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Role grows for heart failure patient-reported outcomes
DALLAS – The Food and Drug Administration is keenly seeking patient-reported outcomes as endpoints in cardiovascular drug or device trials, particularly for heart failure patients, but the bar remains high for getting such an outcome into labeling, said agency officials who regulate cardiovascular disease therapies.
The FDA issued guidance nearly 8 years ago on how to integrate patient-reported outcome (PRO) measures into medical product development, but so far no heart failure drug nor device has met the agency’s standards for documented success in improving a PRO, despite the clear need for these patients to receive patient-centered care, clinicians said.
“We don’t yet have a patient-reported outcome in a label for heart failure,” Paul A. Heidenreich, MD, said during a session on PROs at the annual scientific meeting of the Heart Failure Society of America. He voiced hope that a PRO might end up on the label of a heart failure drug or device sometime in 2018. “Almost half of FDA submissions now include a PRO” as part of the data package, added Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University.
For years, PROs for heart failure weren’t often used in trials, and they remain largely absent from routine practice – an absence Dr. Heidenreich lamented. “Just focusing on mortality in heart failure is really not patient centered,” he said.
Heart failure physicians “are very good at disease-centered care” that focuses on survival and reducing hospitalizations, but “survival is often not as important to patients,” noted Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation program at St. Vincent Medical Group in Indianapolis. She suggested “tailoring treatment to improve patient symptoms, physical function, and quality of life” without necessarily reducing hospital readmissions or increasing survival rates. “Self-reported measures have more meaning for patients,” she said, and called for using PROs to better target interventions to the patients who can most benefit from them.
Two FDA representatives who spoke during the session agreed on the importance of PROs and attested to the agency’s interest in greater reliance on them.
“PROs are a critical complement to the other measures made in device trials,” said Bram Zuckerman, MD, director of the FDA’s division of cardiovascular devices. “We need PRO information because it reflects important aspects of patients’ health-related quality of life.”
The most commonly used PRO measures in device trials today are the Kansas City Cardiomyopathy Questionnaire (J Am Coll Cardiol. 2000 Apr;35[5]:1245-55) and the Minnesota Living With Heart Failure questionnaire, he noted.
“Neither is perfect, but there is a track record in heart failure device development that these two PROs can be helpful.” The FDA’s cardiovascular device division “wants to use PRO information,” Dr. Zuckerman said.
“All-cause mortality is the most unbiased endpoint, but there is interest in PROs,” agreed Ebony Dashiell-Aje, PhD, from the FDA’s office of new drugs in the Center for Drug Evaluation and Research. She highlighted the encouragement that the FDA gave to drug and device developers to include PROs in trials, both in its 2009 guidance document as well as in a “roadmap” from the agency on how to measure PROs in clinical trials. “Unfortunately, in heart failure we struggle to find tools that can adequately measure the patient’s perspective and be sensitive enough to detect a treatment benefit,” she said.
Norman Stockbridge, MD, director of the division of cardiovascular and renal products in the agency’s Office of Drug Evaluation, cited even bigger barriers to FDA approval of PROs as labeled effects from drugs or devices.
Getting a PRO endpoint supported by clinical-trial results that qualify it for an FDA label faces two big challenges. One challenge, he said, is “how much of an effect we need to see in a complex scoring algorithm to know that patients actually received some benefit in a disease that often varies from day to day and from week to week.” The second challenge is that, “in a disease with a high background rate of bad outcomes, you need some evidence that the benefit [from the treatment] is worth any risk,” which is something that can be hard to prove in heart failure when many patients don’t live more than 2 years with the disease, Dr. Stockbridge said in an interview.
“You need to be able to make the argument that the [PRO] benefit is likely perceptible to patients, but that is only half the problem. The other half is whether the developer can rule out that survival is not less than it would have been with no treatment. If patients take this, will they feel better but have a greater risk of being hurt?”
So far, no drug or device developer has succeeded in proving this to the FDA, despite the agency’s 2009 guidance on how it could be done.
That guidance “is one of the two worst and most destructive guidance documents we ever published,” Dr. Stockbridge declared.
Dr. Walsh, Dr. Heidenreich, Dr. Zuckerman, Dr. Dashiell-Aje, and Dr. Stockbridge had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
DALLAS – The Food and Drug Administration is keenly seeking patient-reported outcomes as endpoints in cardiovascular drug or device trials, particularly for heart failure patients, but the bar remains high for getting such an outcome into labeling, said agency officials who regulate cardiovascular disease therapies.
The FDA issued guidance nearly 8 years ago on how to integrate patient-reported outcome (PRO) measures into medical product development, but so far no heart failure drug nor device has met the agency’s standards for documented success in improving a PRO, despite the clear need for these patients to receive patient-centered care, clinicians said.
“We don’t yet have a patient-reported outcome in a label for heart failure,” Paul A. Heidenreich, MD, said during a session on PROs at the annual scientific meeting of the Heart Failure Society of America. He voiced hope that a PRO might end up on the label of a heart failure drug or device sometime in 2018. “Almost half of FDA submissions now include a PRO” as part of the data package, added Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University.
For years, PROs for heart failure weren’t often used in trials, and they remain largely absent from routine practice – an absence Dr. Heidenreich lamented. “Just focusing on mortality in heart failure is really not patient centered,” he said.
Heart failure physicians “are very good at disease-centered care” that focuses on survival and reducing hospitalizations, but “survival is often not as important to patients,” noted Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation program at St. Vincent Medical Group in Indianapolis. She suggested “tailoring treatment to improve patient symptoms, physical function, and quality of life” without necessarily reducing hospital readmissions or increasing survival rates. “Self-reported measures have more meaning for patients,” she said, and called for using PROs to better target interventions to the patients who can most benefit from them.
Two FDA representatives who spoke during the session agreed on the importance of PROs and attested to the agency’s interest in greater reliance on them.
“PROs are a critical complement to the other measures made in device trials,” said Bram Zuckerman, MD, director of the FDA’s division of cardiovascular devices. “We need PRO information because it reflects important aspects of patients’ health-related quality of life.”
The most commonly used PRO measures in device trials today are the Kansas City Cardiomyopathy Questionnaire (J Am Coll Cardiol. 2000 Apr;35[5]:1245-55) and the Minnesota Living With Heart Failure questionnaire, he noted.
“Neither is perfect, but there is a track record in heart failure device development that these two PROs can be helpful.” The FDA’s cardiovascular device division “wants to use PRO information,” Dr. Zuckerman said.
“All-cause mortality is the most unbiased endpoint, but there is interest in PROs,” agreed Ebony Dashiell-Aje, PhD, from the FDA’s office of new drugs in the Center for Drug Evaluation and Research. She highlighted the encouragement that the FDA gave to drug and device developers to include PROs in trials, both in its 2009 guidance document as well as in a “roadmap” from the agency on how to measure PROs in clinical trials. “Unfortunately, in heart failure we struggle to find tools that can adequately measure the patient’s perspective and be sensitive enough to detect a treatment benefit,” she said.
Norman Stockbridge, MD, director of the division of cardiovascular and renal products in the agency’s Office of Drug Evaluation, cited even bigger barriers to FDA approval of PROs as labeled effects from drugs or devices.
Getting a PRO endpoint supported by clinical-trial results that qualify it for an FDA label faces two big challenges. One challenge, he said, is “how much of an effect we need to see in a complex scoring algorithm to know that patients actually received some benefit in a disease that often varies from day to day and from week to week.” The second challenge is that, “in a disease with a high background rate of bad outcomes, you need some evidence that the benefit [from the treatment] is worth any risk,” which is something that can be hard to prove in heart failure when many patients don’t live more than 2 years with the disease, Dr. Stockbridge said in an interview.
“You need to be able to make the argument that the [PRO] benefit is likely perceptible to patients, but that is only half the problem. The other half is whether the developer can rule out that survival is not less than it would have been with no treatment. If patients take this, will they feel better but have a greater risk of being hurt?”
So far, no drug or device developer has succeeded in proving this to the FDA, despite the agency’s 2009 guidance on how it could be done.
That guidance “is one of the two worst and most destructive guidance documents we ever published,” Dr. Stockbridge declared.
Dr. Walsh, Dr. Heidenreich, Dr. Zuckerman, Dr. Dashiell-Aje, and Dr. Stockbridge had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
DALLAS – The Food and Drug Administration is keenly seeking patient-reported outcomes as endpoints in cardiovascular drug or device trials, particularly for heart failure patients, but the bar remains high for getting such an outcome into labeling, said agency officials who regulate cardiovascular disease therapies.
The FDA issued guidance nearly 8 years ago on how to integrate patient-reported outcome (PRO) measures into medical product development, but so far no heart failure drug nor device has met the agency’s standards for documented success in improving a PRO, despite the clear need for these patients to receive patient-centered care, clinicians said.
“We don’t yet have a patient-reported outcome in a label for heart failure,” Paul A. Heidenreich, MD, said during a session on PROs at the annual scientific meeting of the Heart Failure Society of America. He voiced hope that a PRO might end up on the label of a heart failure drug or device sometime in 2018. “Almost half of FDA submissions now include a PRO” as part of the data package, added Dr. Heidenreich, a cardiologist and professor of medicine at Stanford (Calif.) University.
For years, PROs for heart failure weren’t often used in trials, and they remain largely absent from routine practice – an absence Dr. Heidenreich lamented. “Just focusing on mortality in heart failure is really not patient centered,” he said.
Heart failure physicians “are very good at disease-centered care” that focuses on survival and reducing hospitalizations, but “survival is often not as important to patients,” noted Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation program at St. Vincent Medical Group in Indianapolis. She suggested “tailoring treatment to improve patient symptoms, physical function, and quality of life” without necessarily reducing hospital readmissions or increasing survival rates. “Self-reported measures have more meaning for patients,” she said, and called for using PROs to better target interventions to the patients who can most benefit from them.
Two FDA representatives who spoke during the session agreed on the importance of PROs and attested to the agency’s interest in greater reliance on them.
“PROs are a critical complement to the other measures made in device trials,” said Bram Zuckerman, MD, director of the FDA’s division of cardiovascular devices. “We need PRO information because it reflects important aspects of patients’ health-related quality of life.”
The most commonly used PRO measures in device trials today are the Kansas City Cardiomyopathy Questionnaire (J Am Coll Cardiol. 2000 Apr;35[5]:1245-55) and the Minnesota Living With Heart Failure questionnaire, he noted.
“Neither is perfect, but there is a track record in heart failure device development that these two PROs can be helpful.” The FDA’s cardiovascular device division “wants to use PRO information,” Dr. Zuckerman said.
“All-cause mortality is the most unbiased endpoint, but there is interest in PROs,” agreed Ebony Dashiell-Aje, PhD, from the FDA’s office of new drugs in the Center for Drug Evaluation and Research. She highlighted the encouragement that the FDA gave to drug and device developers to include PROs in trials, both in its 2009 guidance document as well as in a “roadmap” from the agency on how to measure PROs in clinical trials. “Unfortunately, in heart failure we struggle to find tools that can adequately measure the patient’s perspective and be sensitive enough to detect a treatment benefit,” she said.
Norman Stockbridge, MD, director of the division of cardiovascular and renal products in the agency’s Office of Drug Evaluation, cited even bigger barriers to FDA approval of PROs as labeled effects from drugs or devices.
Getting a PRO endpoint supported by clinical-trial results that qualify it for an FDA label faces two big challenges. One challenge, he said, is “how much of an effect we need to see in a complex scoring algorithm to know that patients actually received some benefit in a disease that often varies from day to day and from week to week.” The second challenge is that, “in a disease with a high background rate of bad outcomes, you need some evidence that the benefit [from the treatment] is worth any risk,” which is something that can be hard to prove in heart failure when many patients don’t live more than 2 years with the disease, Dr. Stockbridge said in an interview.
“You need to be able to make the argument that the [PRO] benefit is likely perceptible to patients, but that is only half the problem. The other half is whether the developer can rule out that survival is not less than it would have been with no treatment. If patients take this, will they feel better but have a greater risk of being hurt?”
So far, no drug or device developer has succeeded in proving this to the FDA, despite the agency’s 2009 guidance on how it could be done.
That guidance “is one of the two worst and most destructive guidance documents we ever published,” Dr. Stockbridge declared.
Dr. Walsh, Dr. Heidenreich, Dr. Zuckerman, Dr. Dashiell-Aje, and Dr. Stockbridge had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM THE HFSA ANNUAL SCIENTIFIC MEETING
CardioMEMS shows real-world success as use expands
DALLAS – Management of outpatients with advanced heart failure using an implanted pulmonary artery pressure monitor continues to show real-world efficacy and safety at least as impressive as in the pivotal trial for the device.
Data from the first waves of patients to receive the CardioMEMS implanted pulmonary artery pressure (PAP) monitor since it got Food and Drug Administration marketing approval in May 2014 also showed steady uptake of this fluid volume management strategy for patients with advanced heart failure, despite Medicare reimbursement issues in some U.S. regions, J. Thomas Heywood, MD, said at the at the annual scientific meeting of the Heart Failure Society of America. He estimated that more than 6,000 U.S. heart failure patients have now had a CardioMEMS PAP monitor implanted.
“The clinicians using CardioMEMS now have a lot more experience” than they had during the trial, he said in an interview. “They have more experience using the device, they know what treatments to use to lower PAP more effectively, and they are now convinced that patients will benefit from reducing diastolic PAP.”
Dr. Heywood estimated that tens of thousands more U.S. heart failure patients with New York Heart Association class III disease and a recent history of at least one heart failure hospitalization are eligible to receive an implanted PAP monitor, dwarfing the more than 6,000 patients who received a device so far.
The postapproval study
The newest efficacy data come from the first 300 patients enrolled in the CardioMEMS HF System Post Approval Study, a registry of patients receiving an implanted PAP monitor funded by the device’s manufacturer and scheduled to include a total of 1,200 patients. Dr. Heywood said full enrollment was on track for completion by the end of October 2017.
The first 300 patients enrolled in the postapproval study were older than the CHAMPION cohort; they averaged about 69 years of age, compared with about 62 years in CHAMPION, were more often women (38% vs. 28% in CHAMPION), and were more likely to have heart failure with preserved ejection fraction (41% vs. about 22%).
A similar pattern existed for the 6-month cumulative tally of PAP area under the curve, which showed an average rise of 42 mm Hg/day in the CHAMPION control patients, an average drop of 160 mm Hg/day in the CHAMPION patients managed using their CardioMEMS data, and a drop of 281 mm Hg/day in the 300 postapproval study patients.
“We’re now using the implanted sensor in a broader population of patients, and one wonders whether the effect will be diluted. What we see is at least as good as in the CHAMPION trial. This is just an early snapshot, but it is exciting that we see no erosion of the benefit. It’s a great indication that the correct patients are receiving it,” Dr. Raval said while presenting a poster at the meeting.
Further scrutiny of the same 300 patients showed another feature of the impact of PAP monitoring on patient outcomes: The first 90 days with the PAP monitor in place led to a greater number of tweaks in patient treatment and a steady fall in PAP. During days 91-180, PAP tended to level off, the number of medication adjustments dropped, and heart failure hospitalizations fell even more than in the first 90 days, Joanna M. Joly, MD, reported in a separate poster at the meeting.
The data showed “effective reduction” of PAP during the second half of the study despite fewer medication adjustments. How was that possible? Patients who transmit data on their PAPs undergo “modeling of their behavior” based on the feedback they receive from the device, Dr. Joly suggested. Regular measurement of their PAP and seeing how the number relates to their clinical status helps patients “understand the impact of their nonadherence to diet and their medications.” Another factor could be the growing familiarity clinicians develop over time with PAP fluctuations that individual patients display repeatedly that are usually self-correcting. Also, patients may undergo “hemodynamic remodeling” that results in improved self-correction of minor shifts in fluid volume and vascular tone, she said.
This pattern of a reduced need for interventions after the first 90 days with a PAP implant suggests that many patients managed this way may be able to transition to care largely delivered by local providers, or even play a greater role in their own self-care once their PAP and clinical state stabilizes, Dr. Joly said.
The findings imply that by the end of the first 90 days, “patients accept the device and manage themselves better. It becomes basically a behavioral device” that helps patients better optimize their diet and behavior, Dr. Raval observed.
Safety holds steady
Continued real-world use of PAP monitoring has also resulted in new safety insights. During the first 3 years when the CardioMEMS device was on the U.S. market, May 2014–May 2017, the FDA’s adverse event reporting system for devices, the Manufacturer and User Facility Device Experience (MAUDE) received reports on 177 unique adverse events in 155 patients implanted with a PAP monitor, Muthiah Vaduganathan, MD, reported at the meeting. During the same 3-year period, he estimated that at least 5,500 U.S. patients had received a CardioMEMS device, based on data Dr. Vaduganathan obtained from the manufacturer, Abbott. This works out to an adverse event rate of about 2.8%, virtually identical to the rate reported from CHAMPION, noted Dr. Vaduganathan, a cardiologist also at Brigham and Women’s.
Analysis of both the 22 deaths as well as the episodes of pulmonary artery injury or hemoptysis showed that the preponderance occurred relatively early after introduction for U.S. use, suggesting that “a learning curve may exist for the most serious complications,” he said. “Improved safety and device durability may result from careful patient selection, increased operator training, and refined technologies.”
Dr. Vaduganathan cautioned that the MAUDE database is limited by its bias toward serious adverse events, selective reporting, and lack of adjudication for the reported events. Concurrently with his report at the meeting, a written version appeared online (JAMA Cardiol. 2017 Sep 18. doi:10.1001/jamacardio.2017.3791).
“The adverse event rate was reassuringly low, well below the accepted threshold for device safety. It bodes favorably for the device,” he said in an interview.
“But with a passive surveillance system like MAUDE, adverse events are likely underreported; we see in MAUDE the most severe adverse events. There is certainly a larger spectrum of more minor events that we are not seeing, but I think these numbers accurately reflect serious events.” A full registry of every U.S. patient who receives the device, similar to what’s in place for U.S. patients who undergo transcatheter aortic valve replacement, would provide a more complete picture of the risks, Dr. Vaduganathan suggested.
He also voiced some surprise about the frequency of pulmonary artery injury, which was not as apparent in the 550 total patients enrolled in CHAMPION. Clinicians who place the PAP monitor are required to first take a training program, but the manufacturer has no mandated minimum number of placements an operator must assist on before launching a new CardioMEMS practice, Dr. Vaduganathan said. Many of the pulmonary artery injuries reported to MAUDE resulted from wire perforations that resulted from loss of wire control, he noted.
Clarifying the optimal CardioMEMS recipients
PAP monitoring for patients with advanced heart failure “is a major advance for certain patients who have historically been very challenging to manage,” especially patients with heart failure with preserved ejection fraction, which has few other treatment options. But “it’s often difficult to know when to pull the trigger” and proceed with placing a PAP monitor in an eligible patient, he said. “Greater experience will help us better understand that,” Dr. Vaduganathan predicted.
Dr. Heywood said that, in addition to the standard criteria of NYHA class III symptoms and a recent history of a heart failure hospitalization, the other clinical feature he looks for in a patient who is a possible CardioMEMS recipient is a persistently elevated systolic PAP as measured using echocardiography.
“These are patients with evidence of an ongoing hemodynamic problem despite treatment, and I need more data to do a better job of getting their PAP down.” Although the PAP that patients self-measure once they have the device in place is their diastolic PAP, measuring systolic PAP by echo is usually a good surrogate for finding patients who also have a persistently elevated diastolic PAP, he explained.
Another important selection criterion is to look for the patients who are dying from heart failure rather than with heart failure, Dr. Heywood added.
“If heart failure is the major thing wrong, then we can improve their quality of life” by guiding fluid management with regular PAP measurement, especially patients with preserved left ventricular ejection fraction who have few other treatment options right now, he said.
The CardioMEMS HF System Post Approval Study is sponsored by Abbott, which markets CardioMEMS. Dr Heywood has been a consultant to and/or has received research funding from Abbott as well as Impedimed, Medtronic, Novartis, and Otsuka. Dr. Raval has been a consultant to Abbott. Dr. Joly and Dr. Vaduganathan had no disclosures.
[email protected]
On Twitter @mitchelzoler
DALLAS – Management of outpatients with advanced heart failure using an implanted pulmonary artery pressure monitor continues to show real-world efficacy and safety at least as impressive as in the pivotal trial for the device.
Data from the first waves of patients to receive the CardioMEMS implanted pulmonary artery pressure (PAP) monitor since it got Food and Drug Administration marketing approval in May 2014 also showed steady uptake of this fluid volume management strategy for patients with advanced heart failure, despite Medicare reimbursement issues in some U.S. regions, J. Thomas Heywood, MD, said at the at the annual scientific meeting of the Heart Failure Society of America. He estimated that more than 6,000 U.S. heart failure patients have now had a CardioMEMS PAP monitor implanted.
“The clinicians using CardioMEMS now have a lot more experience” than they had during the trial, he said in an interview. “They have more experience using the device, they know what treatments to use to lower PAP more effectively, and they are now convinced that patients will benefit from reducing diastolic PAP.”
Dr. Heywood estimated that tens of thousands more U.S. heart failure patients with New York Heart Association class III disease and a recent history of at least one heart failure hospitalization are eligible to receive an implanted PAP monitor, dwarfing the more than 6,000 patients who received a device so far.
The postapproval study
The newest efficacy data come from the first 300 patients enrolled in the CardioMEMS HF System Post Approval Study, a registry of patients receiving an implanted PAP monitor funded by the device’s manufacturer and scheduled to include a total of 1,200 patients. Dr. Heywood said full enrollment was on track for completion by the end of October 2017.
The first 300 patients enrolled in the postapproval study were older than the CHAMPION cohort; they averaged about 69 years of age, compared with about 62 years in CHAMPION, were more often women (38% vs. 28% in CHAMPION), and were more likely to have heart failure with preserved ejection fraction (41% vs. about 22%).
A similar pattern existed for the 6-month cumulative tally of PAP area under the curve, which showed an average rise of 42 mm Hg/day in the CHAMPION control patients, an average drop of 160 mm Hg/day in the CHAMPION patients managed using their CardioMEMS data, and a drop of 281 mm Hg/day in the 300 postapproval study patients.
“We’re now using the implanted sensor in a broader population of patients, and one wonders whether the effect will be diluted. What we see is at least as good as in the CHAMPION trial. This is just an early snapshot, but it is exciting that we see no erosion of the benefit. It’s a great indication that the correct patients are receiving it,” Dr. Raval said while presenting a poster at the meeting.
Further scrutiny of the same 300 patients showed another feature of the impact of PAP monitoring on patient outcomes: The first 90 days with the PAP monitor in place led to a greater number of tweaks in patient treatment and a steady fall in PAP. During days 91-180, PAP tended to level off, the number of medication adjustments dropped, and heart failure hospitalizations fell even more than in the first 90 days, Joanna M. Joly, MD, reported in a separate poster at the meeting.
The data showed “effective reduction” of PAP during the second half of the study despite fewer medication adjustments. How was that possible? Patients who transmit data on their PAPs undergo “modeling of their behavior” based on the feedback they receive from the device, Dr. Joly suggested. Regular measurement of their PAP and seeing how the number relates to their clinical status helps patients “understand the impact of their nonadherence to diet and their medications.” Another factor could be the growing familiarity clinicians develop over time with PAP fluctuations that individual patients display repeatedly that are usually self-correcting. Also, patients may undergo “hemodynamic remodeling” that results in improved self-correction of minor shifts in fluid volume and vascular tone, she said.
This pattern of a reduced need for interventions after the first 90 days with a PAP implant suggests that many patients managed this way may be able to transition to care largely delivered by local providers, or even play a greater role in their own self-care once their PAP and clinical state stabilizes, Dr. Joly said.
The findings imply that by the end of the first 90 days, “patients accept the device and manage themselves better. It becomes basically a behavioral device” that helps patients better optimize their diet and behavior, Dr. Raval observed.
Safety holds steady
Continued real-world use of PAP monitoring has also resulted in new safety insights. During the first 3 years when the CardioMEMS device was on the U.S. market, May 2014–May 2017, the FDA’s adverse event reporting system for devices, the Manufacturer and User Facility Device Experience (MAUDE) received reports on 177 unique adverse events in 155 patients implanted with a PAP monitor, Muthiah Vaduganathan, MD, reported at the meeting. During the same 3-year period, he estimated that at least 5,500 U.S. patients had received a CardioMEMS device, based on data Dr. Vaduganathan obtained from the manufacturer, Abbott. This works out to an adverse event rate of about 2.8%, virtually identical to the rate reported from CHAMPION, noted Dr. Vaduganathan, a cardiologist also at Brigham and Women’s.
Analysis of both the 22 deaths as well as the episodes of pulmonary artery injury or hemoptysis showed that the preponderance occurred relatively early after introduction for U.S. use, suggesting that “a learning curve may exist for the most serious complications,” he said. “Improved safety and device durability may result from careful patient selection, increased operator training, and refined technologies.”
Dr. Vaduganathan cautioned that the MAUDE database is limited by its bias toward serious adverse events, selective reporting, and lack of adjudication for the reported events. Concurrently with his report at the meeting, a written version appeared online (JAMA Cardiol. 2017 Sep 18. doi:10.1001/jamacardio.2017.3791).
“The adverse event rate was reassuringly low, well below the accepted threshold for device safety. It bodes favorably for the device,” he said in an interview.
“But with a passive surveillance system like MAUDE, adverse events are likely underreported; we see in MAUDE the most severe adverse events. There is certainly a larger spectrum of more minor events that we are not seeing, but I think these numbers accurately reflect serious events.” A full registry of every U.S. patient who receives the device, similar to what’s in place for U.S. patients who undergo transcatheter aortic valve replacement, would provide a more complete picture of the risks, Dr. Vaduganathan suggested.
He also voiced some surprise about the frequency of pulmonary artery injury, which was not as apparent in the 550 total patients enrolled in CHAMPION. Clinicians who place the PAP monitor are required to first take a training program, but the manufacturer has no mandated minimum number of placements an operator must assist on before launching a new CardioMEMS practice, Dr. Vaduganathan said. Many of the pulmonary artery injuries reported to MAUDE resulted from wire perforations that resulted from loss of wire control, he noted.
Clarifying the optimal CardioMEMS recipients
PAP monitoring for patients with advanced heart failure “is a major advance for certain patients who have historically been very challenging to manage,” especially patients with heart failure with preserved ejection fraction, which has few other treatment options. But “it’s often difficult to know when to pull the trigger” and proceed with placing a PAP monitor in an eligible patient, he said. “Greater experience will help us better understand that,” Dr. Vaduganathan predicted.
Dr. Heywood said that, in addition to the standard criteria of NYHA class III symptoms and a recent history of a heart failure hospitalization, the other clinical feature he looks for in a patient who is a possible CardioMEMS recipient is a persistently elevated systolic PAP as measured using echocardiography.
“These are patients with evidence of an ongoing hemodynamic problem despite treatment, and I need more data to do a better job of getting their PAP down.” Although the PAP that patients self-measure once they have the device in place is their diastolic PAP, measuring systolic PAP by echo is usually a good surrogate for finding patients who also have a persistently elevated diastolic PAP, he explained.
Another important selection criterion is to look for the patients who are dying from heart failure rather than with heart failure, Dr. Heywood added.
“If heart failure is the major thing wrong, then we can improve their quality of life” by guiding fluid management with regular PAP measurement, especially patients with preserved left ventricular ejection fraction who have few other treatment options right now, he said.
The CardioMEMS HF System Post Approval Study is sponsored by Abbott, which markets CardioMEMS. Dr Heywood has been a consultant to and/or has received research funding from Abbott as well as Impedimed, Medtronic, Novartis, and Otsuka. Dr. Raval has been a consultant to Abbott. Dr. Joly and Dr. Vaduganathan had no disclosures.
[email protected]
On Twitter @mitchelzoler
DALLAS – Management of outpatients with advanced heart failure using an implanted pulmonary artery pressure monitor continues to show real-world efficacy and safety at least as impressive as in the pivotal trial for the device.
Data from the first waves of patients to receive the CardioMEMS implanted pulmonary artery pressure (PAP) monitor since it got Food and Drug Administration marketing approval in May 2014 also showed steady uptake of this fluid volume management strategy for patients with advanced heart failure, despite Medicare reimbursement issues in some U.S. regions, J. Thomas Heywood, MD, said at the at the annual scientific meeting of the Heart Failure Society of America. He estimated that more than 6,000 U.S. heart failure patients have now had a CardioMEMS PAP monitor implanted.
“The clinicians using CardioMEMS now have a lot more experience” than they had during the trial, he said in an interview. “They have more experience using the device, they know what treatments to use to lower PAP more effectively, and they are now convinced that patients will benefit from reducing diastolic PAP.”
Dr. Heywood estimated that tens of thousands more U.S. heart failure patients with New York Heart Association class III disease and a recent history of at least one heart failure hospitalization are eligible to receive an implanted PAP monitor, dwarfing the more than 6,000 patients who received a device so far.
The postapproval study
The newest efficacy data come from the first 300 patients enrolled in the CardioMEMS HF System Post Approval Study, a registry of patients receiving an implanted PAP monitor funded by the device’s manufacturer and scheduled to include a total of 1,200 patients. Dr. Heywood said full enrollment was on track for completion by the end of October 2017.
The first 300 patients enrolled in the postapproval study were older than the CHAMPION cohort; they averaged about 69 years of age, compared with about 62 years in CHAMPION, were more often women (38% vs. 28% in CHAMPION), and were more likely to have heart failure with preserved ejection fraction (41% vs. about 22%).
A similar pattern existed for the 6-month cumulative tally of PAP area under the curve, which showed an average rise of 42 mm Hg/day in the CHAMPION control patients, an average drop of 160 mm Hg/day in the CHAMPION patients managed using their CardioMEMS data, and a drop of 281 mm Hg/day in the 300 postapproval study patients.
“We’re now using the implanted sensor in a broader population of patients, and one wonders whether the effect will be diluted. What we see is at least as good as in the CHAMPION trial. This is just an early snapshot, but it is exciting that we see no erosion of the benefit. It’s a great indication that the correct patients are receiving it,” Dr. Raval said while presenting a poster at the meeting.
Further scrutiny of the same 300 patients showed another feature of the impact of PAP monitoring on patient outcomes: The first 90 days with the PAP monitor in place led to a greater number of tweaks in patient treatment and a steady fall in PAP. During days 91-180, PAP tended to level off, the number of medication adjustments dropped, and heart failure hospitalizations fell even more than in the first 90 days, Joanna M. Joly, MD, reported in a separate poster at the meeting.
The data showed “effective reduction” of PAP during the second half of the study despite fewer medication adjustments. How was that possible? Patients who transmit data on their PAPs undergo “modeling of their behavior” based on the feedback they receive from the device, Dr. Joly suggested. Regular measurement of their PAP and seeing how the number relates to their clinical status helps patients “understand the impact of their nonadherence to diet and their medications.” Another factor could be the growing familiarity clinicians develop over time with PAP fluctuations that individual patients display repeatedly that are usually self-correcting. Also, patients may undergo “hemodynamic remodeling” that results in improved self-correction of minor shifts in fluid volume and vascular tone, she said.
This pattern of a reduced need for interventions after the first 90 days with a PAP implant suggests that many patients managed this way may be able to transition to care largely delivered by local providers, or even play a greater role in their own self-care once their PAP and clinical state stabilizes, Dr. Joly said.
The findings imply that by the end of the first 90 days, “patients accept the device and manage themselves better. It becomes basically a behavioral device” that helps patients better optimize their diet and behavior, Dr. Raval observed.
Safety holds steady
Continued real-world use of PAP monitoring has also resulted in new safety insights. During the first 3 years when the CardioMEMS device was on the U.S. market, May 2014–May 2017, the FDA’s adverse event reporting system for devices, the Manufacturer and User Facility Device Experience (MAUDE) received reports on 177 unique adverse events in 155 patients implanted with a PAP monitor, Muthiah Vaduganathan, MD, reported at the meeting. During the same 3-year period, he estimated that at least 5,500 U.S. patients had received a CardioMEMS device, based on data Dr. Vaduganathan obtained from the manufacturer, Abbott. This works out to an adverse event rate of about 2.8%, virtually identical to the rate reported from CHAMPION, noted Dr. Vaduganathan, a cardiologist also at Brigham and Women’s.
Analysis of both the 22 deaths as well as the episodes of pulmonary artery injury or hemoptysis showed that the preponderance occurred relatively early after introduction for U.S. use, suggesting that “a learning curve may exist for the most serious complications,” he said. “Improved safety and device durability may result from careful patient selection, increased operator training, and refined technologies.”
Dr. Vaduganathan cautioned that the MAUDE database is limited by its bias toward serious adverse events, selective reporting, and lack of adjudication for the reported events. Concurrently with his report at the meeting, a written version appeared online (JAMA Cardiol. 2017 Sep 18. doi:10.1001/jamacardio.2017.3791).
“The adverse event rate was reassuringly low, well below the accepted threshold for device safety. It bodes favorably for the device,” he said in an interview.
“But with a passive surveillance system like MAUDE, adverse events are likely underreported; we see in MAUDE the most severe adverse events. There is certainly a larger spectrum of more minor events that we are not seeing, but I think these numbers accurately reflect serious events.” A full registry of every U.S. patient who receives the device, similar to what’s in place for U.S. patients who undergo transcatheter aortic valve replacement, would provide a more complete picture of the risks, Dr. Vaduganathan suggested.
He also voiced some surprise about the frequency of pulmonary artery injury, which was not as apparent in the 550 total patients enrolled in CHAMPION. Clinicians who place the PAP monitor are required to first take a training program, but the manufacturer has no mandated minimum number of placements an operator must assist on before launching a new CardioMEMS practice, Dr. Vaduganathan said. Many of the pulmonary artery injuries reported to MAUDE resulted from wire perforations that resulted from loss of wire control, he noted.
Clarifying the optimal CardioMEMS recipients
PAP monitoring for patients with advanced heart failure “is a major advance for certain patients who have historically been very challenging to manage,” especially patients with heart failure with preserved ejection fraction, which has few other treatment options. But “it’s often difficult to know when to pull the trigger” and proceed with placing a PAP monitor in an eligible patient, he said. “Greater experience will help us better understand that,” Dr. Vaduganathan predicted.
Dr. Heywood said that, in addition to the standard criteria of NYHA class III symptoms and a recent history of a heart failure hospitalization, the other clinical feature he looks for in a patient who is a possible CardioMEMS recipient is a persistently elevated systolic PAP as measured using echocardiography.
“These are patients with evidence of an ongoing hemodynamic problem despite treatment, and I need more data to do a better job of getting their PAP down.” Although the PAP that patients self-measure once they have the device in place is their diastolic PAP, measuring systolic PAP by echo is usually a good surrogate for finding patients who also have a persistently elevated diastolic PAP, he explained.
Another important selection criterion is to look for the patients who are dying from heart failure rather than with heart failure, Dr. Heywood added.
“If heart failure is the major thing wrong, then we can improve their quality of life” by guiding fluid management with regular PAP measurement, especially patients with preserved left ventricular ejection fraction who have few other treatment options right now, he said.
The CardioMEMS HF System Post Approval Study is sponsored by Abbott, which markets CardioMEMS. Dr Heywood has been a consultant to and/or has received research funding from Abbott as well as Impedimed, Medtronic, Novartis, and Otsuka. Dr. Raval has been a consultant to Abbott. Dr. Joly and Dr. Vaduganathan had no disclosures.
[email protected]
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
MI, stroke risk from HFrEF surpasses HFpEF
DALLAS – Patients newly diagnosed with heart failure with reduced ejection fraction had about an 8% incidence of MIs during the subsequent 9 months, and a 5% incidence of ischemic strokes in a retrospective review of more than 1,600 community-dwelling U.S. patients.
The MI and ischemic stroke incidence rates in heart failure patients with reduced ejection fraction (HFrEF) were both significantly higher than in more than 4,000 patients with heart failure with preserved ejection fraction (HFpEF), Gregg C. Fonarow, MD, said while presenting a poster at the annual scientific meeting of the Heart Failure Society of America.
The findings suggest that greater attention is needed to reduce the risks for MI and stroke in HFrEF patients, suggested Dr. Fonarow, professor and cochief of cardiology at the University of California, Los Angeles, and his associates in their poster.
The study used claims data collected during July 2009-September 2016 from more than 10 million people enrolled in the United Health Group, who received care at more than 650 hospitals and about 6,600 clinics. The study included all patients diagnosed with heart failure during a hospital or emergency room visit and who had no history of a heart failure diagnosis or episode during the preceding 18 months, a left ventricular ejection fraction measurement made close to the time of the index encounter, and no stroke or MI apparent at the time of the index event. The study included 1,622 patients with HFrEF, defined as a left ventricular ejection fraction of less than 40%, 4,288 with HFpEF, defined as an ejection fraction of 50% or more, and 1,095 with heart failure with a borderline ejection fraction of 40%-49%.
The HFrEF patients had an average ejection fraction of 28%, they averaged 72 years old, 36% were women, and 8% had a prior stroke. The HFpEF patients averaged 74 years old, their average ejection fraction was 61%, 55% were women, and 11% had a prior stroke. Follow-up data on all patients were available for an average of nearly 9 months following their index heart failure event, with some patients followed as long as 1 year.
During follow-up, the incidence of ischemic stroke was 5.4% in the HFrEF patients and 3.9% in those with HFpEF, a difference that worked out to a statistically significant 40% higher ischemic stroke rate in HFrEF patients after adjustment for baseline differences between the two patient groups, Dr. Fonarow reported. The patients with a borderline ejection fraction had a 3.7% stroke incidence that fell short of a significant difference, compared with the HFrEF patient.The rate of new MIs during follow-up was 7.5% in the HFrEF patients and 3.2% in the HFpEF patients, a statistically significant 2.5-fold relatively higher MI rate with HFrEF, a statistically significant difference after adjustments. The MI incidence in patients with a borderline ejection fraction was 5.9%
[email protected]
On Twitter @mitchelzoler
DALLAS – Patients newly diagnosed with heart failure with reduced ejection fraction had about an 8% incidence of MIs during the subsequent 9 months, and a 5% incidence of ischemic strokes in a retrospective review of more than 1,600 community-dwelling U.S. patients.
The MI and ischemic stroke incidence rates in heart failure patients with reduced ejection fraction (HFrEF) were both significantly higher than in more than 4,000 patients with heart failure with preserved ejection fraction (HFpEF), Gregg C. Fonarow, MD, said while presenting a poster at the annual scientific meeting of the Heart Failure Society of America.
The findings suggest that greater attention is needed to reduce the risks for MI and stroke in HFrEF patients, suggested Dr. Fonarow, professor and cochief of cardiology at the University of California, Los Angeles, and his associates in their poster.
The study used claims data collected during July 2009-September 2016 from more than 10 million people enrolled in the United Health Group, who received care at more than 650 hospitals and about 6,600 clinics. The study included all patients diagnosed with heart failure during a hospital or emergency room visit and who had no history of a heart failure diagnosis or episode during the preceding 18 months, a left ventricular ejection fraction measurement made close to the time of the index encounter, and no stroke or MI apparent at the time of the index event. The study included 1,622 patients with HFrEF, defined as a left ventricular ejection fraction of less than 40%, 4,288 with HFpEF, defined as an ejection fraction of 50% or more, and 1,095 with heart failure with a borderline ejection fraction of 40%-49%.
The HFrEF patients had an average ejection fraction of 28%, they averaged 72 years old, 36% were women, and 8% had a prior stroke. The HFpEF patients averaged 74 years old, their average ejection fraction was 61%, 55% were women, and 11% had a prior stroke. Follow-up data on all patients were available for an average of nearly 9 months following their index heart failure event, with some patients followed as long as 1 year.
During follow-up, the incidence of ischemic stroke was 5.4% in the HFrEF patients and 3.9% in those with HFpEF, a difference that worked out to a statistically significant 40% higher ischemic stroke rate in HFrEF patients after adjustment for baseline differences between the two patient groups, Dr. Fonarow reported. The patients with a borderline ejection fraction had a 3.7% stroke incidence that fell short of a significant difference, compared with the HFrEF patient.The rate of new MIs during follow-up was 7.5% in the HFrEF patients and 3.2% in the HFpEF patients, a statistically significant 2.5-fold relatively higher MI rate with HFrEF, a statistically significant difference after adjustments. The MI incidence in patients with a borderline ejection fraction was 5.9%
[email protected]
On Twitter @mitchelzoler
DALLAS – Patients newly diagnosed with heart failure with reduced ejection fraction had about an 8% incidence of MIs during the subsequent 9 months, and a 5% incidence of ischemic strokes in a retrospective review of more than 1,600 community-dwelling U.S. patients.
The MI and ischemic stroke incidence rates in heart failure patients with reduced ejection fraction (HFrEF) were both significantly higher than in more than 4,000 patients with heart failure with preserved ejection fraction (HFpEF), Gregg C. Fonarow, MD, said while presenting a poster at the annual scientific meeting of the Heart Failure Society of America.
The findings suggest that greater attention is needed to reduce the risks for MI and stroke in HFrEF patients, suggested Dr. Fonarow, professor and cochief of cardiology at the University of California, Los Angeles, and his associates in their poster.
The study used claims data collected during July 2009-September 2016 from more than 10 million people enrolled in the United Health Group, who received care at more than 650 hospitals and about 6,600 clinics. The study included all patients diagnosed with heart failure during a hospital or emergency room visit and who had no history of a heart failure diagnosis or episode during the preceding 18 months, a left ventricular ejection fraction measurement made close to the time of the index encounter, and no stroke or MI apparent at the time of the index event. The study included 1,622 patients with HFrEF, defined as a left ventricular ejection fraction of less than 40%, 4,288 with HFpEF, defined as an ejection fraction of 50% or more, and 1,095 with heart failure with a borderline ejection fraction of 40%-49%.
The HFrEF patients had an average ejection fraction of 28%, they averaged 72 years old, 36% were women, and 8% had a prior stroke. The HFpEF patients averaged 74 years old, their average ejection fraction was 61%, 55% were women, and 11% had a prior stroke. Follow-up data on all patients were available for an average of nearly 9 months following their index heart failure event, with some patients followed as long as 1 year.
During follow-up, the incidence of ischemic stroke was 5.4% in the HFrEF patients and 3.9% in those with HFpEF, a difference that worked out to a statistically significant 40% higher ischemic stroke rate in HFrEF patients after adjustment for baseline differences between the two patient groups, Dr. Fonarow reported. The patients with a borderline ejection fraction had a 3.7% stroke incidence that fell short of a significant difference, compared with the HFrEF patient.The rate of new MIs during follow-up was 7.5% in the HFrEF patients and 3.2% in the HFpEF patients, a statistically significant 2.5-fold relatively higher MI rate with HFrEF, a statistically significant difference after adjustments. The MI incidence in patients with a borderline ejection fraction was 5.9%
[email protected]
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: HFrEF patients had a 40% higher incidence of stroke and a 2.5-fold higher incidence of MI, compared with HFpEF patients.
Data source: Retrospective review of 7,005 U.S. patients newly diagnosed with heart failure.
Disclosures: The study was funded by Janssen. Dr. Fonarow had no relevant disclosures.
VIDEO: Intermittent furosemide during acute HFpEF favors kidneys
DALLAS – Patients with heart failure with preserved ejection fraction who were hospitalized for acute decompensation had a significantly smaller rise in serum creatinine when treated with intermittent, bolus doses of furosemide, compared with patients who received a continuous furosemide infusion in a single-center, randomized trial with 90 patients.
Intermittent furosemide also resulted in many fewer episodes of worsening renal function. In the trial, 12% of patients who received bolus furosemide doses developed worsening renal function during hospitalization compared with 36% of patients treated with a continuous furosemide infusion, Kavita Sharma, MD, said at the annual scientific meeting of the Heart Failure Society of America.
While acknowledging that this finding is preliminary because it was made in a relatively small, single-center study, “I’d be cautious about continuous infusion” in acute decompensated patients with heart failure with preserved ejection fraction (HFpEF); “bolus is preferred,” Dr. Sharma said in a video interview.
Results from the prior Diuretic Optimization Strategies Evaluation (DOSE) trial, published in 2011, had shown no significant difference in renal function in hospitalized heart failure patients randomized to receive either bolus or continuous furosemide, but that study largely enrolled patients with heart failure with reduced ejection fraction (HFrEF) (N Engl J Med. 2011 Mar 3;364[9]:797-805).
“When patients with HFpEF are hospitalized with acute heart failure there is a high rate of kidney injury, that often results in slowing diuresis leading to longer hospital stays. With adjustment for changes in blood pressure and volume of diuresis we saw a fourfold increase in worsening renal failure [with continuous infusion], so you should think twice before using continuous dosing,” said Dr. Sharma, a heart failure cardiologist at Johns Hopkins Medicine in Baltimore.
She presented results from Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction (ROPA-DOP), which randomized 90 hospitalized heart failure patients with a left ventricular ejection fraction of at least 50% and an estimated glomerular filtration rate of more than 15 mL/min/1.73 m2. The enrolled patients averaged 66 years old, 61% were women, their average body mass index was 41 kg/m2, and their average estimated glomerular filtration rate was 58 mL/min/1.73 m2.
The study’s primary endpoint was percent change in creatinine during hospitalization, which rose by an average 5% in the patients who received intermittent bolus furosemide and by an average 16% in patient who received a continuous infusion, a statistically significant difference. In a regression analysis that controlled for between-group differences in patient’s age, sex, race, body mass index, smoking status, changes in systolic blood pressure, heart rate, fluid balance after 72 hours, and other variables, patients treated with continuous furosemide infusion averaged an 11% greater increase in serum creatinine, Dr. Sharma reported. After similar adjustments, the secondary endpoint rate of worsening renal function was more than four times more likely to occur in the patients on continuous infusion compared with those who received intermittent bolus treatment, she said.
A second aspect of the ROPA-DOP trial randomized the same patients to received either low dose (3 mcg/kg per min) dopamine or placebo during hospitalization. The results showed that low-dose dopamine had no significant impact on either change in creatinine levels or on the incidence of worsening renal function compared with placebo, though dopamine treatment did link with a nonsignificant trend toward somewhat greater diuresis. These results were consistent with prior findings in the Renal Optimization Strategies Evaluation (ROSE) trial (JAMA. 2013 Nov 18;310[23]:2533-43), which used a mixed population of patients with HFpEF or HFrEF but predominantly patients with HFrEF, Dr. Sharma noted.
“It was a neutral finding [for dopamine in ROPA-DOP], and while there was no harm from dopamine there was clearly no benefit,” she said. It is possible that HFpEF patients with right ventricular dysfunction secondary to pulmonary hypertension might benefit from low-dose dopamine, but this needs further study, Dr. Sharma said.
[email protected]
On Twitter @mitchelzoler
In the Diuretic Optimization Strategies Evaluation (DOSE) trial, we enrolled heart failure patients with a mix of reduced ejection fraction and preserved ejection fraction. The DOSE results showed no relationship between ejection fraction and the response to furosemide treatment by intermittent bolus or by continuous infusion in patients hospitalized with acute decompensated heart failure. The results also showed that continuous infusion was no better than intermittent bolus treatment, and following our report in 2011 (N Engl J Med. 2011 Mar 3;364[9]:797-805), many centers that had previously relied on continuous furosemide switched to use of bolus doses primarily because continuous infusion is much less convenient.
But it is important to keep in mind that trial results focus on averages and populations of patients. Anecdotally, we see some acute heart failure patients who seem to respond better to continuous infusion, and so some clinicians switch patients who do not respond well to bolus treatment to continuous infusion. In DOSE, we only tested the efficacy of the initial strategy; we have no evidence on whether or not changing the dosing strategy helps patients who do not respond adequately to an initial strategy of intermittent bolus doses.
G. Michael Felker, MD , professor of medicine at Duke University, Durham, N.C., made these comments in an interview. He has been a consultant to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, MyoKardia, Novartis, Stealth, and Trevena.
In the Diuretic Optimization Strategies Evaluation (DOSE) trial, we enrolled heart failure patients with a mix of reduced ejection fraction and preserved ejection fraction. The DOSE results showed no relationship between ejection fraction and the response to furosemide treatment by intermittent bolus or by continuous infusion in patients hospitalized with acute decompensated heart failure. The results also showed that continuous infusion was no better than intermittent bolus treatment, and following our report in 2011 (N Engl J Med. 2011 Mar 3;364[9]:797-805), many centers that had previously relied on continuous furosemide switched to use of bolus doses primarily because continuous infusion is much less convenient.
But it is important to keep in mind that trial results focus on averages and populations of patients. Anecdotally, we see some acute heart failure patients who seem to respond better to continuous infusion, and so some clinicians switch patients who do not respond well to bolus treatment to continuous infusion. In DOSE, we only tested the efficacy of the initial strategy; we have no evidence on whether or not changing the dosing strategy helps patients who do not respond adequately to an initial strategy of intermittent bolus doses.
G. Michael Felker, MD , professor of medicine at Duke University, Durham, N.C., made these comments in an interview. He has been a consultant to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, MyoKardia, Novartis, Stealth, and Trevena.
In the Diuretic Optimization Strategies Evaluation (DOSE) trial, we enrolled heart failure patients with a mix of reduced ejection fraction and preserved ejection fraction. The DOSE results showed no relationship between ejection fraction and the response to furosemide treatment by intermittent bolus or by continuous infusion in patients hospitalized with acute decompensated heart failure. The results also showed that continuous infusion was no better than intermittent bolus treatment, and following our report in 2011 (N Engl J Med. 2011 Mar 3;364[9]:797-805), many centers that had previously relied on continuous furosemide switched to use of bolus doses primarily because continuous infusion is much less convenient.
But it is important to keep in mind that trial results focus on averages and populations of patients. Anecdotally, we see some acute heart failure patients who seem to respond better to continuous infusion, and so some clinicians switch patients who do not respond well to bolus treatment to continuous infusion. In DOSE, we only tested the efficacy of the initial strategy; we have no evidence on whether or not changing the dosing strategy helps patients who do not respond adequately to an initial strategy of intermittent bolus doses.
G. Michael Felker, MD , professor of medicine at Duke University, Durham, N.C., made these comments in an interview. He has been a consultant to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, MyoKardia, Novartis, Stealth, and Trevena.
DALLAS – Patients with heart failure with preserved ejection fraction who were hospitalized for acute decompensation had a significantly smaller rise in serum creatinine when treated with intermittent, bolus doses of furosemide, compared with patients who received a continuous furosemide infusion in a single-center, randomized trial with 90 patients.
Intermittent furosemide also resulted in many fewer episodes of worsening renal function. In the trial, 12% of patients who received bolus furosemide doses developed worsening renal function during hospitalization compared with 36% of patients treated with a continuous furosemide infusion, Kavita Sharma, MD, said at the annual scientific meeting of the Heart Failure Society of America.
While acknowledging that this finding is preliminary because it was made in a relatively small, single-center study, “I’d be cautious about continuous infusion” in acute decompensated patients with heart failure with preserved ejection fraction (HFpEF); “bolus is preferred,” Dr. Sharma said in a video interview.
Results from the prior Diuretic Optimization Strategies Evaluation (DOSE) trial, published in 2011, had shown no significant difference in renal function in hospitalized heart failure patients randomized to receive either bolus or continuous furosemide, but that study largely enrolled patients with heart failure with reduced ejection fraction (HFrEF) (N Engl J Med. 2011 Mar 3;364[9]:797-805).
“When patients with HFpEF are hospitalized with acute heart failure there is a high rate of kidney injury, that often results in slowing diuresis leading to longer hospital stays. With adjustment for changes in blood pressure and volume of diuresis we saw a fourfold increase in worsening renal failure [with continuous infusion], so you should think twice before using continuous dosing,” said Dr. Sharma, a heart failure cardiologist at Johns Hopkins Medicine in Baltimore.
She presented results from Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction (ROPA-DOP), which randomized 90 hospitalized heart failure patients with a left ventricular ejection fraction of at least 50% and an estimated glomerular filtration rate of more than 15 mL/min/1.73 m2. The enrolled patients averaged 66 years old, 61% were women, their average body mass index was 41 kg/m2, and their average estimated glomerular filtration rate was 58 mL/min/1.73 m2.
The study’s primary endpoint was percent change in creatinine during hospitalization, which rose by an average 5% in the patients who received intermittent bolus furosemide and by an average 16% in patient who received a continuous infusion, a statistically significant difference. In a regression analysis that controlled for between-group differences in patient’s age, sex, race, body mass index, smoking status, changes in systolic blood pressure, heart rate, fluid balance after 72 hours, and other variables, patients treated with continuous furosemide infusion averaged an 11% greater increase in serum creatinine, Dr. Sharma reported. After similar adjustments, the secondary endpoint rate of worsening renal function was more than four times more likely to occur in the patients on continuous infusion compared with those who received intermittent bolus treatment, she said.
A second aspect of the ROPA-DOP trial randomized the same patients to received either low dose (3 mcg/kg per min) dopamine or placebo during hospitalization. The results showed that low-dose dopamine had no significant impact on either change in creatinine levels or on the incidence of worsening renal function compared with placebo, though dopamine treatment did link with a nonsignificant trend toward somewhat greater diuresis. These results were consistent with prior findings in the Renal Optimization Strategies Evaluation (ROSE) trial (JAMA. 2013 Nov 18;310[23]:2533-43), which used a mixed population of patients with HFpEF or HFrEF but predominantly patients with HFrEF, Dr. Sharma noted.
“It was a neutral finding [for dopamine in ROPA-DOP], and while there was no harm from dopamine there was clearly no benefit,” she said. It is possible that HFpEF patients with right ventricular dysfunction secondary to pulmonary hypertension might benefit from low-dose dopamine, but this needs further study, Dr. Sharma said.
[email protected]
On Twitter @mitchelzoler
DALLAS – Patients with heart failure with preserved ejection fraction who were hospitalized for acute decompensation had a significantly smaller rise in serum creatinine when treated with intermittent, bolus doses of furosemide, compared with patients who received a continuous furosemide infusion in a single-center, randomized trial with 90 patients.
Intermittent furosemide also resulted in many fewer episodes of worsening renal function. In the trial, 12% of patients who received bolus furosemide doses developed worsening renal function during hospitalization compared with 36% of patients treated with a continuous furosemide infusion, Kavita Sharma, MD, said at the annual scientific meeting of the Heart Failure Society of America.
While acknowledging that this finding is preliminary because it was made in a relatively small, single-center study, “I’d be cautious about continuous infusion” in acute decompensated patients with heart failure with preserved ejection fraction (HFpEF); “bolus is preferred,” Dr. Sharma said in a video interview.
Results from the prior Diuretic Optimization Strategies Evaluation (DOSE) trial, published in 2011, had shown no significant difference in renal function in hospitalized heart failure patients randomized to receive either bolus or continuous furosemide, but that study largely enrolled patients with heart failure with reduced ejection fraction (HFrEF) (N Engl J Med. 2011 Mar 3;364[9]:797-805).
“When patients with HFpEF are hospitalized with acute heart failure there is a high rate of kidney injury, that often results in slowing diuresis leading to longer hospital stays. With adjustment for changes in blood pressure and volume of diuresis we saw a fourfold increase in worsening renal failure [with continuous infusion], so you should think twice before using continuous dosing,” said Dr. Sharma, a heart failure cardiologist at Johns Hopkins Medicine in Baltimore.
She presented results from Diuretics and Dopamine in Heart Failure With Preserved Ejection Fraction (ROPA-DOP), which randomized 90 hospitalized heart failure patients with a left ventricular ejection fraction of at least 50% and an estimated glomerular filtration rate of more than 15 mL/min/1.73 m2. The enrolled patients averaged 66 years old, 61% were women, their average body mass index was 41 kg/m2, and their average estimated glomerular filtration rate was 58 mL/min/1.73 m2.
The study’s primary endpoint was percent change in creatinine during hospitalization, which rose by an average 5% in the patients who received intermittent bolus furosemide and by an average 16% in patient who received a continuous infusion, a statistically significant difference. In a regression analysis that controlled for between-group differences in patient’s age, sex, race, body mass index, smoking status, changes in systolic blood pressure, heart rate, fluid balance after 72 hours, and other variables, patients treated with continuous furosemide infusion averaged an 11% greater increase in serum creatinine, Dr. Sharma reported. After similar adjustments, the secondary endpoint rate of worsening renal function was more than four times more likely to occur in the patients on continuous infusion compared with those who received intermittent bolus treatment, she said.
A second aspect of the ROPA-DOP trial randomized the same patients to received either low dose (3 mcg/kg per min) dopamine or placebo during hospitalization. The results showed that low-dose dopamine had no significant impact on either change in creatinine levels or on the incidence of worsening renal function compared with placebo, though dopamine treatment did link with a nonsignificant trend toward somewhat greater diuresis. These results were consistent with prior findings in the Renal Optimization Strategies Evaluation (ROSE) trial (JAMA. 2013 Nov 18;310[23]:2533-43), which used a mixed population of patients with HFpEF or HFrEF but predominantly patients with HFrEF, Dr. Sharma noted.
“It was a neutral finding [for dopamine in ROPA-DOP], and while there was no harm from dopamine there was clearly no benefit,” she said. It is possible that HFpEF patients with right ventricular dysfunction secondary to pulmonary hypertension might benefit from low-dose dopamine, but this needs further study, Dr. Sharma said.
[email protected]
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: Serum creatinine rose by an average 5% with intermittent bolus furosemide and by 16% with continuous infusion.
Data source: ROPA-DOP, a single-center randomized trial with 90 patients.
Disclosures: Dr. Sharma had no disclosures.
Phrenic nerve stimulator shows heart failure benefits
DALLAS– Heart failure patients with central sleep apnea who received treatment with a transvenous phrenic nerve–stimulating device showed dramatic improvement in their global self-assessment, compared with control patients, in a subgroup analysis of 80 patients enrolled in the device’s pivotal trial.
Among 35 patients with heart failure enrolled in the remedē System pivotal trial and treated for 6 months with phrenic nerve stimulation, 57% reported that they had “markedly” or “moderately” improved, compared with a 9% rate for this self-rating among 44 control heart failure patients in the trial, a statistically significant difference, Lee R. Goldberg, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Further analysis focused on echocardiographic examinations after 12 months in 23 of the heart failure patients who entered the study with a left ventricular ejection fraction of 45% or less and received 12 months of phrenic nerve stimulation. The average LVEF rose in these patients from 30% at baseline to 35%, a statistically significant difference, and left ventricular end systolic volume fell by an average of almost 11 mL from baseline, a difference just short of statistical significance, findings Dr. Goldberg called “a little exciting.”
“It is very encouraging to see some evidence for ventricular remodeling,” commented Lynne W. Stevenson, MD, professor of medicine and a heart failure specialist at Vanderbilt University in Nashville, Tenn.
The FDA approved the use of this device for the treatment of moderate to severe central sleep apnea on Oct. 6. “I think we would use it” in heart failure patients with intolerable symptoms from central sleep apnea, Dr. Goldberg said in an interview during the meeting.
“There is a tight connection between sleep-disordered breathing, sleep apnea, heart failure, and cardiovascular disease, and we have been pretty aggressive in trying to treat the sleep apnea. Even if phrenic nerve stimulation just improves patients’ quality of life and is neutral for other outcomes,” it would be reasonable to offer it to patients, he said. “But many of us think there is a bigger connection that results in a therapeutic benefit [to heart failure patients] by treating their central sleep apnea.”
The pivotal trial enrolled a total of 151 patients with central sleep apnea at 31 centers in Germany, Poland, and the United States who were selected based on having an apnea-hypopnea index of at least 20 events per hour. All participants received a transvenous phrenic nerve–stimulator implant, and then randomization assigned 73 patients to have the device turned on for the first 6 months while 78 device recipients had their devices left off to serve as controls. The study’s primary efficacy endpoint was the percentage of patients having at least a 50% cut in their apnea-hypopnea index, which happened in 51% of evaluable patients in the active treatment arm and in 11% of the evaluable controls. The primary results were published last year (Lancet. 2016 Sep 3;388[10048]974-82).
“We hope this treatment will have the collateral effect of improving cardiovascular disease outcomes, but we don’t know that yet. The initial target will be patients with apnea-hypopnea episodes that affect their quality of life,” Dr. Goldberg said.
The apparent safety of this approach for treating central sleep apnea may relate to its mechanism of action, he suggested. The mortality-boosting effect of adaptive servo-ventilation may correlate with the positive pressure it creates in a patient’s chest that perhaps causes myocardial stress or hemodynamic problems. In contrast, phrenic nerve stimulation produces diaphragm motion that mimics normal breathing and creates negative chest pressure. “A lot of hypothesis generation needs to happen to better understand the underlying physiology,” Dr. Goldberg conceded.
At the end of the 6-month period that compared active treatment with control, the heart failure subgroup also showed statistically significant benefits from treatment for several sleep metrics, including apnea-hypopnea index, the central apnea index, and oxygen desaturation, and also for daytime sleepiness measured on the Epworth Sleepiness Scale. After 12 months on active treatment, patients also showed a significant improvement over baseline in their score on the Minnesota Living With Heart Failure Questionnaire, Dr. Goldberg reported.
The trial was sponsored by Respicardia, the company developing the remedē System. Dr. Goldberg has been a consultant to and has received research funding from Respicardia. Dr. Stevenson had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
DALLAS– Heart failure patients with central sleep apnea who received treatment with a transvenous phrenic nerve–stimulating device showed dramatic improvement in their global self-assessment, compared with control patients, in a subgroup analysis of 80 patients enrolled in the device’s pivotal trial.
Among 35 patients with heart failure enrolled in the remedē System pivotal trial and treated for 6 months with phrenic nerve stimulation, 57% reported that they had “markedly” or “moderately” improved, compared with a 9% rate for this self-rating among 44 control heart failure patients in the trial, a statistically significant difference, Lee R. Goldberg, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Further analysis focused on echocardiographic examinations after 12 months in 23 of the heart failure patients who entered the study with a left ventricular ejection fraction of 45% or less and received 12 months of phrenic nerve stimulation. The average LVEF rose in these patients from 30% at baseline to 35%, a statistically significant difference, and left ventricular end systolic volume fell by an average of almost 11 mL from baseline, a difference just short of statistical significance, findings Dr. Goldberg called “a little exciting.”
“It is very encouraging to see some evidence for ventricular remodeling,” commented Lynne W. Stevenson, MD, professor of medicine and a heart failure specialist at Vanderbilt University in Nashville, Tenn.
The FDA approved the use of this device for the treatment of moderate to severe central sleep apnea on Oct. 6. “I think we would use it” in heart failure patients with intolerable symptoms from central sleep apnea, Dr. Goldberg said in an interview during the meeting.
“There is a tight connection between sleep-disordered breathing, sleep apnea, heart failure, and cardiovascular disease, and we have been pretty aggressive in trying to treat the sleep apnea. Even if phrenic nerve stimulation just improves patients’ quality of life and is neutral for other outcomes,” it would be reasonable to offer it to patients, he said. “But many of us think there is a bigger connection that results in a therapeutic benefit [to heart failure patients] by treating their central sleep apnea.”
The pivotal trial enrolled a total of 151 patients with central sleep apnea at 31 centers in Germany, Poland, and the United States who were selected based on having an apnea-hypopnea index of at least 20 events per hour. All participants received a transvenous phrenic nerve–stimulator implant, and then randomization assigned 73 patients to have the device turned on for the first 6 months while 78 device recipients had their devices left off to serve as controls. The study’s primary efficacy endpoint was the percentage of patients having at least a 50% cut in their apnea-hypopnea index, which happened in 51% of evaluable patients in the active treatment arm and in 11% of the evaluable controls. The primary results were published last year (Lancet. 2016 Sep 3;388[10048]974-82).
“We hope this treatment will have the collateral effect of improving cardiovascular disease outcomes, but we don’t know that yet. The initial target will be patients with apnea-hypopnea episodes that affect their quality of life,” Dr. Goldberg said.
The apparent safety of this approach for treating central sleep apnea may relate to its mechanism of action, he suggested. The mortality-boosting effect of adaptive servo-ventilation may correlate with the positive pressure it creates in a patient’s chest that perhaps causes myocardial stress or hemodynamic problems. In contrast, phrenic nerve stimulation produces diaphragm motion that mimics normal breathing and creates negative chest pressure. “A lot of hypothesis generation needs to happen to better understand the underlying physiology,” Dr. Goldberg conceded.
At the end of the 6-month period that compared active treatment with control, the heart failure subgroup also showed statistically significant benefits from treatment for several sleep metrics, including apnea-hypopnea index, the central apnea index, and oxygen desaturation, and also for daytime sleepiness measured on the Epworth Sleepiness Scale. After 12 months on active treatment, patients also showed a significant improvement over baseline in their score on the Minnesota Living With Heart Failure Questionnaire, Dr. Goldberg reported.
The trial was sponsored by Respicardia, the company developing the remedē System. Dr. Goldberg has been a consultant to and has received research funding from Respicardia. Dr. Stevenson had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
DALLAS– Heart failure patients with central sleep apnea who received treatment with a transvenous phrenic nerve–stimulating device showed dramatic improvement in their global self-assessment, compared with control patients, in a subgroup analysis of 80 patients enrolled in the device’s pivotal trial.
Among 35 patients with heart failure enrolled in the remedē System pivotal trial and treated for 6 months with phrenic nerve stimulation, 57% reported that they had “markedly” or “moderately” improved, compared with a 9% rate for this self-rating among 44 control heart failure patients in the trial, a statistically significant difference, Lee R. Goldberg, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Further analysis focused on echocardiographic examinations after 12 months in 23 of the heart failure patients who entered the study with a left ventricular ejection fraction of 45% or less and received 12 months of phrenic nerve stimulation. The average LVEF rose in these patients from 30% at baseline to 35%, a statistically significant difference, and left ventricular end systolic volume fell by an average of almost 11 mL from baseline, a difference just short of statistical significance, findings Dr. Goldberg called “a little exciting.”
“It is very encouraging to see some evidence for ventricular remodeling,” commented Lynne W. Stevenson, MD, professor of medicine and a heart failure specialist at Vanderbilt University in Nashville, Tenn.
The FDA approved the use of this device for the treatment of moderate to severe central sleep apnea on Oct. 6. “I think we would use it” in heart failure patients with intolerable symptoms from central sleep apnea, Dr. Goldberg said in an interview during the meeting.
“There is a tight connection between sleep-disordered breathing, sleep apnea, heart failure, and cardiovascular disease, and we have been pretty aggressive in trying to treat the sleep apnea. Even if phrenic nerve stimulation just improves patients’ quality of life and is neutral for other outcomes,” it would be reasonable to offer it to patients, he said. “But many of us think there is a bigger connection that results in a therapeutic benefit [to heart failure patients] by treating their central sleep apnea.”
The pivotal trial enrolled a total of 151 patients with central sleep apnea at 31 centers in Germany, Poland, and the United States who were selected based on having an apnea-hypopnea index of at least 20 events per hour. All participants received a transvenous phrenic nerve–stimulator implant, and then randomization assigned 73 patients to have the device turned on for the first 6 months while 78 device recipients had their devices left off to serve as controls. The study’s primary efficacy endpoint was the percentage of patients having at least a 50% cut in their apnea-hypopnea index, which happened in 51% of evaluable patients in the active treatment arm and in 11% of the evaluable controls. The primary results were published last year (Lancet. 2016 Sep 3;388[10048]974-82).
“We hope this treatment will have the collateral effect of improving cardiovascular disease outcomes, but we don’t know that yet. The initial target will be patients with apnea-hypopnea episodes that affect their quality of life,” Dr. Goldberg said.
The apparent safety of this approach for treating central sleep apnea may relate to its mechanism of action, he suggested. The mortality-boosting effect of adaptive servo-ventilation may correlate with the positive pressure it creates in a patient’s chest that perhaps causes myocardial stress or hemodynamic problems. In contrast, phrenic nerve stimulation produces diaphragm motion that mimics normal breathing and creates negative chest pressure. “A lot of hypothesis generation needs to happen to better understand the underlying physiology,” Dr. Goldberg conceded.
At the end of the 6-month period that compared active treatment with control, the heart failure subgroup also showed statistically significant benefits from treatment for several sleep metrics, including apnea-hypopnea index, the central apnea index, and oxygen desaturation, and also for daytime sleepiness measured on the Epworth Sleepiness Scale. After 12 months on active treatment, patients also showed a significant improvement over baseline in their score on the Minnesota Living With Heart Failure Questionnaire, Dr. Goldberg reported.
The trial was sponsored by Respicardia, the company developing the remedē System. Dr. Goldberg has been a consultant to and has received research funding from Respicardia. Dr. Stevenson had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: Patient-reported global assessment improved markedly or moderately in 57% of treated patients and in 9% of controls.
Data source: Subgroup analysis of the remedē System pivotal trial.
Disclosures: The trial was sponsored by Respicardia, the company developing the remedē System. Dr. Goldberg has been a consultant to and has received research funding from Respicardia. Dr. Stevenson had no relevant disclosures.
Carpal tunnel syndrome may flag cardiac amyloidosis in elderly
DALLAS – Older patients with carpal tunnel syndrome that requires release surgery appear to have a relatively high prevalence of amyloidosis that, in some, involves their heart, suggesting that routine screening for amyloidosis is warranted in elderly patients undergoing the surgery.
Routine Congo red staining of a tenosynovial biopsy taken at the time of carpal tunnel release surgery in a single-center experience with 96 patients showed that 10 (10%) were positive for amyloidosis, Mazen Hanna, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Clinicians “should be aware of the association between carpal tunnel syndrome [CTS] and amyloidosis.” When a 60-year old shows up with bilateral CTS without a clear cause, it’s reasonable to suspect amyloidosis, he suggested.
The prospective study run by Dr. Hanna and his associates included men at least 50 years old and women at least 60 years old who underwent CTS release surgery at the Cleveland Clinic during May 2016–June 2017. Enrollment excluded patients with known amyloidosis or rheumatoid arthritis. The patients averaged 68 years of age, 51% were men, and 85% had bilateral CTS that required surgery. The surgeons removed a tenosynovial biopsy at the time of surgery from each of the 96 patients, a “low-risk procedure,” Dr. Hanna said.
The 10 patients with positive staining for amyloid underwent a work-up that included a comprehensive physical examination, a series of blood tests for cardiac biomarkers, an ECG, echocardiography including assessment of cardiac strain, and a technetium-99m pyrophosphate scan. This identified two patients with cardiac involvement. The examinations identified one case by the echocardiographic strain findings and the second case by the technetium pyrophosphate scan. Seven of the 10 patients with amyloid had a history of prior carpal tunnel release surgery.
The researchers also used mass spectroscopy to identify the amyloid type. Seven patients had the transthyretin subtype, including one patient with cardiac involvement; two patients had light chain amyloidosis, including the second patient with cardiac involvement. The tenth patient had inconclusive results but the researchers presumed the amyloid was of the transthyretin type, Dr. Hanna said.
The eight patients identified with amyloid but no cardiac involvement at baseline will continue to receive annual work ups to see whether their hearts become affected over time. The protocol delays a repeat technetium pyrophosphate scan until the 4th year following study entry.
The potential usefulness of early identification and treatment of cardiac amyloidosis received support in results from another study reported at the meeting. Researchers from Columbia University Medical Center, New York, and New York Presbyterian Hospital reported their retrospective, nonrandomized experience with 126 patients who had been diagnosed with transthyretin cardiac amyloidosis. Thirty of these patients had received treatment with a transthyretin-stabilizing drug, either the investigational agent tafamidis or diflunisal, while the other 96 patients received no stabilizing treatment. During a median follow-up of 2 years, patients treated with a stabilizing agent had a statistically significant 68% reduced rate of either death or orthotopic heart transplant, compared with the untreated patients in a multivariate analysis that controlled for various baseline differences between the treated and untreated patients.
[email protected]
On Twitter @mitchelzoler
DALLAS – Older patients with carpal tunnel syndrome that requires release surgery appear to have a relatively high prevalence of amyloidosis that, in some, involves their heart, suggesting that routine screening for amyloidosis is warranted in elderly patients undergoing the surgery.
Routine Congo red staining of a tenosynovial biopsy taken at the time of carpal tunnel release surgery in a single-center experience with 96 patients showed that 10 (10%) were positive for amyloidosis, Mazen Hanna, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Clinicians “should be aware of the association between carpal tunnel syndrome [CTS] and amyloidosis.” When a 60-year old shows up with bilateral CTS without a clear cause, it’s reasonable to suspect amyloidosis, he suggested.
The prospective study run by Dr. Hanna and his associates included men at least 50 years old and women at least 60 years old who underwent CTS release surgery at the Cleveland Clinic during May 2016–June 2017. Enrollment excluded patients with known amyloidosis or rheumatoid arthritis. The patients averaged 68 years of age, 51% were men, and 85% had bilateral CTS that required surgery. The surgeons removed a tenosynovial biopsy at the time of surgery from each of the 96 patients, a “low-risk procedure,” Dr. Hanna said.
The 10 patients with positive staining for amyloid underwent a work-up that included a comprehensive physical examination, a series of blood tests for cardiac biomarkers, an ECG, echocardiography including assessment of cardiac strain, and a technetium-99m pyrophosphate scan. This identified two patients with cardiac involvement. The examinations identified one case by the echocardiographic strain findings and the second case by the technetium pyrophosphate scan. Seven of the 10 patients with amyloid had a history of prior carpal tunnel release surgery.
The researchers also used mass spectroscopy to identify the amyloid type. Seven patients had the transthyretin subtype, including one patient with cardiac involvement; two patients had light chain amyloidosis, including the second patient with cardiac involvement. The tenth patient had inconclusive results but the researchers presumed the amyloid was of the transthyretin type, Dr. Hanna said.
The eight patients identified with amyloid but no cardiac involvement at baseline will continue to receive annual work ups to see whether their hearts become affected over time. The protocol delays a repeat technetium pyrophosphate scan until the 4th year following study entry.
The potential usefulness of early identification and treatment of cardiac amyloidosis received support in results from another study reported at the meeting. Researchers from Columbia University Medical Center, New York, and New York Presbyterian Hospital reported their retrospective, nonrandomized experience with 126 patients who had been diagnosed with transthyretin cardiac amyloidosis. Thirty of these patients had received treatment with a transthyretin-stabilizing drug, either the investigational agent tafamidis or diflunisal, while the other 96 patients received no stabilizing treatment. During a median follow-up of 2 years, patients treated with a stabilizing agent had a statistically significant 68% reduced rate of either death or orthotopic heart transplant, compared with the untreated patients in a multivariate analysis that controlled for various baseline differences between the treated and untreated patients.
[email protected]
On Twitter @mitchelzoler
DALLAS – Older patients with carpal tunnel syndrome that requires release surgery appear to have a relatively high prevalence of amyloidosis that, in some, involves their heart, suggesting that routine screening for amyloidosis is warranted in elderly patients undergoing the surgery.
Routine Congo red staining of a tenosynovial biopsy taken at the time of carpal tunnel release surgery in a single-center experience with 96 patients showed that 10 (10%) were positive for amyloidosis, Mazen Hanna, MD, said at the annual scientific meeting of the Heart Failure Society of America.
Clinicians “should be aware of the association between carpal tunnel syndrome [CTS] and amyloidosis.” When a 60-year old shows up with bilateral CTS without a clear cause, it’s reasonable to suspect amyloidosis, he suggested.
The prospective study run by Dr. Hanna and his associates included men at least 50 years old and women at least 60 years old who underwent CTS release surgery at the Cleveland Clinic during May 2016–June 2017. Enrollment excluded patients with known amyloidosis or rheumatoid arthritis. The patients averaged 68 years of age, 51% were men, and 85% had bilateral CTS that required surgery. The surgeons removed a tenosynovial biopsy at the time of surgery from each of the 96 patients, a “low-risk procedure,” Dr. Hanna said.
The 10 patients with positive staining for amyloid underwent a work-up that included a comprehensive physical examination, a series of blood tests for cardiac biomarkers, an ECG, echocardiography including assessment of cardiac strain, and a technetium-99m pyrophosphate scan. This identified two patients with cardiac involvement. The examinations identified one case by the echocardiographic strain findings and the second case by the technetium pyrophosphate scan. Seven of the 10 patients with amyloid had a history of prior carpal tunnel release surgery.
The researchers also used mass spectroscopy to identify the amyloid type. Seven patients had the transthyretin subtype, including one patient with cardiac involvement; two patients had light chain amyloidosis, including the second patient with cardiac involvement. The tenth patient had inconclusive results but the researchers presumed the amyloid was of the transthyretin type, Dr. Hanna said.
The eight patients identified with amyloid but no cardiac involvement at baseline will continue to receive annual work ups to see whether their hearts become affected over time. The protocol delays a repeat technetium pyrophosphate scan until the 4th year following study entry.
The potential usefulness of early identification and treatment of cardiac amyloidosis received support in results from another study reported at the meeting. Researchers from Columbia University Medical Center, New York, and New York Presbyterian Hospital reported their retrospective, nonrandomized experience with 126 patients who had been diagnosed with transthyretin cardiac amyloidosis. Thirty of these patients had received treatment with a transthyretin-stabilizing drug, either the investigational agent tafamidis or diflunisal, while the other 96 patients received no stabilizing treatment. During a median follow-up of 2 years, patients treated with a stabilizing agent had a statistically significant 68% reduced rate of either death or orthotopic heart transplant, compared with the untreated patients in a multivariate analysis that controlled for various baseline differences between the treated and untreated patients.
[email protected]
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: Ten of 96 patients undergoing carpal tunnel release surgery had amyloidosis, and two had cardiac involvement.
Data source: Prospective, single-center series of 96 patients undergoing carpal tunnel release surgery.
Disclosures: Dr. Hanna had no disclosures.
LVAD use soars in elderly Americans
DALLAS – The percentage of left ventricular assist devices placed in U.S. heart failure patients at least 75 years of age jumped sharply during 2003-2014, and concurrently the short-term survival of these patients improved dramatically, according to data collected by the National Inpatient Sample.
During the 12-year period examined, the percentage of left-ventricular assist devices (LVADs) placed in U.S. heart failure patients aged 75 years and older rose from 3% of all LVADs in 2003 to 11% in 2014, Aniket S. Rali, MD, said at the annual scientific meeting of the Heart Failure Society of America.
The U.S. national numbers also showed that throughout the period studied, elderly U.S. patients who received an LVAD were increasingly sicker, with steadily increasing numbers of patients with a Charlson Comorbidity Index score of four or greater. Despite this, in-hospital mortality rates of elderly patients receiving an LVAD plummeted, dropping from 61% of elderly LVAD recipients in 2003 to 18% in 2014. During the same time, the percentage of elderly patients with a Charlson Comorbidity Index score greater than four doubled from 33% in 2003 to 66% in 2014, said Dr. Rali, a cardiologist at the University of Kansas Medical Center in Kansas City.
“If the Charlson Comorbidity Index score is increasing but in-hospital mortality is decreasing, then increased LVAD use is not a bad trend,” Dr. Rali said in an interview. He hopes that future analysis of longitudinal data from patients could identify clinical factors that link with better patient survival and help target LVAD placement to the patients who stand to gain the most benefit.
“We may be able to give these elderly patients not just longer life but improved quality of life” by a more informed targeting of LVADs, he suggested. “I think these numbers will help convince people that all is not lost,” he noted, for elderly heart failure patients who receive an LVAD as destination therapy. Patients at least 75 years old are not eligible for heart transplantation, so when these patients receive an LVAD it is, by definition, destination therapy.
The data also showed a marked sex disparity in LVAD use, with LVAD placement in men at least 75 years old rising from 1.4/1,000 patients in 2003 to 2.78/1,000 patients in 2014. In contrast, among women these rates rose from 0.8/1,000 patients in 2003 to 1.36/1,000 patients in 2014.
The average age for elderly U.S. LVAD recipients for the entire 12-year period studied was 77.6 years among a total of 2,090 recipients. For all 21,323 U.S. LVAD recipients during 2003-2014 the average age was 51.5 years old.
[email protected]
On Twitter @mitchelzoler
DALLAS – The percentage of left ventricular assist devices placed in U.S. heart failure patients at least 75 years of age jumped sharply during 2003-2014, and concurrently the short-term survival of these patients improved dramatically, according to data collected by the National Inpatient Sample.
During the 12-year period examined, the percentage of left-ventricular assist devices (LVADs) placed in U.S. heart failure patients aged 75 years and older rose from 3% of all LVADs in 2003 to 11% in 2014, Aniket S. Rali, MD, said at the annual scientific meeting of the Heart Failure Society of America.
The U.S. national numbers also showed that throughout the period studied, elderly U.S. patients who received an LVAD were increasingly sicker, with steadily increasing numbers of patients with a Charlson Comorbidity Index score of four or greater. Despite this, in-hospital mortality rates of elderly patients receiving an LVAD plummeted, dropping from 61% of elderly LVAD recipients in 2003 to 18% in 2014. During the same time, the percentage of elderly patients with a Charlson Comorbidity Index score greater than four doubled from 33% in 2003 to 66% in 2014, said Dr. Rali, a cardiologist at the University of Kansas Medical Center in Kansas City.
“If the Charlson Comorbidity Index score is increasing but in-hospital mortality is decreasing, then increased LVAD use is not a bad trend,” Dr. Rali said in an interview. He hopes that future analysis of longitudinal data from patients could identify clinical factors that link with better patient survival and help target LVAD placement to the patients who stand to gain the most benefit.
“We may be able to give these elderly patients not just longer life but improved quality of life” by a more informed targeting of LVADs, he suggested. “I think these numbers will help convince people that all is not lost,” he noted, for elderly heart failure patients who receive an LVAD as destination therapy. Patients at least 75 years old are not eligible for heart transplantation, so when these patients receive an LVAD it is, by definition, destination therapy.
The data also showed a marked sex disparity in LVAD use, with LVAD placement in men at least 75 years old rising from 1.4/1,000 patients in 2003 to 2.78/1,000 patients in 2014. In contrast, among women these rates rose from 0.8/1,000 patients in 2003 to 1.36/1,000 patients in 2014.
The average age for elderly U.S. LVAD recipients for the entire 12-year period studied was 77.6 years among a total of 2,090 recipients. For all 21,323 U.S. LVAD recipients during 2003-2014 the average age was 51.5 years old.
[email protected]
On Twitter @mitchelzoler
DALLAS – The percentage of left ventricular assist devices placed in U.S. heart failure patients at least 75 years of age jumped sharply during 2003-2014, and concurrently the short-term survival of these patients improved dramatically, according to data collected by the National Inpatient Sample.
During the 12-year period examined, the percentage of left-ventricular assist devices (LVADs) placed in U.S. heart failure patients aged 75 years and older rose from 3% of all LVADs in 2003 to 11% in 2014, Aniket S. Rali, MD, said at the annual scientific meeting of the Heart Failure Society of America.
The U.S. national numbers also showed that throughout the period studied, elderly U.S. patients who received an LVAD were increasingly sicker, with steadily increasing numbers of patients with a Charlson Comorbidity Index score of four or greater. Despite this, in-hospital mortality rates of elderly patients receiving an LVAD plummeted, dropping from 61% of elderly LVAD recipients in 2003 to 18% in 2014. During the same time, the percentage of elderly patients with a Charlson Comorbidity Index score greater than four doubled from 33% in 2003 to 66% in 2014, said Dr. Rali, a cardiologist at the University of Kansas Medical Center in Kansas City.
“If the Charlson Comorbidity Index score is increasing but in-hospital mortality is decreasing, then increased LVAD use is not a bad trend,” Dr. Rali said in an interview. He hopes that future analysis of longitudinal data from patients could identify clinical factors that link with better patient survival and help target LVAD placement to the patients who stand to gain the most benefit.
“We may be able to give these elderly patients not just longer life but improved quality of life” by a more informed targeting of LVADs, he suggested. “I think these numbers will help convince people that all is not lost,” he noted, for elderly heart failure patients who receive an LVAD as destination therapy. Patients at least 75 years old are not eligible for heart transplantation, so when these patients receive an LVAD it is, by definition, destination therapy.
The data also showed a marked sex disparity in LVAD use, with LVAD placement in men at least 75 years old rising from 1.4/1,000 patients in 2003 to 2.78/1,000 patients in 2014. In contrast, among women these rates rose from 0.8/1,000 patients in 2003 to 1.36/1,000 patients in 2014.
The average age for elderly U.S. LVAD recipients for the entire 12-year period studied was 77.6 years among a total of 2,090 recipients. For all 21,323 U.S. LVAD recipients during 2003-2014 the average age was 51.5 years old.
[email protected]
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: Elderly U.S. patients receiving an LVAD rose from 3% of all LVADs placed in 2003 to 11% in 2014.
Data source: The U.S. National Inpatient Survey during 2003-2014.
Disclosures: Dr. Rali had no disclosures.
While U.S. heart failure readmissions fall, deaths rise
DALLAS – U.S. hospitals have recently shown a consistent and disturbing disconnect between reductions in their heart failure hospital readmission rates and heart failure mortality. Readmissions have dropped while mortality has risen.
“Despite reductions in 30-day heart failure readmissions in 89% of U.S. hospitals” during 2009-2016, “30-day heart failure mortality rates increased at 73%* of these ‘successful’ hospitals” during the same period,” Ahmad A. Abdul-Aziz, MD, said at the annual scientific meeting of the Heart Failure Society of America.
These shifts in the outcomes of U.S. patients hospitalized for acute heart failure episodes are tied to the penalties that the Centers for Medicare & Medicaid Services began slapping on hospitals in 2013 for excess 30-day readmissions for heart failure patients and in 2014 for excess mortality. A problem with these two CMS programs is that the penalty on inferior readmissions performance is a lot stiffer than for excess mortality, Dr. Aziz noted: a 0.2% penalty on payments for high mortality, compared with a 3% penalty for excess readmissions, a disparity that can make hospitals focus more on the readmissions side, he suggested.
Dr. Aziz’s report isn’t the first to make this observation. Study results published earlier in 2017 used CMS Medicare data from 2008 to 2014 to show that during that period, heart failure 30-day mortality rates following hospital discharge rose by 1.3%, while 30-day readmissions fell by 2.1% (JAMA. 2017 July 18;318[3]:270-8). On the basis of these numbers, as many as 5,200 additional deaths to U.S. heart failure patients in 2014 “may be related to the Hospital Readmission Reduction Program” of CMS, Gregg C. Fonarow, MD, said during a separate talk at the meeting.
The analysis reported by Dr. Aziz included data from 3,265 U.S. hospitals for heart failure patients, and data from 1,621 hospitals that managed patients with acute MIs, another disease that the CMS has targeted for penalties based on 30-day readmissions and 30-day postdischarge mortality rates. During the 8-year period studied, heart failure 30-day readmissions fell by 2.2% while 30-day mortality rose by 1%. In contrast, among acute MI patients, readmissions fell by 3% and mortality also fell, by 2.2%, Dr. Abdul-Aziz reported.
Dr. Abdul-Aziz had no disclosures. Dr. Fonarow had been a consultant to Amgen, Janssen, Medtronic, Novartis, St. Jude, and ZS Pharma.
[email protected]
On Twitter @mitchelzoler
*This article was updated October 5, 2017
My colleagues and I have seen in results from recent trials a changing relationship between heart failure mortality and heart failure hospitalization. In the United States in particular, where penalties exist for high rates of hospital readmissions for heart failure, we are seeing more patients treated as outpatients and we see that these “outpatient” events are associated with the same risk for subsequent mortality as we had previously seen for heart failure hospitalization.
It may be that we are keeping patients out of the hospital to avoid a financial ding, but perhaps we are keeping out patients who really should be hospitalized.
What we have begun doing in trials is to look not just at hospitalizations but also consider the incidence of other heart failure events, such as patients treated for heart failure symptoms with an intravenous diuretic in the emergency department and patients who are kept in observation rooms and are not admitted. It’s not the same as a heart failure hospitalization, but some trials are now including these other heart failure events in their primary endpoint.
Scott D. Solomon, MD, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital in Boston, made these comments as chair of the session where Dr. Aziz gave his report and in an interview. He has been a consultant to and/or received research support from Alnylam, Amgen, AstraZeneca, Bristol-Myers Squibb, Cytokinetics, GlaxoSmithKline, Ionis, Merck, Novartis, and Sanofi.
My colleagues and I have seen in results from recent trials a changing relationship between heart failure mortality and heart failure hospitalization. In the United States in particular, where penalties exist for high rates of hospital readmissions for heart failure, we are seeing more patients treated as outpatients and we see that these “outpatient” events are associated with the same risk for subsequent mortality as we had previously seen for heart failure hospitalization.
It may be that we are keeping patients out of the hospital to avoid a financial ding, but perhaps we are keeping out patients who really should be hospitalized.
What we have begun doing in trials is to look not just at hospitalizations but also consider the incidence of other heart failure events, such as patients treated for heart failure symptoms with an intravenous diuretic in the emergency department and patients who are kept in observation rooms and are not admitted. It’s not the same as a heart failure hospitalization, but some trials are now including these other heart failure events in their primary endpoint.
Scott D. Solomon, MD, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital in Boston, made these comments as chair of the session where Dr. Aziz gave his report and in an interview. He has been a consultant to and/or received research support from Alnylam, Amgen, AstraZeneca, Bristol-Myers Squibb, Cytokinetics, GlaxoSmithKline, Ionis, Merck, Novartis, and Sanofi.
My colleagues and I have seen in results from recent trials a changing relationship between heart failure mortality and heart failure hospitalization. In the United States in particular, where penalties exist for high rates of hospital readmissions for heart failure, we are seeing more patients treated as outpatients and we see that these “outpatient” events are associated with the same risk for subsequent mortality as we had previously seen for heart failure hospitalization.
It may be that we are keeping patients out of the hospital to avoid a financial ding, but perhaps we are keeping out patients who really should be hospitalized.
What we have begun doing in trials is to look not just at hospitalizations but also consider the incidence of other heart failure events, such as patients treated for heart failure symptoms with an intravenous diuretic in the emergency department and patients who are kept in observation rooms and are not admitted. It’s not the same as a heart failure hospitalization, but some trials are now including these other heart failure events in their primary endpoint.
Scott D. Solomon, MD, professor of medicine at Harvard Medical School and director of noninvasive cardiology at Brigham and Women’s Hospital in Boston, made these comments as chair of the session where Dr. Aziz gave his report and in an interview. He has been a consultant to and/or received research support from Alnylam, Amgen, AstraZeneca, Bristol-Myers Squibb, Cytokinetics, GlaxoSmithKline, Ionis, Merck, Novartis, and Sanofi.
DALLAS – U.S. hospitals have recently shown a consistent and disturbing disconnect between reductions in their heart failure hospital readmission rates and heart failure mortality. Readmissions have dropped while mortality has risen.
“Despite reductions in 30-day heart failure readmissions in 89% of U.S. hospitals” during 2009-2016, “30-day heart failure mortality rates increased at 73%* of these ‘successful’ hospitals” during the same period,” Ahmad A. Abdul-Aziz, MD, said at the annual scientific meeting of the Heart Failure Society of America.
These shifts in the outcomes of U.S. patients hospitalized for acute heart failure episodes are tied to the penalties that the Centers for Medicare & Medicaid Services began slapping on hospitals in 2013 for excess 30-day readmissions for heart failure patients and in 2014 for excess mortality. A problem with these two CMS programs is that the penalty on inferior readmissions performance is a lot stiffer than for excess mortality, Dr. Aziz noted: a 0.2% penalty on payments for high mortality, compared with a 3% penalty for excess readmissions, a disparity that can make hospitals focus more on the readmissions side, he suggested.
Dr. Aziz’s report isn’t the first to make this observation. Study results published earlier in 2017 used CMS Medicare data from 2008 to 2014 to show that during that period, heart failure 30-day mortality rates following hospital discharge rose by 1.3%, while 30-day readmissions fell by 2.1% (JAMA. 2017 July 18;318[3]:270-8). On the basis of these numbers, as many as 5,200 additional deaths to U.S. heart failure patients in 2014 “may be related to the Hospital Readmission Reduction Program” of CMS, Gregg C. Fonarow, MD, said during a separate talk at the meeting.
The analysis reported by Dr. Aziz included data from 3,265 U.S. hospitals for heart failure patients, and data from 1,621 hospitals that managed patients with acute MIs, another disease that the CMS has targeted for penalties based on 30-day readmissions and 30-day postdischarge mortality rates. During the 8-year period studied, heart failure 30-day readmissions fell by 2.2% while 30-day mortality rose by 1%. In contrast, among acute MI patients, readmissions fell by 3% and mortality also fell, by 2.2%, Dr. Abdul-Aziz reported.
Dr. Abdul-Aziz had no disclosures. Dr. Fonarow had been a consultant to Amgen, Janssen, Medtronic, Novartis, St. Jude, and ZS Pharma.
[email protected]
On Twitter @mitchelzoler
*This article was updated October 5, 2017
DALLAS – U.S. hospitals have recently shown a consistent and disturbing disconnect between reductions in their heart failure hospital readmission rates and heart failure mortality. Readmissions have dropped while mortality has risen.
“Despite reductions in 30-day heart failure readmissions in 89% of U.S. hospitals” during 2009-2016, “30-day heart failure mortality rates increased at 73%* of these ‘successful’ hospitals” during the same period,” Ahmad A. Abdul-Aziz, MD, said at the annual scientific meeting of the Heart Failure Society of America.
These shifts in the outcomes of U.S. patients hospitalized for acute heart failure episodes are tied to the penalties that the Centers for Medicare & Medicaid Services began slapping on hospitals in 2013 for excess 30-day readmissions for heart failure patients and in 2014 for excess mortality. A problem with these two CMS programs is that the penalty on inferior readmissions performance is a lot stiffer than for excess mortality, Dr. Aziz noted: a 0.2% penalty on payments for high mortality, compared with a 3% penalty for excess readmissions, a disparity that can make hospitals focus more on the readmissions side, he suggested.
Dr. Aziz’s report isn’t the first to make this observation. Study results published earlier in 2017 used CMS Medicare data from 2008 to 2014 to show that during that period, heart failure 30-day mortality rates following hospital discharge rose by 1.3%, while 30-day readmissions fell by 2.1% (JAMA. 2017 July 18;318[3]:270-8). On the basis of these numbers, as many as 5,200 additional deaths to U.S. heart failure patients in 2014 “may be related to the Hospital Readmission Reduction Program” of CMS, Gregg C. Fonarow, MD, said during a separate talk at the meeting.
The analysis reported by Dr. Aziz included data from 3,265 U.S. hospitals for heart failure patients, and data from 1,621 hospitals that managed patients with acute MIs, another disease that the CMS has targeted for penalties based on 30-day readmissions and 30-day postdischarge mortality rates. During the 8-year period studied, heart failure 30-day readmissions fell by 2.2% while 30-day mortality rose by 1%. In contrast, among acute MI patients, readmissions fell by 3% and mortality also fell, by 2.2%, Dr. Abdul-Aziz reported.
Dr. Abdul-Aziz had no disclosures. Dr. Fonarow had been a consultant to Amgen, Janssen, Medtronic, Novartis, St. Jude, and ZS Pharma.
[email protected]
On Twitter @mitchelzoler
*This article was updated October 5, 2017
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: From 2009 to 2016, U.S. 30-day heart failure readmissions fell by 2.2% while 30-day heart failure mortality rose by 1%.
Data source: Review of Medicare data for 3,265 U.S. hospitals managing heart failure patients.
Disclosures: Dr. Abdul-Aziz had no disclosures. Dr. Fonarow had been a consultant to Amgen, Janssen, Medtronic, Novartis, St. Jude, and ZS Pharma.
Hepatitis C falls as barrier to heart transplantation
DALLAS – The heart transplant team at Vanderbilt University has successfully placed hearts from deceased, hepatitis C virus–positive patients into recipients, and then eradicated the subsequent infection that appeared in most recipients using a standard regimen.
So far, five of nine heart transplant recipients who developed a posttransplant hepatitis C virus (HCV) infection had the infection eradicated using one of the highly effective HCV drug regimens, and an additional three patients from the series are nearing their 12th week without detectable virus following treatment that marks a sustained response, Kelly H. Schlendorf, MD, said at the annual scientific meeting of the Heart Failure Society of America. The ninth patient died after developing a pulmonary embolism during the 7th week on antiviral therapy.
The recipients have been patients in a marginal clinical state and facing a long projected wait on the heart-recipient queue of the United Network for Organ Sharing (UNOS), Dr. Schlendorf said in an interview.
These have been “patients with a morbidity and mortality risk from waiting that can be mitigated by expanding the donor pool.” She gave an example of a patient with a left ventricular assist device that required replacement by either a second device or transplant, “so getting the transplant quickly was a good thing,” said Dr. Schlendorf, a cardiologist at Vanderbilt in Nashville.
Based on her analysis of UNOS data, “upwards of 100” and perhaps as many as 300 additional donor hearts could be available annually for U.S. transplants if the organs weren’t excluded because of HCV infection.
The Vanderbilt team has so far approached 15 patients in their program wait-listed for hearts about the possibility of accepting an HCV-positive organ, and all 15 have given their consent, she said. “We spend a lot of time talking with patients and their caregivers about the risks and benefits and possible complications.”
The 13 recipients, starting in September 2016, included 12 patients who were HCV naive and 1 patient with a history of HCV exposure. All 13 received the program’s standard three-drug regimen for immunosuppression.
During close surveillance, 9 of the 13 developed an infection. Patients with genotype 1 HCV received 12 weeks of treatment with ledipasvir plus sofosbuvir. Those infected with genotype 3 received 12-24 weeks of treatment with sofosbuvir plus velpatasvir. Treatment with these direct-acting antivirals meant that patients had to adjust the time when they took their proton-pump inhibitors, and they needed to stop treatment with diltiazem and statins while on the antivirals.
“In the era of direct-acting antivirals, HCV-positive donors may provide a safe and effective way to expand the donor pool and reduce wait-list times,” Dr. Schlendorf said. She noted that in recent years an increased number of potential organ donors have been HCV positive. She also cautioned that so far follow-up has been relatively brief, with no patient yet followed as long as 1 year after transplant.
The direct-acting HCV antivirals are expensive, and some payers established clinical criteria that patients must meet to qualify for coverage of these regimens. “We have not encountered difficulties getting insurers to pay,” Dr. Schlendorf said. Despite the antivirals’ cost there are significant cost savings from fewer days in the ICU waiting for heart transplantation and a reduced need for mechanical support as a bridge to transplant, she noted.
[email protected]
On Twitter @mitchelzoler
DALLAS – The heart transplant team at Vanderbilt University has successfully placed hearts from deceased, hepatitis C virus–positive patients into recipients, and then eradicated the subsequent infection that appeared in most recipients using a standard regimen.
So far, five of nine heart transplant recipients who developed a posttransplant hepatitis C virus (HCV) infection had the infection eradicated using one of the highly effective HCV drug regimens, and an additional three patients from the series are nearing their 12th week without detectable virus following treatment that marks a sustained response, Kelly H. Schlendorf, MD, said at the annual scientific meeting of the Heart Failure Society of America. The ninth patient died after developing a pulmonary embolism during the 7th week on antiviral therapy.
The recipients have been patients in a marginal clinical state and facing a long projected wait on the heart-recipient queue of the United Network for Organ Sharing (UNOS), Dr. Schlendorf said in an interview.
These have been “patients with a morbidity and mortality risk from waiting that can be mitigated by expanding the donor pool.” She gave an example of a patient with a left ventricular assist device that required replacement by either a second device or transplant, “so getting the transplant quickly was a good thing,” said Dr. Schlendorf, a cardiologist at Vanderbilt in Nashville.
Based on her analysis of UNOS data, “upwards of 100” and perhaps as many as 300 additional donor hearts could be available annually for U.S. transplants if the organs weren’t excluded because of HCV infection.
The Vanderbilt team has so far approached 15 patients in their program wait-listed for hearts about the possibility of accepting an HCV-positive organ, and all 15 have given their consent, she said. “We spend a lot of time talking with patients and their caregivers about the risks and benefits and possible complications.”
The 13 recipients, starting in September 2016, included 12 patients who were HCV naive and 1 patient with a history of HCV exposure. All 13 received the program’s standard three-drug regimen for immunosuppression.
During close surveillance, 9 of the 13 developed an infection. Patients with genotype 1 HCV received 12 weeks of treatment with ledipasvir plus sofosbuvir. Those infected with genotype 3 received 12-24 weeks of treatment with sofosbuvir plus velpatasvir. Treatment with these direct-acting antivirals meant that patients had to adjust the time when they took their proton-pump inhibitors, and they needed to stop treatment with diltiazem and statins while on the antivirals.
“In the era of direct-acting antivirals, HCV-positive donors may provide a safe and effective way to expand the donor pool and reduce wait-list times,” Dr. Schlendorf said. She noted that in recent years an increased number of potential organ donors have been HCV positive. She also cautioned that so far follow-up has been relatively brief, with no patient yet followed as long as 1 year after transplant.
The direct-acting HCV antivirals are expensive, and some payers established clinical criteria that patients must meet to qualify for coverage of these regimens. “We have not encountered difficulties getting insurers to pay,” Dr. Schlendorf said. Despite the antivirals’ cost there are significant cost savings from fewer days in the ICU waiting for heart transplantation and a reduced need for mechanical support as a bridge to transplant, she noted.
[email protected]
On Twitter @mitchelzoler
DALLAS – The heart transplant team at Vanderbilt University has successfully placed hearts from deceased, hepatitis C virus–positive patients into recipients, and then eradicated the subsequent infection that appeared in most recipients using a standard regimen.
So far, five of nine heart transplant recipients who developed a posttransplant hepatitis C virus (HCV) infection had the infection eradicated using one of the highly effective HCV drug regimens, and an additional three patients from the series are nearing their 12th week without detectable virus following treatment that marks a sustained response, Kelly H. Schlendorf, MD, said at the annual scientific meeting of the Heart Failure Society of America. The ninth patient died after developing a pulmonary embolism during the 7th week on antiviral therapy.
The recipients have been patients in a marginal clinical state and facing a long projected wait on the heart-recipient queue of the United Network for Organ Sharing (UNOS), Dr. Schlendorf said in an interview.
These have been “patients with a morbidity and mortality risk from waiting that can be mitigated by expanding the donor pool.” She gave an example of a patient with a left ventricular assist device that required replacement by either a second device or transplant, “so getting the transplant quickly was a good thing,” said Dr. Schlendorf, a cardiologist at Vanderbilt in Nashville.
Based on her analysis of UNOS data, “upwards of 100” and perhaps as many as 300 additional donor hearts could be available annually for U.S. transplants if the organs weren’t excluded because of HCV infection.
The Vanderbilt team has so far approached 15 patients in their program wait-listed for hearts about the possibility of accepting an HCV-positive organ, and all 15 have given their consent, she said. “We spend a lot of time talking with patients and their caregivers about the risks and benefits and possible complications.”
The 13 recipients, starting in September 2016, included 12 patients who were HCV naive and 1 patient with a history of HCV exposure. All 13 received the program’s standard three-drug regimen for immunosuppression.
During close surveillance, 9 of the 13 developed an infection. Patients with genotype 1 HCV received 12 weeks of treatment with ledipasvir plus sofosbuvir. Those infected with genotype 3 received 12-24 weeks of treatment with sofosbuvir plus velpatasvir. Treatment with these direct-acting antivirals meant that patients had to adjust the time when they took their proton-pump inhibitors, and they needed to stop treatment with diltiazem and statins while on the antivirals.
“In the era of direct-acting antivirals, HCV-positive donors may provide a safe and effective way to expand the donor pool and reduce wait-list times,” Dr. Schlendorf said. She noted that in recent years an increased number of potential organ donors have been HCV positive. She also cautioned that so far follow-up has been relatively brief, with no patient yet followed as long as 1 year after transplant.
The direct-acting HCV antivirals are expensive, and some payers established clinical criteria that patients must meet to qualify for coverage of these regimens. “We have not encountered difficulties getting insurers to pay,” Dr. Schlendorf said. Despite the antivirals’ cost there are significant cost savings from fewer days in the ICU waiting for heart transplantation and a reduced need for mechanical support as a bridge to transplant, she noted.
[email protected]
On Twitter @mitchelzoler
AT THE HFSA ANNUAL SCIENTIFIC MEETING
Key clinical point:
Major finding: Eight of nine patients who developed HCV infection had it eradicated by a direct-acting antiviral regimen.
Data source: A series of 13 patients treated at one U.S. center.
Disclosures: Dr. Schlendorf had no disclosures.