 2013–May 2015 at centers in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. All had stable or unstable angina or documented silent ischemia and no more than two de novo lesions with a reference vessel diameter between 2.2 and 3.7 mm. The results were published online concurrently with Dr. Haude’s presentation (Lancet. 2015 Oct 12. doi:10.1016/S0140-6736[15]00447-X)

The findings demonstrate improved lumen loss with the DREAMS 2G device, compared with precursor devices, he said.

“If we compare this to the data that we have for the previous version, the bare version of the magnesium absorbable scaffold, the in-segment lumen loss was 0.83. That went down by 37% to the version with the paclitaxel elusion at 0.52, and then it decreased again by 48% to 0.27 ... without a single stent thrombosis case,” he said.

Absorbable metal scaffolds offer good radial strength, low acute recoil, and high compliance to the vessel geometry. Also, they can be implanted via a single step inflation, and thus can be implanted in a way similar to that of a permanent metal stent, he noted.

They can also be electropolished, which provides softer, round edges that allow for improved trackability and deliverability, he said, noting that the magnesium alloy stent provides the strength of metal, but also provides a potential long-term benefit with its ability to be absorbed over time.

Though limited by the nonrandomized trial design and lack of direct comparison with other permanent stents or scaffolds, as well as by the inclusion of only patients with straightforward de novo lesions and uncertainty about ideal follow-up time, DREAMS 2G offers a potential alternative to polymeric absorbable scaffolds, which are currently the scaffolds that are commercially available , Dr. Haude said.

BIOSOLVE-II was funded by Biotronik AG. Dr. Haude received study grants and lecture fees from Biotronik, Abbott Vascular, Cardiac dimensions, Medtronic, Volcano, and Lilly, as well as consulting fees/honoraria from Biotronik AG.

[email protected]

SAN FRANCISCO – Implantation of the novel DREAMS 2G sirolimus-eluting absorbable metal scaffold in patients with de novo coronary lesions was feasible and had favorable safety and performance outcomes at 6 months in the BIOSOLVE-II trial.

The findings of the prospective, nonrandomized, first-in-human trial suggest that the DREAMS 2G device – made from magnesium alloy with an absorption time of 12 months – could serve as an alternative to absorbable polymeric scaffolds for the treatment of obstructive coronary disease, Dr. Michael Haude of Medical Clinic I, Städtische Kliniken Neuss, Germany, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

In 120 patients with coronary target lesions who completed the trial and follow-up, the mean in-segment late lumen loss at 6 months – the primary endpoint of the study – was 0.27 mm, and in-scaffold late lumen loss was 0.44 mm. Discernable vasomotion was documented in 80% of a subgroup of 25 patients, he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Among patients who underwent additional assessment, intravascular ultrasound showed preservation of the scaffold area (mean of 6.24 mm² post procedure vs. 6.21 mm² at 6 months) with a low mean neointimal area (0.08 mm²). No intraluminal mass was detected on optical coherence tomography, he noted.

Four patients (3%) experienced target lesion failure, and one died from cardiac death.

Periprocedural myocardial infarction occurred in one patient, and clinically driven target lesion revascularization was required in two patients (1.7%).

No definite or probable scaffold thrombosis was observed, Dr. Haude said.

Study subjects were enrolled during October 2013–May 2015 at centers in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. All had stable or unstable angina or documented silent ischemia and no more than two de novo lesions with a reference vessel diameter between 2.2 and 3.7 mm. The results were published online concurrently with Dr. Haude’s presentation (Lancet. 2015 Oct 12. doi:10.1016/S0140-6736[15]00447-X)

The findings demonstrate improved lumen loss with the DREAMS 2G device, compared with precursor devices, he said.

“If we compare this to the data that we have for the previous version, the bare version of the magnesium absorbable scaffold, the in-segment lumen loss was 0.83. That went down by 37% to the version with the paclitaxel elusion at 0.52, and then it decreased again by 48% to 0.27 ... without a single stent thrombosis case,” he said.

Absorbable metal scaffolds offer good radial strength, low acute recoil, and high compliance to the vessel geometry. Also, they can be implanted via a single step inflation, and thus can be implanted in a way similar to that of a permanent metal stent, he noted.

They can also be electropolished, which provides softer, round edges that allow for improved trackability and deliverability, he said, noting that the magnesium alloy stent provides the strength of metal, but also provides a potential long-term benefit with its ability to be absorbed over time.

Though limited by the nonrandomized trial design and lack of direct comparison with other permanent stents or scaffolds, as well as by the inclusion of only patients with straightforward de novo lesions and uncertainty about ideal follow-up time, DREAMS 2G offers a potential alternative to polymeric absorbable scaffolds, which are currently the scaffolds that are commercially available , Dr. Haude said.

BIOSOLVE-II was funded by Biotronik AG. Dr. Haude received study grants and lecture fees from Biotronik, Abbott Vascular, Cardiac dimensions, Medtronic, Volcano, and Lilly, as well as consulting fees/honoraria from Biotronik AG.

[email protected]

SAN FRANCISCO – Implantation of the novel DREAMS 2G sirolimus-eluting absorbable metal scaffold in patients with de novo coronary lesions was feasible and had favorable safety and performance outcomes at 6 months in the BIOSOLVE-II trial.

The findings of the prospective, nonrandomized, first-in-human trial suggest that the DREAMS 2G device – made from magnesium alloy with an absorption time of 12 months – could serve as an alternative to absorbable polymeric scaffolds for the treatment of obstructive coronary disease, Dr. Michael Haude of Medical Clinic I, Städtische Kliniken Neuss, Germany, reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

In 120 patients with coronary target lesions who completed the trial and follow-up, the mean in-segment late lumen loss at 6 months – the primary endpoint of the study – was 0.27 mm, and in-scaffold late lumen loss was 0.44 mm. Discernable vasomotion was documented in 80% of a subgroup of 25 patients, he said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

Among patients who underwent additional assessment, intravascular ultrasound showed preservation of the scaffold area (mean of 6.24 mm² post procedure vs. 6.21 mm² at 6 months) with a low mean neointimal area (0.08 mm²). No intraluminal mass was detected on optical coherence tomography, he noted.

Four patients (3%) experienced target lesion failure, and one died from cardiac death.

Periprocedural myocardial infarction occurred in one patient, and clinically driven target lesion revascularization was required in two patients (1.7%).

No definite or probable scaffold thrombosis was observed, Dr. Haude said.

Study subjects were enrolled during October 2013–May 2015 at centers in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. All had stable or unstable angina or documented silent ischemia and no more than two de novo lesions with a reference vessel diameter between 2.2 and 3.7 mm. The results were published online concurrently with Dr. Haude’s presentation (Lancet. 2015 Oct 12. doi:10.1016/S0140-6736[15]00447-X)

The findings demonstrate improved lumen loss with the DREAMS 2G device, compared with precursor devices, he said.

“If we compare this to the data that we have for the previous version, the bare version of the magnesium absorbable scaffold, the in-segment lumen loss was 0.83. That went down by 37% to the version with the paclitaxel elusion at 0.52, and then it decreased again by 48% to 0.27 ... without a single stent thrombosis case,” he said.

Absorbable metal scaffolds offer good radial strength, low acute recoil, and high compliance to the vessel geometry. Also, they can be implanted via a single step inflation, and thus can be implanted in a way similar to that of a permanent metal stent, he noted.

They can also be electropolished, which provides softer, round edges that allow for improved trackability and deliverability, he said, noting that the magnesium alloy stent provides the strength of metal, but also provides a potential long-term benefit with its ability to be absorbed over time.

Though limited by the nonrandomized trial design and lack of direct comparison with other permanent stents or scaffolds, as well as by the inclusion of only patients with straightforward de novo lesions and uncertainty about ideal follow-up time, DREAMS 2G offers a potential alternative to polymeric absorbable scaffolds, which are currently the scaffolds that are commercially available , Dr. Haude said.

BIOSOLVE-II was funded by Biotronik AG. Dr. Haude received study grants and lecture fees from Biotronik, Abbott Vascular, Cardiac dimensions, Medtronic, Volcano, and Lilly, as well as consulting fees/honoraria from Biotronik AG.

[email protected]

The Watchman device, approved for routine use by the Food and Drug Administration in March, gives U.S. atrial fibrillation patients their first alternative to chronic anticoagulant treatment for preventing ischemic stroke.

By closing off the sac-like left-atrial appendage (LAA) with Watchman – a plug-like device placed via percutaneous, transcatheter delivery – blood clots cannot form in the LAA, thereby eliminating the source for most of the thrombi that threaten to cause ischemic strokes in patients with atrial fibrillation (AF).

But while many cardiologists welcome this new option that, for the first time, gives AF patients a way to avoid years or even decades of daily treatment with an anticoagulant, U.S. rollout of the device out has not been seamless. In many regions, health insurers have been unwilling to cover payment for Watchman and its placement, say physicians. Medicare AF patients in particular have been in a state of limbo for receiving a Watchman device while the Centers for Medicare and Medicaid Services (CMS) makes a national coverage determination, a decision not expected until later this year.

In addition, the AF patients who arguably are the best candidates for receiving this device are technically ineligible based on Watchman’s labeling as well as a very limited evidence base. The FDA approved the device specifically for patients judged “suitable for warfarin,” a decision driven largely by the two Watchman trials that led to approval. Each of these trials randomized warfarin-eligible patients either to receive the device along with a 6-week course of warfarin following placement to ensure against acute thromboembolic complications, or to chronic warfarin treatment with no device.

Although this design allowed head-to-head comparison between Watchman and the traditional standard for anticoagulation in AF patients, it left unaddressed the question of how Watchman performs in the AF patient population with the most obvious indication for a mechanical solution to stroke risk: patients who are completely intolerant of anticoagulation treatment. By strict labeling criteria those patients, desperate for an effective means to reduce their stroke risk, are ineligible to receive Watchman.

“It’s approved for patients who can take warfarin, and that’s wrong,” said Dr. Peter R. Kowey, an AF specialist and professor and director of the Center for Clinical Cardiology at the Lankenau Institute for Medical Research in Wynnewood, Pa. “Most of us in clinical practice believe Watchman has the potential to help patients who would be difficult to anticoagulate long term. This is how it’s used around the world.”

Who should get Watchman right now?

With patients with contraindications for anticoagulants excluded by current labeling, who are the right patients to get this device, especially with long-term experience still relatively limited? Many AF experts say they currently see targeting it to AF patients who are clearly at high risk from both stroke and anticoagulation, as well as possibly also patients who face less of a risk from an anticoagulant treatment but express a strong dissatisfaction with having to remain on such therapy for the rest of their lives.

The Watchman-trial results “were quite compelling, and the device fills a large, unmet need for patients who are inappropriately treated or undertreated” with anticoagulation, said Dr. J. Peter Weiss, an electrophysiologist at the Intermountain Heart Institute in Salt Lake City. “The data show it’s as good as warfarin for preventing ischemic stroke, and the 5-year outcome data [from the PREVENT AF trial] showed a survival advantage largely based on a reduced rate of hemorrhagic stroke” compared with patients on warfarin. “The benefit from Watchman is not just in preventing ischemic strokes,” Dr. Weiss said in an interview.

Researchers presented the 5-year outcomes from PROTECT AF to the FDA in October 2014, and while those results remain unpublished, Dr. Shephal K. Doshi, director of cardiac electrophysiology at Saint Johns Health Center in Santa Monica, Calif., presented them at the Heart Rhythm Society annual meeting in Boston in May. The 5-year outcomes showed that compared with patients treated chronically with warfarin, those who had received a Watchman device had a 39% relative risk reduction for the study’s primary, combined endpoint, a 32% relative risk reduction in the incidence of all strokes, and a 56% statistically significant relative risk reduction in cardiovascular deaths plus unexplained deaths. The 4-year follow-up results from PROTECT AF, with a similar mortality advantage for Watchman over warfarin, were published last year (JAMA. 2014 Nov. 19; 312[19]:1988-98).

The patients who could benefit the most from receiving a Watchman device fall into two categories, Dr. Weiss said: AF patients at high risk for both stroke and bleeding, identified by their high scores on both the CHA2DS2-VASc and HAS-BLED formulas, and relatively young AF patients with a high CHA₂DS₂-VASc score who face the prospect of receiving warfarin or another anticoagulant for a long period of time, possibly several decades. An AF patient who is, for example, 66 years old may have a moderate risk for a serious bleeding event of about 0.5%/year on warfarin or a new oral anticoagulant (NOAC) such as apixaban (Eliquis), dabigatran (Pradaxa), edoxaban (Savaysa), or rivaroxaban (Xarelto), but if that patient were to live for 20 years, the cumulative risk for a major bleeding event could be about 10%, he noted.

Dr. Gordon F. Tomaselli, an electrophysiologist, professor of medicine, and chief of cardiology at Johns Hopkins University in Baltimore, envisions a similar target population: “People who cannot or will not take warfarin or a new oral anticoagulant,” he said. He cited AF patients with a CHA₂DS₂-VASc score of at least 2, but perhaps in most cases for serious Watchman consideration with an even higher CHA₂DS₂-VASc score and hence an even greater stroke risk, as well as an inability to received optimal anticoagulant-drug treatment.

“Right now Watchman fills a small but important niche. If a patient is eligible for an oral anticoagulant and not especially averse to taking one I’d go with that, especially if the patient does not closely resemble those enrolled in the trials, because our experience with NOACs is quite good. But once we get good at placing Watchman and our experience grows, you’ll start to see the indications expand,” he predicted.

Mitchel L. Zoler/FrontlineMedical News

Dr. Saibal Kar, director of interventional cardiology research at Cedars-Sinai Medical Center in Los Angeles and a lead collaborator on the Watchman pivotal trials, agreed that for the time being as well as the foreseeable future Watchman remains a “second-line” option for patients who clearly fail the first line of treatment with warfarin or a NOAC (although Dr. Kar still prefers warfarin). “I absolutely start patients on warfarin and see how they do” and then he offers Watchman to patients who “for various reasons cannot take warfarin or a NOAC,” which could mean serious bleeding episodes or a clear pattern of noncompliance, Dr. Kar said in an interview. Some patients also opt for Watchman because of lifestyle issues, such as a history of falls, or patients who engage in potentially bruising sports such as skiing, he said.

Dr. Kar highlighted the evidence that with longer follow-up, Watchman is not only comparable to warfarin for safety and efficacy, the endpoint specified in the pivotal trials, but also showed a strong signal for long-term superiority in the 4- and 5-year results from PROTECT AF. “For a lot of patients who have challenges [with bleeding complications] Watchman is a great option. When you prevent life-threatening bleeds, it translates into a mortality benefit.”

A cautionary view for the current role of Watchman came in a June editorial written by two physicians at Beth Israel Deaconess Hospital in Boston, who warned that in selected patients Watchman “may be safe, effective, and preferable to chronic warfarin thromboembolic prophylaxis in AF, but at this point many questions surrounding its safety and long-term efficacy remain unanswered” (J Am Coll Cardiol. 2015 June 23;65[24]:2624-7). Dr. Jonathan W. Waks and Dr. Warren J. Manning went on to say in their commentary that “at this point in time, it appears that patients treated with Watchman may pay early (procedural complications) and may also possibly pay later (late thromboembolism).”

Mitchel L. Zoler/Frontline Medical News

In a reply to this critique, Dr. David R. Holmes Jr., professor of medicine and an electrophysiologist and interventional cardiologist at the Mayo Clinic in Rochester, Minn., and developer of the Watchman device, countered that while extremely long-term outcomes from Watchman, beyond 5 years, are not yet available, the long-term consequences of extremely prolonged chronic anticoagulation that continues for a similarly extended period also remain undocumented. He noted that hemorrhagic stroke poses the greatest stroke danger to patients maintained on anticoagulant therapy, but the meta-analysis of Watchman results that he and his associates published in June – the article that was the subject for the comment by Dr. Waks and Dr. Manning – showed a 78% relative risk reduction in hemorrhagic strokes among Watchman recipients compared with control AF patients who received warfarin (J Am Coll Cardiol. 2015 June 23;65[24]:2614-23).

Dr. Holmes acknowledged that patients treated with Watchman and no anticoagulant can develop ischemic strokes from causes aside from clot formation in the LAA. But he stressed that the meta-analysis he published in June showed a striking 52% relative decrease in cardiovascular or unexplained deaths during and average 2.7 years of follow-up compared with the control patients treated with warfarin.

“It is extraordinarily uncommon to have this magnitude of improved survival in a relatively small number of patients,” and the survival benefit was consistent across both randomized Watchman trials as well as in both continued access cohorts that followed each of the two trials, Dr. Holmes said in an interview.

“I fully accept that we don’t have data beyond 5 years, but the data from PROTECT AF out to 5 years showed no evidence of late strokes or other adverse events,” said Dr. Vivek Y. Reddy, professor of medicine and director of the cardiac arrhythmia service at Mount Sinai Hospital in New York. “In fact, the longer you follow these patients [who received Watchman], the more benefit you see, because these patients are not on an oral anticoagulant long term. Concern about long-term outcomes “is not borne out in the data,” said Dr. Reddy, another leader of the team of interventionalists and electrophysiologists who ran the Watchman trials.

Mitchel L. Zoler/FrontlineMedical News

“If a patient with AF comes to me and says ‘I don’t want to take the damn anticoagulants, I want a Watchman,’ and if the patient understands the risks and benefits of Watchman, then I’m 100% fine” facilitating placement of the device in such a patient, explained Dr. Kowey, someone who remains very skeptical of Watchman’s current track record and role. “But what should not happen is for physicians to try to sell Watchman to their patients. Physicians should not tell patients that you don’t need to worry about anticoagulation anymore because I can put in a Watchman and it’s the end of the story. We’re very short of having enough information right now to recommend it to patients” this way. Despite this information shortfall, “I know for a fact” that this sort of promotion of Watchman occurs right now from physicians with an economic incentive to place the device into patients, Dr. Kowey said in an interview.

While some physicians may excessively promote Watchman, they also likely have a receptive audience. “I don’t think it will be hard to find patients who are interested in the device. The challenge will be to figure out if a patient is a good candidate,” said Dr. Paul Varosy, director of electrophysiology at the Denver VA Medical Center. “I have patients and physicians who ask all the time when we will start making the device available. I care for many patients who absolutely despise warfarin and NOACs, and they would love to have a way to get off their medication that does not involve having a risk for a massive stroke,” he said. “What is striking to me is how many patients are interested in this device without being aware of what they would be getting.”

Paying for Watchman

Economic incentives for placing Watchman into patients aside, paying for the device right now and for the procedure that’s involved is no easy matter. Several cardiologists active in Watchman programs scattered around the United States report substantial problems encountered since March with health insurance coverage for the device and placement procedure, and they add that uncertainties about coverage or denied coverage has significantly limited the number of patients who have received the device.

One of the more glaring examples is at the Mayo Clinic in Rochester, Minn., the program led by Dr. Holmes, who helped develop the Watchman technology. He and his associates have placed roughly 20 of the devices since March, but in August he said that his program had “about 40-50 patients” who had been fully screened for the device and looked like they were excellent candidates but were refused coverage by their health insurers. And after some of the 20 patients had already received a Watchman at Mayo, their insurers denied payment, cases that now are on appeal, Dr. Holmes said.

Other active programs report similar difficulties. Dr. Reddy said his program had placed Watchman into about 30-35 patients through the end of August, and while “a majority” of his candidate patients received authorization from their health insurers, others have not received authorization and are on appeal. Insurance coverage is “clearly a problem,” he said in an interview.

Dr. Kar said his Cedars-Sinai program in Los Angles has put Watchman into about 55 patients since last March, and the pace recently accelerated with his treating 13 patients during a 2-day period in August, but he has also seen “lots of problems with insurance,” with appeals usually needed on a case-by-case basis. “We’ve had several appropriate patients who have not received the device because they were not covered,” although most of those cases remain on appeal.

At the University of Kansas in Kansas City, “reimbursement issues have been a major hindrance to widespread use of the device,” and has so far limited placement to just a few patients, said Dr. Dhanunjaya R. Lakkireddy, professor of medicine and director of the University’s Center for Excellence in AF and Complex Arrhythmias. At the Intermountain Heart Institute in Salt Lake City, operators have done just 3 placements since the device’s approval, after doing 128 Watchman placements during the trials and continued access programs. One of the patients paid for the device and procedure completely out of pocket, said Dr. Weiss, a bill that Dr. Kar said runs more than $20,000. The second of the Intermountain patients received Medicare coverage, and in the third case “we met with CMS and are waiting to hear,” Dr. Weiss said. “We are being very cautious to do cases that are very well indicated” to help better ensure that they will receive medical insurance coverage, Dr. Weiss said in an interview.

In May, the CMS began a National Coverage Analysis for Watchman prompted by a request from the device’s manufacturer, Boston Scientific. The appeal for Medicare coverage received support in a June letter written by the presidents of the American College of Cardiology, the Heart Rhythm Society, and the Society for Cardiovascular Angiography and Interventions.

A national coverage determination by the CMS in favor of paying for Medicare patients who undergo Watchman placement “would be a huge benefit,” said Dr. Holmes, who predicted that private insurers would then follow the CMS’ lead and cover the procedure as well. The CMS set Nov. 21, 2015, as the deadline for its decision.

Patients with anticoagulant contraindications will take more time

Even if the CMS decides in favor of reimbursing Watchman placement, the request that it received from Boston Scientific specified coverage for the FDA-approved indication, which stipulates placement in patients able to undergo warfarin treatment. That means for patients who are unable to receive anticoagulant treatment, placement constitutes off-label use that will likely remain unreimbursed, yet these are the very patients that experts agree form an obvious target for Watchman intervention. Currently, these AF patients generally rely on chronic aspirin treatment as their only protection against ischemic stroke.

The only formal, reported experience using Watchman in AF patients who did not also receive warfarin during the first 6 weeks following placement came in a 150-patient, uncontrolled feasibility study, ASAP(ASA Plavix Feasibility Study With WATCHMAN Left Atrial Appendage Closure Technology) run at four centers in Europe (J Am Coll Cardiol. 2013 June 25;61[25]:2551-6). All of the enrolled patients were ineligible to receive warfarin, and instead following Watchman placement these patients received either clopidogrel or ticlopidine for 6 months and chronic treatment with aspirin (dual antiplatelet therapy [DAPT]). Follow-up averaged 14 months, and based on the patients’ average CHA₂DS₂-VASc score at entry the expected annualized rate of ischemic stroke in these patients was roughly 7%.

However, their observed rate was just 1.7%, and their rate of periprocedural and postprocedural complications roughly matched the rates seen in the first Watchman randomized trial. The researchers who ran the study concluded that the results showed that “Watchman can be safely implanted without a warfarin transition.”

Although the ASAP results showed “Watchman is very effective for stroke prevention” without early anticoagulation following placement, “I’m not sure how one could use Watchman for patients contraindicated for oral anticoagulation,” said Dr. Lakkireddy. “This is a controversial area, and one has to be cautious about cavalier off-label use of the device.”

“I think we need to know more about the [ASAP] data before we’d feel comfortable offering the Watchman device” to patients contraindicated for oral anticoagulation, said Dr. Weiss.

Patients with a total contraindication against treatment with warfarin or a NOAC have the greatest need, said Dr. Reddy. “The problem is, we don’t have much safety data” for these patients, and while the results from the ASAP trial showed the device can be safely placed just using DAPT, the numbers were small and the device is not approved” for use in this setting, said Dr. Reddy, the lead investigator for the ASAP study.

The solution to the dilemma posed by this patient group may lie in the ASAP 2 study, a large, multicenter trial that will enroll AF patients with a contraindication to oral anticoagulation and will compare Watchman placement followed by several months of antiplatelet treatment with DAPT head-to-head with patients randomized to today’s standard treatment of aspirin only. The trial will be sponsored by Boston Scientific, and should start by the end of this year, Dr. Reddy said. He envisions enrolling many of the AF patients he sees with an absolute contraindication to oral anticoagulant treatment in the trial once it starts, though it will mean that only half the enrolled patients will receive a Watchman device.

Dr. Holmes sees registry data as another possible route for eventually expanding the labeled indication for Watchman to patients who can’t receive warfarin or another anticoagulant. He cited the precedent of the FDA broadening the labeled indication for transcatheter aortic-valve replacement in 2013 based in part on U.S. registry data as well as on data collected in Europe.

One potential source of U.S. patients who could wind up receiving only brief warfarin treatment after Watchman placement would be those who develop a major bleed soon after starting on anticoagulation, an event that would prompt most physicians to discontinue and not restart warfarin, Dr. Holmes said. He suggested that in these circumstances patients receive DAPT for 6 months using aspirin and clopidogrel, following the protocol tested in ASAP.

The likely source of registry data would be the database that will be created and maintained by the ACC according to an announcement from the ACC in August. This registry is seen by the ACC as addressing the need for a postapproval safety and efficacy assessment of 1,000 U.S. Watchman recipients that the FDA mandated as part of its device approval last March.

“The registry will function as the postapproval study mandated by the FDA,” said Dr. Varosy of Denver, who led the effort to develop and structure the ACC’s Watchman registry. One goal of the registry “will be to get a better understanding of how the device performs” in patients who can’t take an anticoagulant. “I think that’s where the strongest rationale is for having a device like this,” he said. “It would be great to do something for patients who can’t take warfarin, but until we have data for that group we’ll just have to wait.”

Recommendations detail appropriate Watchman rollout

A recent review of LAA occlusion-device options by the ACC, Heart Rhythm Society, and Society for Cardiovascular Angiography and Interventions was an attempt by these three U.S. professional societies with a stake in AF management and LAA closure to “address issues critical to the appropriate integration of new technologies into the care of patients with AF” (J Am Coll Cardiol. 2015. doi:10.1016/j.jacc.2015.06.028]). One of the review’s most notable features is a section that makes specific recommendations about the composition of the physician team that assesses prospective AF patients for LAA closure and performs the procedure. The document suggests the process involve a team of physicians with expertise in electrophysiology, cardiac catheterization, stroke prevention, echocardiography, x-ray imaging, and possibly anesthesiology if general anesthesia is planned. The panel also recommended having a cardiac surgeon on hand for surgical backup if needed. The review also made recommendations on the facilities needed to safely and effectively perform LAA occlusion, the training that should be in place for the operator who performs the procedure, the protocols that should exist to guide patient management before, during, and after occlusion, the methods used to select AF patients for LAA occlusion, and the need for a U.S.-based LAA registry.

Despite these recommendations, “it is currently too early to tell how Watchman will be introduced into practice with respect to facilities, training, etc.,” Dr. Frederick A. Masoudi, a cardiologist at the University of Colorado in Denver and chair of the review committee, said in an interview. The three professional societies “are separately releasing a statement that focuses in greater detail on recommended operator characteristics and training.” This statement is still pending, he said.

A spokeswoman for Boston Scientific said that the company “supports the recommendations [from Dr. Masoudi’s committee], which are very much in line with our established criteria for new implanting centers. We are committed to the rational dispersion of the technology through a disciplined and highly selective approach to center identification. We will ensure that all implanters and implanting centers meet specific prerequisites including appropriate facilities and a dedicated and experienced team to perform the procedure. In addition, we will require implanters and echocardiographers to complete a rigorous clinical training program.”

As of late August, Boston Scientific identified on its website 32 U.S. centers performing LAA closure using Watchman. The company anticipates that about 100 U.S. centers will be performing the procedure by the end of 2015.

The PREVENT AF and PREVAIL pivotal trials for Watchman and their subsequent continued-access programs were sponsored by Boston Scientific. Dr. Kowey has been a speaker for Boston Scientific and has consulted for several drug companies that market anticoagulants. Dr. Weiss has been a speaker for Boston Scientific and also for St. Jude, Biosense Webster, and Stereotaxis. Dr. Kar has received research grants from Boston Scientific and served as principal investigator for the two continued-access programs that followed the two Watchman pivotal trials. He has also received research grants from Abbott Vascular and St. Jude, and has an equity interest in Coherex. Dr. Holmes and the Mayo Clinic have a financial interest in technology related to Watchman and this technology was licensed to Boston Scientific. Dr. Reddy has been an adviser to and received research grants from Atritech/Boston Scientific. Dr. Lakkireddy, Dr. Varosy, Dr. Masoudi, and Dr. Tomaselli had no disclosures.

[email protected]

On Twitter@mitchelzoler

The Watchman device, approved for routine use by the Food and Drug Administration in March, gives U.S. atrial fibrillation patients their first alternative to chronic anticoagulant treatment for preventing ischemic stroke.

By closing off the sac-like left-atrial appendage (LAA) with Watchman – a plug-like device placed via percutaneous, transcatheter delivery – blood clots cannot form in the LAA, thereby eliminating the source for most of the thrombi that threaten to cause ischemic strokes in patients with atrial fibrillation (AF).

But while many cardiologists welcome this new option that, for the first time, gives AF patients a way to avoid years or even decades of daily treatment with an anticoagulant, U.S. rollout of the device out has not been seamless. In many regions, health insurers have been unwilling to cover payment for Watchman and its placement, say physicians. Medicare AF patients in particular have been in a state of limbo for receiving a Watchman device while the Centers for Medicare and Medicaid Services (CMS) makes a national coverage determination, a decision not expected until later this year.

In addition, the AF patients who arguably are the best candidates for receiving this device are technically ineligible based on Watchman’s labeling as well as a very limited evidence base. The FDA approved the device specifically for patients judged “suitable for warfarin,” a decision driven largely by the two Watchman trials that led to approval. Each of these trials randomized warfarin-eligible patients either to receive the device along with a 6-week course of warfarin following placement to ensure against acute thromboembolic complications, or to chronic warfarin treatment with no device.

Although this design allowed head-to-head comparison between Watchman and the traditional standard for anticoagulation in AF patients, it left unaddressed the question of how Watchman performs in the AF patient population with the most obvious indication for a mechanical solution to stroke risk: patients who are completely intolerant of anticoagulation treatment. By strict labeling criteria those patients, desperate for an effective means to reduce their stroke risk, are ineligible to receive Watchman.

“It’s approved for patients who can take warfarin, and that’s wrong,” said Dr. Peter R. Kowey, an AF specialist and professor and director of the Center for Clinical Cardiology at the Lankenau Institute for Medical Research in Wynnewood, Pa. “Most of us in clinical practice believe Watchman has the potential to help patients who would be difficult to anticoagulate long term. This is how it’s used around the world.”

Who should get Watchman right now?

With patients with contraindications for anticoagulants excluded by current labeling, who are the right patients to get this device, especially with long-term experience still relatively limited? Many AF experts say they currently see targeting it to AF patients who are clearly at high risk from both stroke and anticoagulation, as well as possibly also patients who face less of a risk from an anticoagulant treatment but express a strong dissatisfaction with having to remain on such therapy for the rest of their lives.

The Watchman-trial results “were quite compelling, and the device fills a large, unmet need for patients who are inappropriately treated or undertreated” with anticoagulation, said Dr. J. Peter Weiss, an electrophysiologist at the Intermountain Heart Institute in Salt Lake City. “The data show it’s as good as warfarin for preventing ischemic stroke, and the 5-year outcome data [from the PREVENT AF trial] showed a survival advantage largely based on a reduced rate of hemorrhagic stroke” compared with patients on warfarin. “The benefit from Watchman is not just in preventing ischemic strokes,” Dr. Weiss said in an interview.

Researchers presented the 5-year outcomes from PROTECT AF to the FDA in October 2014, and while those results remain unpublished, Dr. Shephal K. Doshi, director of cardiac electrophysiology at Saint Johns Health Center in Santa Monica, Calif., presented them at the Heart Rhythm Society annual meeting in Boston in May. The 5-year outcomes showed that compared with patients treated chronically with warfarin, those who had received a Watchman device had a 39% relative risk reduction for the study’s primary, combined endpoint, a 32% relative risk reduction in the incidence of all strokes, and a 56% statistically significant relative risk reduction in cardiovascular deaths plus unexplained deaths. The 4-year follow-up results from PROTECT AF, with a similar mortality advantage for Watchman over warfarin, were published last year (JAMA. 2014 Nov. 19; 312[19]:1988-98).

The patients who could benefit the most from receiving a Watchman device fall into two categories, Dr. Weiss said: AF patients at high risk for both stroke and bleeding, identified by their high scores on both the CHA2DS2-VASc and HAS-BLED formulas, and relatively young AF patients with a high CHA₂DS₂-VASc score who face the prospect of receiving warfarin or another anticoagulant for a long period of time, possibly several decades. An AF patient who is, for example, 66 years old may have a moderate risk for a serious bleeding event of about 0.5%/year on warfarin or a new oral anticoagulant (NOAC) such as apixaban (Eliquis), dabigatran (Pradaxa), edoxaban (Savaysa), or rivaroxaban (Xarelto), but if that patient were to live for 20 years, the cumulative risk for a major bleeding event could be about 10%, he noted.

Dr. Gordon F. Tomaselli, an electrophysiologist, professor of medicine, and chief of cardiology at Johns Hopkins University in Baltimore, envisions a similar target population: “People who cannot or will not take warfarin or a new oral anticoagulant,” he said. He cited AF patients with a CHA₂DS₂-VASc score of at least 2, but perhaps in most cases for serious Watchman consideration with an even higher CHA₂DS₂-VASc score and hence an even greater stroke risk, as well as an inability to received optimal anticoagulant-drug treatment.

“Right now Watchman fills a small but important niche. If a patient is eligible for an oral anticoagulant and not especially averse to taking one I’d go with that, especially if the patient does not closely resemble those enrolled in the trials, because our experience with NOACs is quite good. But once we get good at placing Watchman and our experience grows, you’ll start to see the indications expand,” he predicted.

Mitchel L. Zoler/FrontlineMedical News

Dr. Saibal Kar, director of interventional cardiology research at Cedars-Sinai Medical Center in Los Angeles and a lead collaborator on the Watchman pivotal trials, agreed that for the time being as well as the foreseeable future Watchman remains a “second-line” option for patients who clearly fail the first line of treatment with warfarin or a NOAC (although Dr. Kar still prefers warfarin). “I absolutely start patients on warfarin and see how they do” and then he offers Watchman to patients who “for various reasons cannot take warfarin or a NOAC,” which could mean serious bleeding episodes or a clear pattern of noncompliance, Dr. Kar said in an interview. Some patients also opt for Watchman because of lifestyle issues, such as a history of falls, or patients who engage in potentially bruising sports such as skiing, he said.

Dr. Kar highlighted the evidence that with longer follow-up, Watchman is not only comparable to warfarin for safety and efficacy, the endpoint specified in the pivotal trials, but also showed a strong signal for long-term superiority in the 4- and 5-year results from PROTECT AF. “For a lot of patients who have challenges [with bleeding complications] Watchman is a great option. When you prevent life-threatening bleeds, it translates into a mortality benefit.”

A cautionary view for the current role of Watchman came in a June editorial written by two physicians at Beth Israel Deaconess Hospital in Boston, who warned that in selected patients Watchman “may be safe, effective, and preferable to chronic warfarin thromboembolic prophylaxis in AF, but at this point many questions surrounding its safety and long-term efficacy remain unanswered” (J Am Coll Cardiol. 2015 June 23;65[24]:2624-7). Dr. Jonathan W. Waks and Dr. Warren J. Manning went on to say in their commentary that “at this point in time, it appears that patients treated with Watchman may pay early (procedural complications) and may also possibly pay later (late thromboembolism).”

Mitchel L. Zoler/Frontline Medical News

In a reply to this critique, Dr. David R. Holmes Jr., professor of medicine and an electrophysiologist and interventional cardiologist at the Mayo Clinic in Rochester, Minn., and developer of the Watchman device, countered that while extremely long-term outcomes from Watchman, beyond 5 years, are not yet available, the long-term consequences of extremely prolonged chronic anticoagulation that continues for a similarly extended period also remain undocumented. He noted that hemorrhagic stroke poses the greatest stroke danger to patients maintained on anticoagulant therapy, but the meta-analysis of Watchman results that he and his associates published in June – the article that was the subject for the comment by Dr. Waks and Dr. Manning – showed a 78% relative risk reduction in hemorrhagic strokes among Watchman recipients compared with control AF patients who received warfarin (J Am Coll Cardiol. 2015 June 23;65[24]:2614-23).

Dr. Holmes acknowledged that patients treated with Watchman and no anticoagulant can develop ischemic strokes from causes aside from clot formation in the LAA. But he stressed that the meta-analysis he published in June showed a striking 52% relative decrease in cardiovascular or unexplained deaths during and average 2.7 years of follow-up compared with the control patients treated with warfarin.

“It is extraordinarily uncommon to have this magnitude of improved survival in a relatively small number of patients,” and the survival benefit was consistent across both randomized Watchman trials as well as in both continued access cohorts that followed each of the two trials, Dr. Holmes said in an interview.

“I fully accept that we don’t have data beyond 5 years, but the data from PROTECT AF out to 5 years showed no evidence of late strokes or other adverse events,” said Dr. Vivek Y. Reddy, professor of medicine and director of the cardiac arrhythmia service at Mount Sinai Hospital in New York. “In fact, the longer you follow these patients [who received Watchman], the more benefit you see, because these patients are not on an oral anticoagulant long term. Concern about long-term outcomes “is not borne out in the data,” said Dr. Reddy, another leader of the team of interventionalists and electrophysiologists who ran the Watchman trials.

Mitchel L. Zoler/FrontlineMedical News

“If a patient with AF comes to me and says ‘I don’t want to take the damn anticoagulants, I want a Watchman,’ and if the patient understands the risks and benefits of Watchman, then I’m 100% fine” facilitating placement of the device in such a patient, explained Dr. Kowey, someone who remains very skeptical of Watchman’s current track record and role. “But what should not happen is for physicians to try to sell Watchman to their patients. Physicians should not tell patients that you don’t need to worry about anticoagulation anymore because I can put in a Watchman and it’s the end of the story. We’re very short of having enough information right now to recommend it to patients” this way. Despite this information shortfall, “I know for a fact” that this sort of promotion of Watchman occurs right now from physicians with an economic incentive to place the device into patients, Dr. Kowey said in an interview.

While some physicians may excessively promote Watchman, they also likely have a receptive audience. “I don’t think it will be hard to find patients who are interested in the device. The challenge will be to figure out if a patient is a good candidate,” said Dr. Paul Varosy, director of electrophysiology at the Denver VA Medical Center. “I have patients and physicians who ask all the time when we will start making the device available. I care for many patients who absolutely despise warfarin and NOACs, and they would love to have a way to get off their medication that does not involve having a risk for a massive stroke,” he said. “What is striking to me is how many patients are interested in this device without being aware of what they would be getting.”

Paying for Watchman

Economic incentives for placing Watchman into patients aside, paying for the device right now and for the procedure that’s involved is no easy matter. Several cardiologists active in Watchman programs scattered around the United States report substantial problems encountered since March with health insurance coverage for the device and placement procedure, and they add that uncertainties about coverage or denied coverage has significantly limited the number of patients who have received the device.

One of the more glaring examples is at the Mayo Clinic in Rochester, Minn., the program led by Dr. Holmes, who helped develop the Watchman technology. He and his associates have placed roughly 20 of the devices since March, but in August he said that his program had “about 40-50 patients” who had been fully screened for the device and looked like they were excellent candidates but were refused coverage by their health insurers. And after some of the 20 patients had already received a Watchman at Mayo, their insurers denied payment, cases that now are on appeal, Dr. Holmes said.

Other active programs report similar difficulties. Dr. Reddy said his program had placed Watchman into about 30-35 patients through the end of August, and while “a majority” of his candidate patients received authorization from their health insurers, others have not received authorization and are on appeal. Insurance coverage is “clearly a problem,” he said in an interview.

Dr. Kar said his Cedars-Sinai program in Los Angles has put Watchman into about 55 patients since last March, and the pace recently accelerated with his treating 13 patients during a 2-day period in August, but he has also seen “lots of problems with insurance,” with appeals usually needed on a case-by-case basis. “We’ve had several appropriate patients who have not received the device because they were not covered,” although most of those cases remain on appeal.

At the University of Kansas in Kansas City, “reimbursement issues have been a major hindrance to widespread use of the device,” and has so far limited placement to just a few patients, said Dr. Dhanunjaya R. Lakkireddy, professor of medicine and director of the University’s Center for Excellence in AF and Complex Arrhythmias. At the Intermountain Heart Institute in Salt Lake City, operators have done just 3 placements since the device’s approval, after doing 128 Watchman placements during the trials and continued access programs. One of the patients paid for the device and procedure completely out of pocket, said Dr. Weiss, a bill that Dr. Kar said runs more than $20,000. The second of the Intermountain patients received Medicare coverage, and in the third case “we met with CMS and are waiting to hear,” Dr. Weiss said. “We are being very cautious to do cases that are very well indicated” to help better ensure that they will receive medical insurance coverage, Dr. Weiss said in an interview.

In May, the CMS began a National Coverage Analysis for Watchman prompted by a request from the device’s manufacturer, Boston Scientific. The appeal for Medicare coverage received support in a June letter written by the presidents of the American College of Cardiology, the Heart Rhythm Society, and the Society for Cardiovascular Angiography and Interventions.

A national coverage determination by the CMS in favor of paying for Medicare patients who undergo Watchman placement “would be a huge benefit,” said Dr. Holmes, who predicted that private insurers would then follow the CMS’ lead and cover the procedure as well. The CMS set Nov. 21, 2015, as the deadline for its decision.

Patients with anticoagulant contraindications will take more time

Even if the CMS decides in favor of reimbursing Watchman placement, the request that it received from Boston Scientific specified coverage for the FDA-approved indication, which stipulates placement in patients able to undergo warfarin treatment. That means for patients who are unable to receive anticoagulant treatment, placement constitutes off-label use that will likely remain unreimbursed, yet these are the very patients that experts agree form an obvious target for Watchman intervention. Currently, these AF patients generally rely on chronic aspirin treatment as their only protection against ischemic stroke.

The only formal, reported experience using Watchman in AF patients who did not also receive warfarin during the first 6 weeks following placement came in a 150-patient, uncontrolled feasibility study, ASAP(ASA Plavix Feasibility Study With WATCHMAN Left Atrial Appendage Closure Technology) run at four centers in Europe (J Am Coll Cardiol. 2013 June 25;61[25]:2551-6). All of the enrolled patients were ineligible to receive warfarin, and instead following Watchman placement these patients received either clopidogrel or ticlopidine for 6 months and chronic treatment with aspirin (dual antiplatelet therapy [DAPT]). Follow-up averaged 14 months, and based on the patients’ average CHA₂DS₂-VASc score at entry the expected annualized rate of ischemic stroke in these patients was roughly 7%.

However, their observed rate was just 1.7%, and their rate of periprocedural and postprocedural complications roughly matched the rates seen in the first Watchman randomized trial. The researchers who ran the study concluded that the results showed that “Watchman can be safely implanted without a warfarin transition.”

Although the ASAP results showed “Watchman is very effective for stroke prevention” without early anticoagulation following placement, “I’m not sure how one could use Watchman for patients contraindicated for oral anticoagulation,” said Dr. Lakkireddy. “This is a controversial area, and one has to be cautious about cavalier off-label use of the device.”

“I think we need to know more about the [ASAP] data before we’d feel comfortable offering the Watchman device” to patients contraindicated for oral anticoagulation, said Dr. Weiss.

Patients with a total contraindication against treatment with warfarin or a NOAC have the greatest need, said Dr. Reddy. “The problem is, we don’t have much safety data” for these patients, and while the results from the ASAP trial showed the device can be safely placed just using DAPT, the numbers were small and the device is not approved” for use in this setting, said Dr. Reddy, the lead investigator for the ASAP study.

The solution to the dilemma posed by this patient group may lie in the ASAP 2 study, a large, multicenter trial that will enroll AF patients with a contraindication to oral anticoagulation and will compare Watchman placement followed by several months of antiplatelet treatment with DAPT head-to-head with patients randomized to today’s standard treatment of aspirin only. The trial will be sponsored by Boston Scientific, and should start by the end of this year, Dr. Reddy said. He envisions enrolling many of the AF patients he sees with an absolute contraindication to oral anticoagulant treatment in the trial once it starts, though it will mean that only half the enrolled patients will receive a Watchman device.

Dr. Holmes sees registry data as another possible route for eventually expanding the labeled indication for Watchman to patients who can’t receive warfarin or another anticoagulant. He cited the precedent of the FDA broadening the labeled indication for transcatheter aortic-valve replacement in 2013 based in part on U.S. registry data as well as on data collected in Europe.

One potential source of U.S. patients who could wind up receiving only brief warfarin treatment after Watchman placement would be those who develop a major bleed soon after starting on anticoagulation, an event that would prompt most physicians to discontinue and not restart warfarin, Dr. Holmes said. He suggested that in these circumstances patients receive DAPT for 6 months using aspirin and clopidogrel, following the protocol tested in ASAP.

The likely source of registry data would be the database that will be created and maintained by the ACC according to an announcement from the ACC in August. This registry is seen by the ACC as addressing the need for a postapproval safety and efficacy assessment of 1,000 U.S. Watchman recipients that the FDA mandated as part of its device approval last March.

“The registry will function as the postapproval study mandated by the FDA,” said Dr. Varosy of Denver, who led the effort to develop and structure the ACC’s Watchman registry. One goal of the registry “will be to get a better understanding of how the device performs” in patients who can’t take an anticoagulant. “I think that’s where the strongest rationale is for having a device like this,” he said. “It would be great to do something for patients who can’t take warfarin, but until we have data for that group we’ll just have to wait.”

Recommendations detail appropriate Watchman rollout

A recent review of LAA occlusion-device options by the ACC, Heart Rhythm Society, and Society for Cardiovascular Angiography and Interventions was an attempt by these three U.S. professional societies with a stake in AF management and LAA closure to “address issues critical to the appropriate integration of new technologies into the care of patients with AF” (J Am Coll Cardiol. 2015. doi:10.1016/j.jacc.2015.06.028]). One of the review’s most notable features is a section that makes specific recommendations about the composition of the physician team that assesses prospective AF patients for LAA closure and performs the procedure. The document suggests the process involve a team of physicians with expertise in electrophysiology, cardiac catheterization, stroke prevention, echocardiography, x-ray imaging, and possibly anesthesiology if general anesthesia is planned. The panel also recommended having a cardiac surgeon on hand for surgical backup if needed. The review also made recommendations on the facilities needed to safely and effectively perform LAA occlusion, the training that should be in place for the operator who performs the procedure, the protocols that should exist to guide patient management before, during, and after occlusion, the methods used to select AF patients for LAA occlusion, and the need for a U.S.-based LAA registry.

Despite these recommendations, “it is currently too early to tell how Watchman will be introduced into practice with respect to facilities, training, etc.,” Dr. Frederick A. Masoudi, a cardiologist at the University of Colorado in Denver and chair of the review committee, said in an interview. The three professional societies “are separately releasing a statement that focuses in greater detail on recommended operator characteristics and training.” This statement is still pending, he said.

A spokeswoman for Boston Scientific said that the company “supports the recommendations [from Dr. Masoudi’s committee], which are very much in line with our established criteria for new implanting centers. We are committed to the rational dispersion of the technology through a disciplined and highly selective approach to center identification. We will ensure that all implanters and implanting centers meet specific prerequisites including appropriate facilities and a dedicated and experienced team to perform the procedure. In addition, we will require implanters and echocardiographers to complete a rigorous clinical training program.”

As of late August, Boston Scientific identified on its website 32 U.S. centers performing LAA closure using Watchman. The company anticipates that about 100 U.S. centers will be performing the procedure by the end of 2015.

The PREVENT AF and PREVAIL pivotal trials for Watchman and their subsequent continued-access programs were sponsored by Boston Scientific. Dr. Kowey has been a speaker for Boston Scientific and has consulted for several drug companies that market anticoagulants. Dr. Weiss has been a speaker for Boston Scientific and also for St. Jude, Biosense Webster, and Stereotaxis. Dr. Kar has received research grants from Boston Scientific and served as principal investigator for the two continued-access programs that followed the two Watchman pivotal trials. He has also received research grants from Abbott Vascular and St. Jude, and has an equity interest in Coherex. Dr. Holmes and the Mayo Clinic have a financial interest in technology related to Watchman and this technology was licensed to Boston Scientific. Dr. Reddy has been an adviser to and received research grants from Atritech/Boston Scientific. Dr. Lakkireddy, Dr. Varosy, Dr. Masoudi, and Dr. Tomaselli had no disclosures.

[email protected]

On Twitter@mitchelzoler

The Watchman device, approved for routine use by the Food and Drug Administration in March, gives U.S. atrial fibrillation patients their first alternative to chronic anticoagulant treatment for preventing ischemic stroke.

By closing off the sac-like left-atrial appendage (LAA) with Watchman – a plug-like device placed via percutaneous, transcatheter delivery – blood clots cannot form in the LAA, thereby eliminating the source for most of the thrombi that threaten to cause ischemic strokes in patients with atrial fibrillation (AF).

But while many cardiologists welcome this new option that, for the first time, gives AF patients a way to avoid years or even decades of daily treatment with an anticoagulant, U.S. rollout of the device out has not been seamless. In many regions, health insurers have been unwilling to cover payment for Watchman and its placement, say physicians. Medicare AF patients in particular have been in a state of limbo for receiving a Watchman device while the Centers for Medicare and Medicaid Services (CMS) makes a national coverage determination, a decision not expected until later this year.

In addition, the AF patients who arguably are the best candidates for receiving this device are technically ineligible based on Watchman’s labeling as well as a very limited evidence base. The FDA approved the device specifically for patients judged “suitable for warfarin,” a decision driven largely by the two Watchman trials that led to approval. Each of these trials randomized warfarin-eligible patients either to receive the device along with a 6-week course of warfarin following placement to ensure against acute thromboembolic complications, or to chronic warfarin treatment with no device.

Although this design allowed head-to-head comparison between Watchman and the traditional standard for anticoagulation in AF patients, it left unaddressed the question of how Watchman performs in the AF patient population with the most obvious indication for a mechanical solution to stroke risk: patients who are completely intolerant of anticoagulation treatment. By strict labeling criteria those patients, desperate for an effective means to reduce their stroke risk, are ineligible to receive Watchman.

“It’s approved for patients who can take warfarin, and that’s wrong,” said Dr. Peter R. Kowey, an AF specialist and professor and director of the Center for Clinical Cardiology at the Lankenau Institute for Medical Research in Wynnewood, Pa. “Most of us in clinical practice believe Watchman has the potential to help patients who would be difficult to anticoagulate long term. This is how it’s used around the world.”

Who should get Watchman right now?

With patients with contraindications for anticoagulants excluded by current labeling, who are the right patients to get this device, especially with long-term experience still relatively limited? Many AF experts say they currently see targeting it to AF patients who are clearly at high risk from both stroke and anticoagulation, as well as possibly also patients who face less of a risk from an anticoagulant treatment but express a strong dissatisfaction with having to remain on such therapy for the rest of their lives.

The Watchman-trial results “were quite compelling, and the device fills a large, unmet need for patients who are inappropriately treated or undertreated” with anticoagulation, said Dr. J. Peter Weiss, an electrophysiologist at the Intermountain Heart Institute in Salt Lake City. “The data show it’s as good as warfarin for preventing ischemic stroke, and the 5-year outcome data [from the PREVENT AF trial] showed a survival advantage largely based on a reduced rate of hemorrhagic stroke” compared with patients on warfarin. “The benefit from Watchman is not just in preventing ischemic strokes,” Dr. Weiss said in an interview.

Researchers presented the 5-year outcomes from PROTECT AF to the FDA in October 2014, and while those results remain unpublished, Dr. Shephal K. Doshi, director of cardiac electrophysiology at Saint Johns Health Center in Santa Monica, Calif., presented them at the Heart Rhythm Society annual meeting in Boston in May. The 5-year outcomes showed that compared with patients treated chronically with warfarin, those who had received a Watchman device had a 39% relative risk reduction for the study’s primary, combined endpoint, a 32% relative risk reduction in the incidence of all strokes, and a 56% statistically significant relative risk reduction in cardiovascular deaths plus unexplained deaths. The 4-year follow-up results from PROTECT AF, with a similar mortality advantage for Watchman over warfarin, were published last year (JAMA. 2014 Nov. 19; 312[19]:1988-98).

The patients who could benefit the most from receiving a Watchman device fall into two categories, Dr. Weiss said: AF patients at high risk for both stroke and bleeding, identified by their high scores on both the CHA2DS2-VASc and HAS-BLED formulas, and relatively young AF patients with a high CHA₂DS₂-VASc score who face the prospect of receiving warfarin or another anticoagulant for a long period of time, possibly several decades. An AF patient who is, for example, 66 years old may have a moderate risk for a serious bleeding event of about 0.5%/year on warfarin or a new oral anticoagulant (NOAC) such as apixaban (Eliquis), dabigatran (Pradaxa), edoxaban (Savaysa), or rivaroxaban (Xarelto), but if that patient were to live for 20 years, the cumulative risk for a major bleeding event could be about 10%, he noted.

Dr. Gordon F. Tomaselli, an electrophysiologist, professor of medicine, and chief of cardiology at Johns Hopkins University in Baltimore, envisions a similar target population: “People who cannot or will not take warfarin or a new oral anticoagulant,” he said. He cited AF patients with a CHA₂DS₂-VASc score of at least 2, but perhaps in most cases for serious Watchman consideration with an even higher CHA₂DS₂-VASc score and hence an even greater stroke risk, as well as an inability to received optimal anticoagulant-drug treatment.

“Right now Watchman fills a small but important niche. If a patient is eligible for an oral anticoagulant and not especially averse to taking one I’d go with that, especially if the patient does not closely resemble those enrolled in the trials, because our experience with NOACs is quite good. But once we get good at placing Watchman and our experience grows, you’ll start to see the indications expand,” he predicted.

Mitchel L. Zoler/FrontlineMedical News

Dr. Saibal Kar, director of interventional cardiology research at Cedars-Sinai Medical Center in Los Angeles and a lead collaborator on the Watchman pivotal trials, agreed that for the time being as well as the foreseeable future Watchman remains a “second-line” option for patients who clearly fail the first line of treatment with warfarin or a NOAC (although Dr. Kar still prefers warfarin). “I absolutely start patients on warfarin and see how they do” and then he offers Watchman to patients who “for various reasons cannot take warfarin or a NOAC,” which could mean serious bleeding episodes or a clear pattern of noncompliance, Dr. Kar said in an interview. Some patients also opt for Watchman because of lifestyle issues, such as a history of falls, or patients who engage in potentially bruising sports such as skiing, he said.

Dr. Kar highlighted the evidence that with longer follow-up, Watchman is not only comparable to warfarin for safety and efficacy, the endpoint specified in the pivotal trials, but also showed a strong signal for long-term superiority in the 4- and 5-year results from PROTECT AF. “For a lot of patients who have challenges [with bleeding complications] Watchman is a great option. When you prevent life-threatening bleeds, it translates into a mortality benefit.”

A cautionary view for the current role of Watchman came in a June editorial written by two physicians at Beth Israel Deaconess Hospital in Boston, who warned that in selected patients Watchman “may be safe, effective, and preferable to chronic warfarin thromboembolic prophylaxis in AF, but at this point many questions surrounding its safety and long-term efficacy remain unanswered” (J Am Coll Cardiol. 2015 June 23;65[24]:2624-7). Dr. Jonathan W. Waks and Dr. Warren J. Manning went on to say in their commentary that “at this point in time, it appears that patients treated with Watchman may pay early (procedural complications) and may also possibly pay later (late thromboembolism).”

Mitchel L. Zoler/Frontline Medical News

In a reply to this critique, Dr. David R. Holmes Jr., professor of medicine and an electrophysiologist and interventional cardiologist at the Mayo Clinic in Rochester, Minn., and developer of the Watchman device, countered that while extremely long-term outcomes from Watchman, beyond 5 years, are not yet available, the long-term consequences of extremely prolonged chronic anticoagulation that continues for a similarly extended period also remain undocumented. He noted that hemorrhagic stroke poses the greatest stroke danger to patients maintained on anticoagulant therapy, but the meta-analysis of Watchman results that he and his associates published in June – the article that was the subject for the comment by Dr. Waks and Dr. Manning – showed a 78% relative risk reduction in hemorrhagic strokes among Watchman recipients compared with control AF patients who received warfarin (J Am Coll Cardiol. 2015 June 23;65[24]:2614-23).

Dr. Holmes acknowledged that patients treated with Watchman and no anticoagulant can develop ischemic strokes from causes aside from clot formation in the LAA. But he stressed that the meta-analysis he published in June showed a striking 52% relative decrease in cardiovascular or unexplained deaths during and average 2.7 years of follow-up compared with the control patients treated with warfarin.

“It is extraordinarily uncommon to have this magnitude of improved survival in a relatively small number of patients,” and the survival benefit was consistent across both randomized Watchman trials as well as in both continued access cohorts that followed each of the two trials, Dr. Holmes said in an interview.

“I fully accept that we don’t have data beyond 5 years, but the data from PROTECT AF out to 5 years showed no evidence of late strokes or other adverse events,” said Dr. Vivek Y. Reddy, professor of medicine and director of the cardiac arrhythmia service at Mount Sinai Hospital in New York. “In fact, the longer you follow these patients [who received Watchman], the more benefit you see, because these patients are not on an oral anticoagulant long term. Concern about long-term outcomes “is not borne out in the data,” said Dr. Reddy, another leader of the team of interventionalists and electrophysiologists who ran the Watchman trials.

Mitchel L. Zoler/FrontlineMedical News

“If a patient with AF comes to me and says ‘I don’t want to take the damn anticoagulants, I want a Watchman,’ and if the patient understands the risks and benefits of Watchman, then I’m 100% fine” facilitating placement of the device in such a patient, explained Dr. Kowey, someone who remains very skeptical of Watchman’s current track record and role. “But what should not happen is for physicians to try to sell Watchman to their patients. Physicians should not tell patients that you don’t need to worry about anticoagulation anymore because I can put in a Watchman and it’s the end of the story. We’re very short of having enough information right now to recommend it to patients” this way. Despite this information shortfall, “I know for a fact” that this sort of promotion of Watchman occurs right now from physicians with an economic incentive to place the device into patients, Dr. Kowey said in an interview.

While some physicians may excessively promote Watchman, they also likely have a receptive audience. “I don’t think it will be hard to find patients who are interested in the device. The challenge will be to figure out if a patient is a good candidate,” said Dr. Paul Varosy, director of electrophysiology at the Denver VA Medical Center. “I have patients and physicians who ask all the time when we will start making the device available. I care for many patients who absolutely despise warfarin and NOACs, and they would love to have a way to get off their medication that does not involve having a risk for a massive stroke,” he said. “What is striking to me is how many patients are interested in this device without being aware of what they would be getting.”

Paying for Watchman

Economic incentives for placing Watchman into patients aside, paying for the device right now and for the procedure that’s involved is no easy matter. Several cardiologists active in Watchman programs scattered around the United States report substantial problems encountered since March with health insurance coverage for the device and placement procedure, and they add that uncertainties about coverage or denied coverage has significantly limited the number of patients who have received the device.

One of the more glaring examples is at the Mayo Clinic in Rochester, Minn., the program led by Dr. Holmes, who helped develop the Watchman technology. He and his associates have placed roughly 20 of the devices since March, but in August he said that his program had “about 40-50 patients” who had been fully screened for the device and looked like they were excellent candidates but were refused coverage by their health insurers. And after some of the 20 patients had already received a Watchman at Mayo, their insurers denied payment, cases that now are on appeal, Dr. Holmes said.

Other active programs report similar difficulties. Dr. Reddy said his program had placed Watchman into about 30-35 patients through the end of August, and while “a majority” of his candidate patients received authorization from their health insurers, others have not received authorization and are on appeal. Insurance coverage is “clearly a problem,” he said in an interview.

Dr. Kar said his Cedars-Sinai program in Los Angles has put Watchman into about 55 patients since last March, and the pace recently accelerated with his treating 13 patients during a 2-day period in August, but he has also seen “lots of problems with insurance,” with appeals usually needed on a case-by-case basis. “We’ve had several appropriate patients who have not received the device because they were not covered,” although most of those cases remain on appeal.

At the University of Kansas in Kansas City, “reimbursement issues have been a major hindrance to widespread use of the device,” and has so far limited placement to just a few patients, said Dr. Dhanunjaya R. Lakkireddy, professor of medicine and director of the University’s Center for Excellence in AF and Complex Arrhythmias. At the Intermountain Heart Institute in Salt Lake City, operators have done just 3 placements since the device’s approval, after doing 128 Watchman placements during the trials and continued access programs. One of the patients paid for the device and procedure completely out of pocket, said Dr. Weiss, a bill that Dr. Kar said runs more than $20,000. The second of the Intermountain patients received Medicare coverage, and in the third case “we met with CMS and are waiting to hear,” Dr. Weiss said. “We are being very cautious to do cases that are very well indicated” to help better ensure that they will receive medical insurance coverage, Dr. Weiss said in an interview.

In May, the CMS began a National Coverage Analysis for Watchman prompted by a request from the device’s manufacturer, Boston Scientific. The appeal for Medicare coverage received support in a June letter written by the presidents of the American College of Cardiology, the Heart Rhythm Society, and the Society for Cardiovascular Angiography and Interventions.

A national coverage determination by the CMS in favor of paying for Medicare patients who undergo Watchman placement “would be a huge benefit,” said Dr. Holmes, who predicted that private insurers would then follow the CMS’ lead and cover the procedure as well. The CMS set Nov. 21, 2015, as the deadline for its decision.

Patients with anticoagulant contraindications will take more time

Even if the CMS decides in favor of reimbursing Watchman placement, the request that it received from Boston Scientific specified coverage for the FDA-approved indication, which stipulates placement in patients able to undergo warfarin treatment. That means for patients who are unable to receive anticoagulant treatment, placement constitutes off-label use that will likely remain unreimbursed, yet these are the very patients that experts agree form an obvious target for Watchman intervention. Currently, these AF patients generally rely on chronic aspirin treatment as their only protection against ischemic stroke.

The only formal, reported experience using Watchman in AF patients who did not also receive warfarin during the first 6 weeks following placement came in a 150-patient, uncontrolled feasibility study, ASAP(ASA Plavix Feasibility Study With WATCHMAN Left Atrial Appendage Closure Technology) run at four centers in Europe (J Am Coll Cardiol. 2013 June 25;61[25]:2551-6). All of the enrolled patients were ineligible to receive warfarin, and instead following Watchman placement these patients received either clopidogrel or ticlopidine for 6 months and chronic treatment with aspirin (dual antiplatelet therapy [DAPT]). Follow-up averaged 14 months, and based on the patients’ average CHA₂DS₂-VASc score at entry the expected annualized rate of ischemic stroke in these patients was roughly 7%.

However, their observed rate was just 1.7%, and their rate of periprocedural and postprocedural complications roughly matched the rates seen in the first Watchman randomized trial. The researchers who ran the study concluded that the results showed that “Watchman can be safely implanted without a warfarin transition.”

Although the ASAP results showed “Watchman is very effective for stroke prevention” without early anticoagulation following placement, “I’m not sure how one could use Watchman for patients contraindicated for oral anticoagulation,” said Dr. Lakkireddy. “This is a controversial area, and one has to be cautious about cavalier off-label use of the device.”

“I think we need to know more about the [ASAP] data before we’d feel comfortable offering the Watchman device” to patients contraindicated for oral anticoagulation, said Dr. Weiss.

Patients with a total contraindication against treatment with warfarin or a NOAC have the greatest need, said Dr. Reddy. “The problem is, we don’t have much safety data” for these patients, and while the results from the ASAP trial showed the device can be safely placed just using DAPT, the numbers were small and the device is not approved” for use in this setting, said Dr. Reddy, the lead investigator for the ASAP study.

The solution to the dilemma posed by this patient group may lie in the ASAP 2 study, a large, multicenter trial that will enroll AF patients with a contraindication to oral anticoagulation and will compare Watchman placement followed by several months of antiplatelet treatment with DAPT head-to-head with patients randomized to today’s standard treatment of aspirin only. The trial will be sponsored by Boston Scientific, and should start by the end of this year, Dr. Reddy said. He envisions enrolling many of the AF patients he sees with an absolute contraindication to oral anticoagulant treatment in the trial once it starts, though it will mean that only half the enrolled patients will receive a Watchman device.

Dr. Holmes sees registry data as another possible route for eventually expanding the labeled indication for Watchman to patients who can’t receive warfarin or another anticoagulant. He cited the precedent of the FDA broadening the labeled indication for transcatheter aortic-valve replacement in 2013 based in part on U.S. registry data as well as on data collected in Europe.

One potential source of U.S. patients who could wind up receiving only brief warfarin treatment after Watchman placement would be those who develop a major bleed soon after starting on anticoagulation, an event that would prompt most physicians to discontinue and not restart warfarin, Dr. Holmes said. He suggested that in these circumstances patients receive DAPT for 6 months using aspirin and clopidogrel, following the protocol tested in ASAP.

The likely source of registry data would be the database that will be created and maintained by the ACC according to an announcement from the ACC in August. This registry is seen by the ACC as addressing the need for a postapproval safety and efficacy assessment of 1,000 U.S. Watchman recipients that the FDA mandated as part of its device approval last March.

“The registry will function as the postapproval study mandated by the FDA,” said Dr. Varosy of Denver, who led the effort to develop and structure the ACC’s Watchman registry. One goal of the registry “will be to get a better understanding of how the device performs” in patients who can’t take an anticoagulant. “I think that’s where the strongest rationale is for having a device like this,” he said. “It would be great to do something for patients who can’t take warfarin, but until we have data for that group we’ll just have to wait.”

Recommendations detail appropriate Watchman rollout

A recent review of LAA occlusion-device options by the ACC, Heart Rhythm Society, and Society for Cardiovascular Angiography and Interventions was an attempt by these three U.S. professional societies with a stake in AF management and LAA closure to “address issues critical to the appropriate integration of new technologies into the care of patients with AF” (J Am Coll Cardiol. 2015. doi:10.1016/j.jacc.2015.06.028]). One of the review’s most notable features is a section that makes specific recommendations about the composition of the physician team that assesses prospective AF patients for LAA closure and performs the procedure. The document suggests the process involve a team of physicians with expertise in electrophysiology, cardiac catheterization, stroke prevention, echocardiography, x-ray imaging, and possibly anesthesiology if general anesthesia is planned. The panel also recommended having a cardiac surgeon on hand for surgical backup if needed. The review also made recommendations on the facilities needed to safely and effectively perform LAA occlusion, the training that should be in place for the operator who performs the procedure, the protocols that should exist to guide patient management before, during, and after occlusion, the methods used to select AF patients for LAA occlusion, and the need for a U.S.-based LAA registry.

Despite these recommendations, “it is currently too early to tell how Watchman will be introduced into practice with respect to facilities, training, etc.,” Dr. Frederick A. Masoudi, a cardiologist at the University of Colorado in Denver and chair of the review committee, said in an interview. The three professional societies “are separately releasing a statement that focuses in greater detail on recommended operator characteristics and training.” This statement is still pending, he said.

A spokeswoman for Boston Scientific said that the company “supports the recommendations [from Dr. Masoudi’s committee], which are very much in line with our established criteria for new implanting centers. We are committed to the rational dispersion of the technology through a disciplined and highly selective approach to center identification. We will ensure that all implanters and implanting centers meet specific prerequisites including appropriate facilities and a dedicated and experienced team to perform the procedure. In addition, we will require implanters and echocardiographers to complete a rigorous clinical training program.”

As of late August, Boston Scientific identified on its website 32 U.S. centers performing LAA closure using Watchman. The company anticipates that about 100 U.S. centers will be performing the procedure by the end of 2015.

The PREVENT AF and PREVAIL pivotal trials for Watchman and their subsequent continued-access programs were sponsored by Boston Scientific. Dr. Kowey has been a speaker for Boston Scientific and has consulted for several drug companies that market anticoagulants. Dr. Weiss has been a speaker for Boston Scientific and also for St. Jude, Biosense Webster, and Stereotaxis. Dr. Kar has received research grants from Boston Scientific and served as principal investigator for the two continued-access programs that followed the two Watchman pivotal trials. He has also received research grants from Abbott Vascular and St. Jude, and has an equity interest in Coherex. Dr. Holmes and the Mayo Clinic have a financial interest in technology related to Watchman and this technology was licensed to Boston Scientific. Dr. Reddy has been an adviser to and received research grants from Atritech/Boston Scientific. Dr. Lakkireddy, Dr. Varosy, Dr. Masoudi, and Dr. Tomaselli had no disclosures.

[email protected]

On Twitter@mitchelzoler