HFSA Annual Scientific Meeting

NATIONAL HARBOR, MD. – “There may be more to acute heart failure than meets the eye,” Hani N. Sabbah, Ph.D., said in a discussion during the annual meeting of the Heart Failure Society of America.

What remains unclear about acute decompensation episodes in patients with chronic heart failure is whether these events themselves exert a detrimental effect or if decompensation episodes merely flag patients in the worst clinical condition and are part of the natural history of worsening heart failure, said Dr. Sabbah, professor and director of cardiovascular research at Henry Ford Hospital in Detroit.

The importance of acute heart failure decompensations seems comparable to acute MIs, episodes in which incremental declines in heart-muscle function contribute to additional long-term worsening of heart failure, said Dr. Jay N. Cohn, another member of a discussion panel that also included Dr. Sidney Goldstein and Dr. Prakash Deedwania.

The risk from acute decompensations of heart failure highlights the importance of taking steps to cut the incidence of decompensations, said Dr. Cohn. Usual triggers of decompensation that could be targets for prevention are uncontrolled blood pressure and dietary indiscretions, Dr. Deedwania noted. Troponin leaks, a marker of myocardial-cell death, constitute another indicator of acute decompensation that may offer further insight into how to manage these episodes, he said.

Dr. Goldstein had no disclosures. Dr. Deedwania had no disclosures. Dr. Cohn receives royalties from Arbor Pharmaceuticals related to his work on hydralazine and isosorbide dinitrate. Dr. Sabbah is a consultant to Boston Scientific and an advisor to BioControl Medical and he has received research grants from both companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – “There may be more to acute heart failure than meets the eye,” Hani N. Sabbah, Ph.D., said in a discussion during the annual meeting of the Heart Failure Society of America.

What remains unclear about acute decompensation episodes in patients with chronic heart failure is whether these events themselves exert a detrimental effect or if decompensation episodes merely flag patients in the worst clinical condition and are part of the natural history of worsening heart failure, said Dr. Sabbah, professor and director of cardiovascular research at Henry Ford Hospital in Detroit.

The importance of acute heart failure decompensations seems comparable to acute MIs, episodes in which incremental declines in heart-muscle function contribute to additional long-term worsening of heart failure, said Dr. Jay N. Cohn, another member of a discussion panel that also included Dr. Sidney Goldstein and Dr. Prakash Deedwania.

The risk from acute decompensations of heart failure highlights the importance of taking steps to cut the incidence of decompensations, said Dr. Cohn. Usual triggers of decompensation that could be targets for prevention are uncontrolled blood pressure and dietary indiscretions, Dr. Deedwania noted. Troponin leaks, a marker of myocardial-cell death, constitute another indicator of acute decompensation that may offer further insight into how to manage these episodes, he said.

Dr. Goldstein had no disclosures. Dr. Deedwania had no disclosures. Dr. Cohn receives royalties from Arbor Pharmaceuticals related to his work on hydralazine and isosorbide dinitrate. Dr. Sabbah is a consultant to Boston Scientific and an advisor to BioControl Medical and he has received research grants from both companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – “There may be more to acute heart failure than meets the eye,” Hani N. Sabbah, Ph.D., said in a discussion during the annual meeting of the Heart Failure Society of America.

What remains unclear about acute decompensation episodes in patients with chronic heart failure is whether these events themselves exert a detrimental effect or if decompensation episodes merely flag patients in the worst clinical condition and are part of the natural history of worsening heart failure, said Dr. Sabbah, professor and director of cardiovascular research at Henry Ford Hospital in Detroit.

The importance of acute heart failure decompensations seems comparable to acute MIs, episodes in which incremental declines in heart-muscle function contribute to additional long-term worsening of heart failure, said Dr. Jay N. Cohn, another member of a discussion panel that also included Dr. Sidney Goldstein and Dr. Prakash Deedwania.

The risk from acute decompensations of heart failure highlights the importance of taking steps to cut the incidence of decompensations, said Dr. Cohn. Usual triggers of decompensation that could be targets for prevention are uncontrolled blood pressure and dietary indiscretions, Dr. Deedwania noted. Troponin leaks, a marker of myocardial-cell death, constitute another indicator of acute decompensation that may offer further insight into how to manage these episodes, he said.

Dr. Goldstein had no disclosures. Dr. Deedwania had no disclosures. Dr. Cohn receives royalties from Arbor Pharmaceuticals related to his work on hydralazine and isosorbide dinitrate. Dr. Sabbah is a consultant to Boston Scientific and an advisor to BioControl Medical and he has received research grants from both companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – Heart failure with preserved ejection fraction is a disease of premature aging of the myocardium and vasculature that is best managed by prevention, Dr. Jay N. Cohn said in a discussion during the annual meeting of the Heart Failure Society of America.

Heart failure with preserved ejection fraction (HFpEF) was misleadingly paired with heart failure with reduced ejection fraction because both share the symptoms of dyspnea and edema, although they differ in many other ways, added Dr. Cohen, professor of medicine at the University of Minnesota in Minneapolis.

Dr. Cohn said that he has recently prescribed a standard dosage of either an ACE inhibitor or angiotensin receptor–blocker drug to treat patients who have signs of a prematurely aged vasculature. The signs include reduced arterial compliance, thickened carotid walls, endothelial dysfunction, left ventricular hypertrophy, and elevated levels of brain natriuretic peptide. These drug classes offer potential for “vascular healing” at the prevention stage, said Dr. Cohn, who spoke in a group that also included Dr. Sidney Goldstein, Hani N. Sabbah, Ph.D., and Dr. Prakash Deedwania.

The best approach for preventing HFpEF is good management of blood pressure, obesity, and diabetes, said Dr. Sabbah. Good evidence also exists that aldosterone antagonists can reduce fibrosis, part of the pathology behind myocardial and vascular stiffening, he said.

Aldosterone antagonists have been underused for treating HFpEF and should be used more often, Dr. Cohn said.

Dr. Goldstein had no disclosures. Dr. Deedwania had no disclosures. Dr. Cohn receives royalties from Arbor Pharmaceuticals related to his work on hydralazine and isosorbide dinitrate. Dr. Sabbah is a consultant to Boston Scientific and an advisor to BioControl Medical and has received research grants from both companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – Heart failure with preserved ejection fraction is a disease of premature aging of the myocardium and vasculature that is best managed by prevention, Dr. Jay N. Cohn said in a discussion during the annual meeting of the Heart Failure Society of America.

Heart failure with preserved ejection fraction (HFpEF) was misleadingly paired with heart failure with reduced ejection fraction because both share the symptoms of dyspnea and edema, although they differ in many other ways, added Dr. Cohen, professor of medicine at the University of Minnesota in Minneapolis.

Dr. Cohn said that he has recently prescribed a standard dosage of either an ACE inhibitor or angiotensin receptor–blocker drug to treat patients who have signs of a prematurely aged vasculature. The signs include reduced arterial compliance, thickened carotid walls, endothelial dysfunction, left ventricular hypertrophy, and elevated levels of brain natriuretic peptide. These drug classes offer potential for “vascular healing” at the prevention stage, said Dr. Cohn, who spoke in a group that also included Dr. Sidney Goldstein, Hani N. Sabbah, Ph.D., and Dr. Prakash Deedwania.

The best approach for preventing HFpEF is good management of blood pressure, obesity, and diabetes, said Dr. Sabbah. Good evidence also exists that aldosterone antagonists can reduce fibrosis, part of the pathology behind myocardial and vascular stiffening, he said.

Aldosterone antagonists have been underused for treating HFpEF and should be used more often, Dr. Cohn said.

Dr. Goldstein had no disclosures. Dr. Deedwania had no disclosures. Dr. Cohn receives royalties from Arbor Pharmaceuticals related to his work on hydralazine and isosorbide dinitrate. Dr. Sabbah is a consultant to Boston Scientific and an advisor to BioControl Medical and has received research grants from both companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – Heart failure with preserved ejection fraction is a disease of premature aging of the myocardium and vasculature that is best managed by prevention, Dr. Jay N. Cohn said in a discussion during the annual meeting of the Heart Failure Society of America.

Heart failure with preserved ejection fraction (HFpEF) was misleadingly paired with heart failure with reduced ejection fraction because both share the symptoms of dyspnea and edema, although they differ in many other ways, added Dr. Cohen, professor of medicine at the University of Minnesota in Minneapolis.

Dr. Cohn said that he has recently prescribed a standard dosage of either an ACE inhibitor or angiotensin receptor–blocker drug to treat patients who have signs of a prematurely aged vasculature. The signs include reduced arterial compliance, thickened carotid walls, endothelial dysfunction, left ventricular hypertrophy, and elevated levels of brain natriuretic peptide. These drug classes offer potential for “vascular healing” at the prevention stage, said Dr. Cohn, who spoke in a group that also included Dr. Sidney Goldstein, Hani N. Sabbah, Ph.D., and Dr. Prakash Deedwania.

The best approach for preventing HFpEF is good management of blood pressure, obesity, and diabetes, said Dr. Sabbah. Good evidence also exists that aldosterone antagonists can reduce fibrosis, part of the pathology behind myocardial and vascular stiffening, he said.

Aldosterone antagonists have been underused for treating HFpEF and should be used more often, Dr. Cohn said.

Dr. Goldstein had no disclosures. Dr. Deedwania had no disclosures. Dr. Cohn receives royalties from Arbor Pharmaceuticals related to his work on hydralazine and isosorbide dinitrate. Dr. Sabbah is a consultant to Boston Scientific and an advisor to BioControl Medical and has received research grants from both companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – Acute decompensated heart failure is becoming more of an emergency.

Traditionally, it has been seen as a lumbering event that could be treated at a relatively leisurely pace, but heart failure physicians increasingly see the moment when patients arrive in the hospital with an episode of acute decompensated heart failure as a time-sensitive event that requires rapid intervention in a manner much more akin to an acute MI than to chronic heart failure.

While the tide is slowly shifting to put a premium on rapid treatment to try to decongest acute heart failure patients, the treatment options clinicians have available for these patients often remain inadequate.

“Development of drugs for acutely decompensated heart failure has been extremely difficult. We have done a really horrible job treating this disease,” Dr. Milton Packer said at the HFSA annual scientific meeting.

Treatment of acute heart failure patients has generally focused on relieving dyspnea, but part of the new appreciation of this state as an emergency event involves understanding that the pathology patients have when they reach the hospital is much more global and has profoundly morbid consequences.

“We want more from treatment than for patients to feel a little bit better an hour or two sooner” by relieving dyspnea, said Dr. Packer, professor of medicine and a heart failure specialist at the University of Texas Southwestern Medical Center in Dallas. “In the first 6 hours [of acute heart failure hospitalization], many patients are spilling troponin. We don’t know what this means, but the patients who spill troponin have a markedly increased risk for a more complicated hospital course.” About 10%-25% of patients hospitalized with acute heart failure have recurrent worsening heart failure, and many of these are also the patients who have a spike in their troponin level during initial hospitalization, he noted.

The troponin release in many patients and its association with worse outcomes is a clue that these patients are experiencing an ischemic myocardial event similar to an acute MI, possibly caused by myocardial-wall stretch, Dr. Packer said in an interview.

“If we can reduce this early acute cardiac dilatation, maybe we can reduce myocardial injury, reduce troponin release, and have favorable effects on clinically relevant events both short-term and long-term,” he said. “That’s why in trials [of investigational drugs for acute heart failure] we are treating patients earlier. Before we said we could enroll patients [into acute-treatment trials] within 48 hours of hospital admission. Now we enroll within 16 hours, or within 12 hours. We’ve learned that early intervention is important. That makes acute heart failure a lot more similar to an acute MI.”

European Society recommends faster acute heart failure management

European heart failure specialists have also become convinced that acute heart failure is an emergency that needs a rapid response. In June, the Heart Failure Association of the European Society of Cardiology published new recommendations on the in-hospital management of patients with acute heart failure (Eur J Heart Fail 2015 June;17[6];544-58). In the document, the association’s writing panel said, “The potentially greater benefit of early treatment is of conceptual importance in many cardiovascular presentations (e.g., myocardial infarction). Unfortunately, acute heart failure has not been considered with this regard until recently.” Breaking with the past, the association’s new recommendations now say that “all acute heart failure patients should receive appropriate therapy as early as possible,” an approach that involves starting acute management in the prehospital setting.

One member of the writing group for these recommendations put it more succinctly while speaking at the annual congress of the European Society of Cardiology in London in August: “Time is muscle in acute heart failure,” said Dr. Piotr Ponikowski, professor and heart failure specialist at the Medical University in Wroclaw, Poland. “When a patient has acute coronary syndrome everyone rushes, but we have patients with acute heart failure and no one rushes. We give furosemide, maybe something else, and then we wait and see.” He recommended adhering to a schedule that would have a patient assessed and initially treated within the first hour of hospitalization, and even sooner if treatment could start at the prehospital stage.

Like Dr. Packer, Dr. Ponikowski also lamented the inadequate tools now available for treating acute heart failure and the pressing need to identify better approaches to treatment, especially for selected acute heart failure patients.

“It is too simple to think that one drug or one treatment will help the entire spectrum of acute heart failure patients,” he said. “Our hypothesis is that profiling patients at every step of acute heart failure is crucial.”

He itemized five distinct types of acute heart failure patients based on their precipitating triggers of decompensation:

• Rapid arrhythmia or rhythm disturbance.

• Hypertension emergency.

• Pulmonary embolism.

• Pulmonary infection.

• Mechanical cause of acute heart failure.

“We need to clinically profile” patients into these subgroups to better tailor management, he said.

Another important aspect of patient heterogeneity is that fluid congestion may be less important in many patients compared with fluid redistribution from the splanchnic circulation. This distinction is important because fluid redistribution may be better treated with a vasodilator than with a diuretic, he noted. He voiced hope that two phase III trials now in progress with two unique vasodilator drugs, the TRUE-AHF trial of ularitide, and the RELAX-AHF-2 trial of serelaxin, may identify two new vasodilators with “unique effects” that could potentially launch a new era in management of selected patients with acute heart failure. Dr. Packer, the principal investigator for the ularitide trial, offered similar hope.

The responsiveness of acute heart failure patients to in-hospital treatment may vary depending on what end-organ damage they experience, Dr. Ponikowski said.

Mitchel L. Zoler/Frontline Medical News

This end-organ damage is often an acute process occurring during hospitalization caused by the fluid congestion and redistribution that occurs during acute heart failure, said Dr. Alexandre Mebazaa, professor of anesthesiology and critical care medicine at Lariboisière Hospital in Paris.

“Fluid overload leads to organ dysfunction. In the past, we thought that kidney dysfunction [occurring during acute heart failure] was due to low cardiac output, but we know that dysfunction in the kidney and liver is due to congestion, and diuretics do not remove water from the liver and kidney,” Dr. Mebazaa said in an interview. “Diuretics may remove fluid from vessels, but not from organs. We need new approaches to remove fluid from organs – from the kidney, liver, and lungs” – during acute heart failure. This is another reason why heart failure physicians are excited about the possibility of finding new vasodilators, such a ularitide and serelaxin, that might address the issue of venous congestion in peripheral organs.

Faster management endorsed by U.S. clinicians, too

“We used to think that the reason why patients with acute heart failure were not voiding well and became diuretic resistant was because of poor cardiac output. Now we know that there is a lot of venous congestion with an impact on the liver and kidneys,” agreed Dr. Mariell L. Jessup, professor and medical director of the Penn Heart and Vascular Center at the University of Pennsylvania in Philadelphia. “We’ve begun to appreciate how important venous congestion is in causing high pressures on the right side” of the circulatory system, she said in an interview.

Other U.S. physicians echo the call by Dr. Packer and the European cardiologists for faster treatment of acute heart failure. “I collected data at U.S. hospitals and found it took an average of 22 hours for decompensated heart failure patients to receive treatment,” said Dr. Maria Rosa Costanzo, medical director of the heart failure and pulmonary hypertension program at Advocate Heart Institute in Naperville, Ill. “I have tried to convey the message that these patients must be treated early, and this is associated with better outcomes,” she said in an interview during the HFSA meeting.

“Early treatment means at least two doses of intravenous diuretic in the emergency department. We’ve seen that the two immediate doses can make a big difference, producing shorter lengths of stay in the intensive care unit, fewer rehospitalizations, and fewer deaths,” according to data collected in the ADHERE (Acute Decompensated Heart Failure National Registry), she said. “But this has not yet been picked up in a lot of U.S. practice.” Although the hemodynamic abnormalities that lead up to an acute decompensation event can take several weeks of steady worsening before severe symptoms drive a patient to the hospital, once the patient requires hospitalization “it should be treated as an emergency,” she said.

Dr. Costanzo is a major advocate for using ultrafiltration as a second-line treatment for acute decompensated heart failure patients who do not adequately respond to diuretic treatment, but for the time being, ultrafiltration remains a controversial option that at least some other heart failure physicians do not endorse, and it can involve reimbursement issues as many insurers consider it investigational.

Mitchel L. Zoler/Frontline Medical News

“Try to get the patient decongested within the first 6 hours [after arrival at the hospital] or even sooner, within the first 1-2 hours,” recommended Dr. Christopher M. O’Connor, chief executive officer of Inova Heart and Vascular Institute in Falls Church, Va. He suggested treating patients with a combination of diuretics and vasodilators. “Some people are talking about instituting a performance measure for treating acute heart failure within the first 6 hours,” Dr. O’Connor said in an interview.

Currently, vasodilator treatment is limited to standard agents such as intravenous nitroglycerin, but Dr. O’Connor shared the hope that sometime soon a new vasodilator may be shown effective for acutely decompensated patients. He is a coinvestigator on the TRUE-AHF study of ularitide. “We hope that these new vasodilators, ularitide and serelaxin, will be good complements to diuretics, he said. Dr. O’Connor also recommended that clinicians shy away from using ultrafiltration as a back-up therapy, believing that it was shown ineffective and potentially harmful in results from the CARRESS-HF trial (N Engl J Med 2012 Dec 13;367[24]:2296-304).

But not all heart failure specialists see acute heart failure as a new frontier for early treatment and new drug discovery.

Mitchel L. Zoler/Frontline Medical News

“So much energy has already been spent on acute heart failure with very little return,” said Dr. Clyde W. Yancy, professor and chief of cardiology at Northwestern University in Chicago. “I think that our best opportunities in heart failure are in prevention and in better chronic care. The hospitalized patient is so broad and complex; if we’re looking at how to best spend our resources I think it’s best to focus on prevention,” he said in an interview.

“The hospital experience needs to shift toward better use of systems of care and focus less on the biology. The biggest challenge is how to coordinate all the systems to make sure that patients have access to the resources and can obtain [existing] medications. Patients don’t often have the literacy to understand discharge instructions, and our systems are overwhelmed by trying to have 7-day follow-up visits. Focusing on management of the hospitalized patient does not give us a good return on the investment. There is no question that acute heart failure is an unmet need, but the greater unmet need is prevention and improved chronic care. No single intervention will dramatically change the acute heart failure experience. Focusing on the hospitalization does not offer us management opportunities that are as robust as we once thought,” Dr. Yancy said.

Dr. Packer has been a consultant to 22 companies. Dr. Ponikowski has been a consultant to, speaker for, or has received research grants from 11 companies. Dr. Mebazaa has received speaking honoraria and consulting fees from 11 companies. Dr. Jessup, Dr. Costanzo, and Dr. Yancy had no disclosures. Dr. O’Connor has been a consultant to ResMed, Roche Diagnostics, Cardiorentis, Bayer, and Actelion and has received research grants from Otsuka, ResMed, and Roche Diagnostics.

mzoler@frontlinemedcom.com

On Twitter@mitchelzoler

NATIONAL HARBOR, MD. – Acute decompensated heart failure is becoming more of an emergency.

Traditionally, it has been seen as a lumbering event that could be treated at a relatively leisurely pace, but heart failure physicians increasingly see the moment when patients arrive in the hospital with an episode of acute decompensated heart failure as a time-sensitive event that requires rapid intervention in a manner much more akin to an acute MI than to chronic heart failure.

While the tide is slowly shifting to put a premium on rapid treatment to try to decongest acute heart failure patients, the treatment options clinicians have available for these patients often remain inadequate.

“Development of drugs for acutely decompensated heart failure has been extremely difficult. We have done a really horrible job treating this disease,” Dr. Milton Packer said at the HFSA annual scientific meeting.

Treatment of acute heart failure patients has generally focused on relieving dyspnea, but part of the new appreciation of this state as an emergency event involves understanding that the pathology patients have when they reach the hospital is much more global and has profoundly morbid consequences.

“We want more from treatment than for patients to feel a little bit better an hour or two sooner” by relieving dyspnea, said Dr. Packer, professor of medicine and a heart failure specialist at the University of Texas Southwestern Medical Center in Dallas. “In the first 6 hours [of acute heart failure hospitalization], many patients are spilling troponin. We don’t know what this means, but the patients who spill troponin have a markedly increased risk for a more complicated hospital course.” About 10%-25% of patients hospitalized with acute heart failure have recurrent worsening heart failure, and many of these are also the patients who have a spike in their troponin level during initial hospitalization, he noted.

The troponin release in many patients and its association with worse outcomes is a clue that these patients are experiencing an ischemic myocardial event similar to an acute MI, possibly caused by myocardial-wall stretch, Dr. Packer said in an interview.

“If we can reduce this early acute cardiac dilatation, maybe we can reduce myocardial injury, reduce troponin release, and have favorable effects on clinically relevant events both short-term and long-term,” he said. “That’s why in trials [of investigational drugs for acute heart failure] we are treating patients earlier. Before we said we could enroll patients [into acute-treatment trials] within 48 hours of hospital admission. Now we enroll within 16 hours, or within 12 hours. We’ve learned that early intervention is important. That makes acute heart failure a lot more similar to an acute MI.”

European Society recommends faster acute heart failure management

European heart failure specialists have also become convinced that acute heart failure is an emergency that needs a rapid response. In June, the Heart Failure Association of the European Society of Cardiology published new recommendations on the in-hospital management of patients with acute heart failure (Eur J Heart Fail 2015 June;17[6];544-58). In the document, the association’s writing panel said, “The potentially greater benefit of early treatment is of conceptual importance in many cardiovascular presentations (e.g., myocardial infarction). Unfortunately, acute heart failure has not been considered with this regard until recently.” Breaking with the past, the association’s new recommendations now say that “all acute heart failure patients should receive appropriate therapy as early as possible,” an approach that involves starting acute management in the prehospital setting.

One member of the writing group for these recommendations put it more succinctly while speaking at the annual congress of the European Society of Cardiology in London in August: “Time is muscle in acute heart failure,” said Dr. Piotr Ponikowski, professor and heart failure specialist at the Medical University in Wroclaw, Poland. “When a patient has acute coronary syndrome everyone rushes, but we have patients with acute heart failure and no one rushes. We give furosemide, maybe something else, and then we wait and see.” He recommended adhering to a schedule that would have a patient assessed and initially treated within the first hour of hospitalization, and even sooner if treatment could start at the prehospital stage.

Like Dr. Packer, Dr. Ponikowski also lamented the inadequate tools now available for treating acute heart failure and the pressing need to identify better approaches to treatment, especially for selected acute heart failure patients.

“It is too simple to think that one drug or one treatment will help the entire spectrum of acute heart failure patients,” he said. “Our hypothesis is that profiling patients at every step of acute heart failure is crucial.”

He itemized five distinct types of acute heart failure patients based on their precipitating triggers of decompensation:

• Rapid arrhythmia or rhythm disturbance.

• Hypertension emergency.

• Pulmonary embolism.

• Pulmonary infection.

• Mechanical cause of acute heart failure.

“We need to clinically profile” patients into these subgroups to better tailor management, he said.

Another important aspect of patient heterogeneity is that fluid congestion may be less important in many patients compared with fluid redistribution from the splanchnic circulation. This distinction is important because fluid redistribution may be better treated with a vasodilator than with a diuretic, he noted. He voiced hope that two phase III trials now in progress with two unique vasodilator drugs, the TRUE-AHF trial of ularitide, and the RELAX-AHF-2 trial of serelaxin, may identify two new vasodilators with “unique effects” that could potentially launch a new era in management of selected patients with acute heart failure. Dr. Packer, the principal investigator for the ularitide trial, offered similar hope.

The responsiveness of acute heart failure patients to in-hospital treatment may vary depending on what end-organ damage they experience, Dr. Ponikowski said.

Mitchel L. Zoler/Frontline Medical News

This end-organ damage is often an acute process occurring during hospitalization caused by the fluid congestion and redistribution that occurs during acute heart failure, said Dr. Alexandre Mebazaa, professor of anesthesiology and critical care medicine at Lariboisière Hospital in Paris.

“Fluid overload leads to organ dysfunction. In the past, we thought that kidney dysfunction [occurring during acute heart failure] was due to low cardiac output, but we know that dysfunction in the kidney and liver is due to congestion, and diuretics do not remove water from the liver and kidney,” Dr. Mebazaa said in an interview. “Diuretics may remove fluid from vessels, but not from organs. We need new approaches to remove fluid from organs – from the kidney, liver, and lungs” – during acute heart failure. This is another reason why heart failure physicians are excited about the possibility of finding new vasodilators, such a ularitide and serelaxin, that might address the issue of venous congestion in peripheral organs.

Faster management endorsed by U.S. clinicians, too

“We used to think that the reason why patients with acute heart failure were not voiding well and became diuretic resistant was because of poor cardiac output. Now we know that there is a lot of venous congestion with an impact on the liver and kidneys,” agreed Dr. Mariell L. Jessup, professor and medical director of the Penn Heart and Vascular Center at the University of Pennsylvania in Philadelphia. “We’ve begun to appreciate how important venous congestion is in causing high pressures on the right side” of the circulatory system, she said in an interview.

Other U.S. physicians echo the call by Dr. Packer and the European cardiologists for faster treatment of acute heart failure. “I collected data at U.S. hospitals and found it took an average of 22 hours for decompensated heart failure patients to receive treatment,” said Dr. Maria Rosa Costanzo, medical director of the heart failure and pulmonary hypertension program at Advocate Heart Institute in Naperville, Ill. “I have tried to convey the message that these patients must be treated early, and this is associated with better outcomes,” she said in an interview during the HFSA meeting.

“Early treatment means at least two doses of intravenous diuretic in the emergency department. We’ve seen that the two immediate doses can make a big difference, producing shorter lengths of stay in the intensive care unit, fewer rehospitalizations, and fewer deaths,” according to data collected in the ADHERE (Acute Decompensated Heart Failure National Registry), she said. “But this has not yet been picked up in a lot of U.S. practice.” Although the hemodynamic abnormalities that lead up to an acute decompensation event can take several weeks of steady worsening before severe symptoms drive a patient to the hospital, once the patient requires hospitalization “it should be treated as an emergency,” she said.

Dr. Costanzo is a major advocate for using ultrafiltration as a second-line treatment for acute decompensated heart failure patients who do not adequately respond to diuretic treatment, but for the time being, ultrafiltration remains a controversial option that at least some other heart failure physicians do not endorse, and it can involve reimbursement issues as many insurers consider it investigational.

Mitchel L. Zoler/Frontline Medical News

“Try to get the patient decongested within the first 6 hours [after arrival at the hospital] or even sooner, within the first 1-2 hours,” recommended Dr. Christopher M. O’Connor, chief executive officer of Inova Heart and Vascular Institute in Falls Church, Va. He suggested treating patients with a combination of diuretics and vasodilators. “Some people are talking about instituting a performance measure for treating acute heart failure within the first 6 hours,” Dr. O’Connor said in an interview.

Currently, vasodilator treatment is limited to standard agents such as intravenous nitroglycerin, but Dr. O’Connor shared the hope that sometime soon a new vasodilator may be shown effective for acutely decompensated patients. He is a coinvestigator on the TRUE-AHF study of ularitide. “We hope that these new vasodilators, ularitide and serelaxin, will be good complements to diuretics, he said. Dr. O’Connor also recommended that clinicians shy away from using ultrafiltration as a back-up therapy, believing that it was shown ineffective and potentially harmful in results from the CARRESS-HF trial (N Engl J Med 2012 Dec 13;367[24]:2296-304).

But not all heart failure specialists see acute heart failure as a new frontier for early treatment and new drug discovery.

Mitchel L. Zoler/Frontline Medical News

“So much energy has already been spent on acute heart failure with very little return,” said Dr. Clyde W. Yancy, professor and chief of cardiology at Northwestern University in Chicago. “I think that our best opportunities in heart failure are in prevention and in better chronic care. The hospitalized patient is so broad and complex; if we’re looking at how to best spend our resources I think it’s best to focus on prevention,” he said in an interview.

“The hospital experience needs to shift toward better use of systems of care and focus less on the biology. The biggest challenge is how to coordinate all the systems to make sure that patients have access to the resources and can obtain [existing] medications. Patients don’t often have the literacy to understand discharge instructions, and our systems are overwhelmed by trying to have 7-day follow-up visits. Focusing on management of the hospitalized patient does not give us a good return on the investment. There is no question that acute heart failure is an unmet need, but the greater unmet need is prevention and improved chronic care. No single intervention will dramatically change the acute heart failure experience. Focusing on the hospitalization does not offer us management opportunities that are as robust as we once thought,” Dr. Yancy said.

Dr. Packer has been a consultant to 22 companies. Dr. Ponikowski has been a consultant to, speaker for, or has received research grants from 11 companies. Dr. Mebazaa has received speaking honoraria and consulting fees from 11 companies. Dr. Jessup, Dr. Costanzo, and Dr. Yancy had no disclosures. Dr. O’Connor has been a consultant to ResMed, Roche Diagnostics, Cardiorentis, Bayer, and Actelion and has received research grants from Otsuka, ResMed, and Roche Diagnostics.

mzoler@frontlinemedcom.com

On Twitter@mitchelzoler

NATIONAL HARBOR, MD. – Acute decompensated heart failure is becoming more of an emergency.

Traditionally, it has been seen as a lumbering event that could be treated at a relatively leisurely pace, but heart failure physicians increasingly see the moment when patients arrive in the hospital with an episode of acute decompensated heart failure as a time-sensitive event that requires rapid intervention in a manner much more akin to an acute MI than to chronic heart failure.

While the tide is slowly shifting to put a premium on rapid treatment to try to decongest acute heart failure patients, the treatment options clinicians have available for these patients often remain inadequate.

“Development of drugs for acutely decompensated heart failure has been extremely difficult. We have done a really horrible job treating this disease,” Dr. Milton Packer said at the HFSA annual scientific meeting.

Treatment of acute heart failure patients has generally focused on relieving dyspnea, but part of the new appreciation of this state as an emergency event involves understanding that the pathology patients have when they reach the hospital is much more global and has profoundly morbid consequences.

“We want more from treatment than for patients to feel a little bit better an hour or two sooner” by relieving dyspnea, said Dr. Packer, professor of medicine and a heart failure specialist at the University of Texas Southwestern Medical Center in Dallas. “In the first 6 hours [of acute heart failure hospitalization], many patients are spilling troponin. We don’t know what this means, but the patients who spill troponin have a markedly increased risk for a more complicated hospital course.” About 10%-25% of patients hospitalized with acute heart failure have recurrent worsening heart failure, and many of these are also the patients who have a spike in their troponin level during initial hospitalization, he noted.

The troponin release in many patients and its association with worse outcomes is a clue that these patients are experiencing an ischemic myocardial event similar to an acute MI, possibly caused by myocardial-wall stretch, Dr. Packer said in an interview.

“If we can reduce this early acute cardiac dilatation, maybe we can reduce myocardial injury, reduce troponin release, and have favorable effects on clinically relevant events both short-term and long-term,” he said. “That’s why in trials [of investigational drugs for acute heart failure] we are treating patients earlier. Before we said we could enroll patients [into acute-treatment trials] within 48 hours of hospital admission. Now we enroll within 16 hours, or within 12 hours. We’ve learned that early intervention is important. That makes acute heart failure a lot more similar to an acute MI.”

European Society recommends faster acute heart failure management

European heart failure specialists have also become convinced that acute heart failure is an emergency that needs a rapid response. In June, the Heart Failure Association of the European Society of Cardiology published new recommendations on the in-hospital management of patients with acute heart failure (Eur J Heart Fail 2015 June;17[6];544-58). In the document, the association’s writing panel said, “The potentially greater benefit of early treatment is of conceptual importance in many cardiovascular presentations (e.g., myocardial infarction). Unfortunately, acute heart failure has not been considered with this regard until recently.” Breaking with the past, the association’s new recommendations now say that “all acute heart failure patients should receive appropriate therapy as early as possible,” an approach that involves starting acute management in the prehospital setting.

One member of the writing group for these recommendations put it more succinctly while speaking at the annual congress of the European Society of Cardiology in London in August: “Time is muscle in acute heart failure,” said Dr. Piotr Ponikowski, professor and heart failure specialist at the Medical University in Wroclaw, Poland. “When a patient has acute coronary syndrome everyone rushes, but we have patients with acute heart failure and no one rushes. We give furosemide, maybe something else, and then we wait and see.” He recommended adhering to a schedule that would have a patient assessed and initially treated within the first hour of hospitalization, and even sooner if treatment could start at the prehospital stage.

Like Dr. Packer, Dr. Ponikowski also lamented the inadequate tools now available for treating acute heart failure and the pressing need to identify better approaches to treatment, especially for selected acute heart failure patients.

“It is too simple to think that one drug or one treatment will help the entire spectrum of acute heart failure patients,” he said. “Our hypothesis is that profiling patients at every step of acute heart failure is crucial.”

He itemized five distinct types of acute heart failure patients based on their precipitating triggers of decompensation:

• Rapid arrhythmia or rhythm disturbance.

• Hypertension emergency.

• Pulmonary embolism.

• Pulmonary infection.

• Mechanical cause of acute heart failure.

“We need to clinically profile” patients into these subgroups to better tailor management, he said.

Another important aspect of patient heterogeneity is that fluid congestion may be less important in many patients compared with fluid redistribution from the splanchnic circulation. This distinction is important because fluid redistribution may be better treated with a vasodilator than with a diuretic, he noted. He voiced hope that two phase III trials now in progress with two unique vasodilator drugs, the TRUE-AHF trial of ularitide, and the RELAX-AHF-2 trial of serelaxin, may identify two new vasodilators with “unique effects” that could potentially launch a new era in management of selected patients with acute heart failure. Dr. Packer, the principal investigator for the ularitide trial, offered similar hope.

The responsiveness of acute heart failure patients to in-hospital treatment may vary depending on what end-organ damage they experience, Dr. Ponikowski said.

Mitchel L. Zoler/Frontline Medical News

This end-organ damage is often an acute process occurring during hospitalization caused by the fluid congestion and redistribution that occurs during acute heart failure, said Dr. Alexandre Mebazaa, professor of anesthesiology and critical care medicine at Lariboisière Hospital in Paris.

“Fluid overload leads to organ dysfunction. In the past, we thought that kidney dysfunction [occurring during acute heart failure] was due to low cardiac output, but we know that dysfunction in the kidney and liver is due to congestion, and diuretics do not remove water from the liver and kidney,” Dr. Mebazaa said in an interview. “Diuretics may remove fluid from vessels, but not from organs. We need new approaches to remove fluid from organs – from the kidney, liver, and lungs” – during acute heart failure. This is another reason why heart failure physicians are excited about the possibility of finding new vasodilators, such a ularitide and serelaxin, that might address the issue of venous congestion in peripheral organs.

Faster management endorsed by U.S. clinicians, too

“We used to think that the reason why patients with acute heart failure were not voiding well and became diuretic resistant was because of poor cardiac output. Now we know that there is a lot of venous congestion with an impact on the liver and kidneys,” agreed Dr. Mariell L. Jessup, professor and medical director of the Penn Heart and Vascular Center at the University of Pennsylvania in Philadelphia. “We’ve begun to appreciate how important venous congestion is in causing high pressures on the right side” of the circulatory system, she said in an interview.

Other U.S. physicians echo the call by Dr. Packer and the European cardiologists for faster treatment of acute heart failure. “I collected data at U.S. hospitals and found it took an average of 22 hours for decompensated heart failure patients to receive treatment,” said Dr. Maria Rosa Costanzo, medical director of the heart failure and pulmonary hypertension program at Advocate Heart Institute in Naperville, Ill. “I have tried to convey the message that these patients must be treated early, and this is associated with better outcomes,” she said in an interview during the HFSA meeting.

“Early treatment means at least two doses of intravenous diuretic in the emergency department. We’ve seen that the two immediate doses can make a big difference, producing shorter lengths of stay in the intensive care unit, fewer rehospitalizations, and fewer deaths,” according to data collected in the ADHERE (Acute Decompensated Heart Failure National Registry), she said. “But this has not yet been picked up in a lot of U.S. practice.” Although the hemodynamic abnormalities that lead up to an acute decompensation event can take several weeks of steady worsening before severe symptoms drive a patient to the hospital, once the patient requires hospitalization “it should be treated as an emergency,” she said.

Dr. Costanzo is a major advocate for using ultrafiltration as a second-line treatment for acute decompensated heart failure patients who do not adequately respond to diuretic treatment, but for the time being, ultrafiltration remains a controversial option that at least some other heart failure physicians do not endorse, and it can involve reimbursement issues as many insurers consider it investigational.

Mitchel L. Zoler/Frontline Medical News

“Try to get the patient decongested within the first 6 hours [after arrival at the hospital] or even sooner, within the first 1-2 hours,” recommended Dr. Christopher M. O’Connor, chief executive officer of Inova Heart and Vascular Institute in Falls Church, Va. He suggested treating patients with a combination of diuretics and vasodilators. “Some people are talking about instituting a performance measure for treating acute heart failure within the first 6 hours,” Dr. O’Connor said in an interview.

Currently, vasodilator treatment is limited to standard agents such as intravenous nitroglycerin, but Dr. O’Connor shared the hope that sometime soon a new vasodilator may be shown effective for acutely decompensated patients. He is a coinvestigator on the TRUE-AHF study of ularitide. “We hope that these new vasodilators, ularitide and serelaxin, will be good complements to diuretics, he said. Dr. O’Connor also recommended that clinicians shy away from using ultrafiltration as a back-up therapy, believing that it was shown ineffective and potentially harmful in results from the CARRESS-HF trial (N Engl J Med 2012 Dec 13;367[24]:2296-304).

But not all heart failure specialists see acute heart failure as a new frontier for early treatment and new drug discovery.

Mitchel L. Zoler/Frontline Medical News

“So much energy has already been spent on acute heart failure with very little return,” said Dr. Clyde W. Yancy, professor and chief of cardiology at Northwestern University in Chicago. “I think that our best opportunities in heart failure are in prevention and in better chronic care. The hospitalized patient is so broad and complex; if we’re looking at how to best spend our resources I think it’s best to focus on prevention,” he said in an interview.

“The hospital experience needs to shift toward better use of systems of care and focus less on the biology. The biggest challenge is how to coordinate all the systems to make sure that patients have access to the resources and can obtain [existing] medications. Patients don’t often have the literacy to understand discharge instructions, and our systems are overwhelmed by trying to have 7-day follow-up visits. Focusing on management of the hospitalized patient does not give us a good return on the investment. There is no question that acute heart failure is an unmet need, but the greater unmet need is prevention and improved chronic care. No single intervention will dramatically change the acute heart failure experience. Focusing on the hospitalization does not offer us management opportunities that are as robust as we once thought,” Dr. Yancy said.

Dr. Packer has been a consultant to 22 companies. Dr. Ponikowski has been a consultant to, speaker for, or has received research grants from 11 companies. Dr. Mebazaa has received speaking honoraria and consulting fees from 11 companies. Dr. Jessup, Dr. Costanzo, and Dr. Yancy had no disclosures. Dr. O’Connor has been a consultant to ResMed, Roche Diagnostics, Cardiorentis, Bayer, and Actelion and has received research grants from Otsuka, ResMed, and Roche Diagnostics.

mzoler@frontlinemedcom.com

On Twitter@mitchelzoler

NATIONAL HARBOR, MD. – The trial designed to definitively test the safety and efficacy of ultrafiltration as an alternative to intravenous diuretics for patients hospitalized with acute decompensated heart failure got cut to about a quarter of its planned enrollment by the company that recently acquired the ultrafiltration technology. This outcomes means that ultrafiltration’s role in acute heart failure remains uncertain and will stay that way for the foreseeable future.

As a consequence, ultrafiltration (also known as aquapheresis), approved for use in the United States by the Food and Drug Administration in 2002, will be used by believers in the treatment on some of the estimated 200,000 or more U.S. heart failure patients who become hospitalized each year with acute, severe congestion that is unresponsive to diuretic treatment. Other clinicians who remain skeptical of ultrafiltration’s safety and efficacy will not use it, and currently no prospect remains to resolve this uncertainty. Also limiting ultrafiltration’s use is its designation as investigational by U.S. health insurers.

“Early termination off the AVOID-HF [Aquapheresis Vs. Intravenous Diuretics and Hospitalization for Heart Failure] trial was a tragedy because it is unlikely we will ever see a trial of its size again,” commented Dr. G. Michael Felker during a discussion of treatment for acute heart failure at the at the annual meeting of the Heart Failure Society of America. “We still have no definitive answer” about ultrafiltration,” said Dr. Felker, professor of medicine and a cardiologist specializing in acute heart failure at Duke University in Durham, N.C.

Opinions about ultrafiltration and its role in treating patients with acute decompensated heart failure remain sharply split, although at this point, even proponents of the treatment concede that its use is limited to severely congested decompensated heart failure patients who prove unresponsive to intravenous diuretic therapy.

Mitchel L. Zoler/Frontline Medical News

Ultrafiltration is for patients with “recurrent decompensation (not the first episode) and a large amount of fluid overload (more than 10 pounds) who also have elevated central venous pressure and elevated abdominal pressure that reduces blood flow to the kidneys,” Dr. Maria Rosa Costanzo said in a video interview. Used in these patients at a low rate of 20-50 cc/hour to “gently remove fluid,” the treatment reduces central venous and intra-abdominal pressures, leading to increased urine output and restoration of diuretic sensitivity, said Dr. Costanzo, lead investigator for the AVOID-HF trial and medical director of the heart failure and pulmonary hypertension program at the Advocate Heart Institute in Naperville, Ill.

A dramatically opposing view of ultrafiltration came from Dr. Christopher M. O’Connor, a heart failure cardiologist and CEO of the Inova Heart and Vascular Institute in Falls Church, Va.

“Even in diuretic-resistant, patients I would not use ultrafiltration. It does not anymore fit into management” of acute decompensated heart failure patients, Dr. O’Connor said in an interview. The CARRESS-HF [Cardiorenal Rescue Study in Acute Decompensated Heart Failure] trial targeted patients with diuretic resistance, the very population we would need to treat, and we did not see an advantage to ultrafiltration,” said Dr. O’Connor, a coinvestigator on CARRESS-HF, an earlier trial that compared the two treatment methods (N Engl J Med. 2012 Dec 13;367[24]:2296-304).

“We need to understand who is the right patient” for ultrafiltration. “We need to continue to investigate [ultrafiltration] to know where it best fits,” commented Dr. Clyde W. Yancy, professor and chief of cardiology at Northwestern University in Chicago.


Mitchel L. Zoler/Frontline Medical News

AVOID-HF enrolled and randomized 224 patients with acute decompensated heart failure out of an anticipated enrollment of 810 patients. Analysis of the study’s primary endpoint, time to first heart failure event within the first 90 days following hospital discharge, occurred after an average of 34 days in 108 loop-diuretic treated patients and after an average 62 days in 105 ultrafiltration-treated patients, a difference that did not achieve statistical significance. A heart failure event within the first 90 days occurred in 25% of the ultrafiltration patients and in 35% of those on diuretic treatment, also a nonsignificant difference, Dr. Costanzo reported. Concurrent with her report at the meeting an article appeared online with the results (JACC Heart Fail. 2015;doi: 10.1016/j.jchf.2015.08.005).

Increases in serum creatinine were modest following ultrafiltration and similar to changes seen in the patients who received loop diuretic treatment. The biggest rise in average serum creatinine level occurred at 30 days after randomization, with an average 0.37 mg/dL rise among the ultrafiltration patients.

The abrupt shutdown in the AVOID-HF trial occurred following a change in ownership of the ultrafiltration technology used in the study. Ultrafiltration had been initially developed by CHF Solutions of Brooklyn Park, Minn. In 2010, Gambro, a Swedish company, acquired CHF Solutions and rights to the ultrafiltration system, and Gambro initiated the AVOID-HF trial. Baxter, in Deerfield, Ill., acquired Gambro in September 2013, and in April 2014, Baxter stopped the AVOID-HF trial because of slow projected enrollment, said Dr. Costanzo. But she strongly disagreed with this projection, and said that the trial showed no signs of futility or safety concerns when it came to a stop. Getting the data from Baxter to allow her and her associates to write their report and deliver their findings at the meeting took a lot of persuasion, Dr. Costanzo added.

Dr. Felker has been a consultant to and received research grants from 10 drug or device companies. He was a coinvestigator on the CARRESS-HF trial. Dr. Costanzo, lead investigator of AVOID-HF, said she had no relevant disclosures. Dr. O’Connor has been a consultant to ResMed, Roche Diagnostics, Cardiorentis, Bayer, and Actelion and has received research grants from Otsuka, ResMed, Roche Diagnostics. He was a coinvestigator on the CARESS-HF trial. Dr. Yancy had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – The trial designed to definitively test the safety and efficacy of ultrafiltration as an alternative to intravenous diuretics for patients hospitalized with acute decompensated heart failure got cut to about a quarter of its planned enrollment by the company that recently acquired the ultrafiltration technology. This outcomes means that ultrafiltration’s role in acute heart failure remains uncertain and will stay that way for the foreseeable future.

As a consequence, ultrafiltration (also known as aquapheresis), approved for use in the United States by the Food and Drug Administration in 2002, will be used by believers in the treatment on some of the estimated 200,000 or more U.S. heart failure patients who become hospitalized each year with acute, severe congestion that is unresponsive to diuretic treatment. Other clinicians who remain skeptical of ultrafiltration’s safety and efficacy will not use it, and currently no prospect remains to resolve this uncertainty. Also limiting ultrafiltration’s use is its designation as investigational by U.S. health insurers.

“Early termination off the AVOID-HF [Aquapheresis Vs. Intravenous Diuretics and Hospitalization for Heart Failure] trial was a tragedy because it is unlikely we will ever see a trial of its size again,” commented Dr. G. Michael Felker during a discussion of treatment for acute heart failure at the at the annual meeting of the Heart Failure Society of America. “We still have no definitive answer” about ultrafiltration,” said Dr. Felker, professor of medicine and a cardiologist specializing in acute heart failure at Duke University in Durham, N.C.

Opinions about ultrafiltration and its role in treating patients with acute decompensated heart failure remain sharply split, although at this point, even proponents of the treatment concede that its use is limited to severely congested decompensated heart failure patients who prove unresponsive to intravenous diuretic therapy.

Mitchel L. Zoler/Frontline Medical News

Ultrafiltration is for patients with “recurrent decompensation (not the first episode) and a large amount of fluid overload (more than 10 pounds) who also have elevated central venous pressure and elevated abdominal pressure that reduces blood flow to the kidneys,” Dr. Maria Rosa Costanzo said in a video interview. Used in these patients at a low rate of 20-50 cc/hour to “gently remove fluid,” the treatment reduces central venous and intra-abdominal pressures, leading to increased urine output and restoration of diuretic sensitivity, said Dr. Costanzo, lead investigator for the AVOID-HF trial and medical director of the heart failure and pulmonary hypertension program at the Advocate Heart Institute in Naperville, Ill.

A dramatically opposing view of ultrafiltration came from Dr. Christopher M. O’Connor, a heart failure cardiologist and CEO of the Inova Heart and Vascular Institute in Falls Church, Va.

“Even in diuretic-resistant, patients I would not use ultrafiltration. It does not anymore fit into management” of acute decompensated heart failure patients, Dr. O’Connor said in an interview. The CARRESS-HF [Cardiorenal Rescue Study in Acute Decompensated Heart Failure] trial targeted patients with diuretic resistance, the very population we would need to treat, and we did not see an advantage to ultrafiltration,” said Dr. O’Connor, a coinvestigator on CARRESS-HF, an earlier trial that compared the two treatment methods (N Engl J Med. 2012 Dec 13;367[24]:2296-304).

“We need to understand who is the right patient” for ultrafiltration. “We need to continue to investigate [ultrafiltration] to know where it best fits,” commented Dr. Clyde W. Yancy, professor and chief of cardiology at Northwestern University in Chicago.


Mitchel L. Zoler/Frontline Medical News

AVOID-HF enrolled and randomized 224 patients with acute decompensated heart failure out of an anticipated enrollment of 810 patients. Analysis of the study’s primary endpoint, time to first heart failure event within the first 90 days following hospital discharge, occurred after an average of 34 days in 108 loop-diuretic treated patients and after an average 62 days in 105 ultrafiltration-treated patients, a difference that did not achieve statistical significance. A heart failure event within the first 90 days occurred in 25% of the ultrafiltration patients and in 35% of those on diuretic treatment, also a nonsignificant difference, Dr. Costanzo reported. Concurrent with her report at the meeting an article appeared online with the results (JACC Heart Fail. 2015;doi: 10.1016/j.jchf.2015.08.005).

Increases in serum creatinine were modest following ultrafiltration and similar to changes seen in the patients who received loop diuretic treatment. The biggest rise in average serum creatinine level occurred at 30 days after randomization, with an average 0.37 mg/dL rise among the ultrafiltration patients.

The abrupt shutdown in the AVOID-HF trial occurred following a change in ownership of the ultrafiltration technology used in the study. Ultrafiltration had been initially developed by CHF Solutions of Brooklyn Park, Minn. In 2010, Gambro, a Swedish company, acquired CHF Solutions and rights to the ultrafiltration system, and Gambro initiated the AVOID-HF trial. Baxter, in Deerfield, Ill., acquired Gambro in September 2013, and in April 2014, Baxter stopped the AVOID-HF trial because of slow projected enrollment, said Dr. Costanzo. But she strongly disagreed with this projection, and said that the trial showed no signs of futility or safety concerns when it came to a stop. Getting the data from Baxter to allow her and her associates to write their report and deliver their findings at the meeting took a lot of persuasion, Dr. Costanzo added.

Dr. Felker has been a consultant to and received research grants from 10 drug or device companies. He was a coinvestigator on the CARRESS-HF trial. Dr. Costanzo, lead investigator of AVOID-HF, said she had no relevant disclosures. Dr. O’Connor has been a consultant to ResMed, Roche Diagnostics, Cardiorentis, Bayer, and Actelion and has received research grants from Otsuka, ResMed, Roche Diagnostics. He was a coinvestigator on the CARESS-HF trial. Dr. Yancy had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – The trial designed to definitively test the safety and efficacy of ultrafiltration as an alternative to intravenous diuretics for patients hospitalized with acute decompensated heart failure got cut to about a quarter of its planned enrollment by the company that recently acquired the ultrafiltration technology. This outcomes means that ultrafiltration’s role in acute heart failure remains uncertain and will stay that way for the foreseeable future.

As a consequence, ultrafiltration (also known as aquapheresis), approved for use in the United States by the Food and Drug Administration in 2002, will be used by believers in the treatment on some of the estimated 200,000 or more U.S. heart failure patients who become hospitalized each year with acute, severe congestion that is unresponsive to diuretic treatment. Other clinicians who remain skeptical of ultrafiltration’s safety and efficacy will not use it, and currently no prospect remains to resolve this uncertainty. Also limiting ultrafiltration’s use is its designation as investigational by U.S. health insurers.

“Early termination off the AVOID-HF [Aquapheresis Vs. Intravenous Diuretics and Hospitalization for Heart Failure] trial was a tragedy because it is unlikely we will ever see a trial of its size again,” commented Dr. G. Michael Felker during a discussion of treatment for acute heart failure at the at the annual meeting of the Heart Failure Society of America. “We still have no definitive answer” about ultrafiltration,” said Dr. Felker, professor of medicine and a cardiologist specializing in acute heart failure at Duke University in Durham, N.C.

Opinions about ultrafiltration and its role in treating patients with acute decompensated heart failure remain sharply split, although at this point, even proponents of the treatment concede that its use is limited to severely congested decompensated heart failure patients who prove unresponsive to intravenous diuretic therapy.

Mitchel L. Zoler/Frontline Medical News

Ultrafiltration is for patients with “recurrent decompensation (not the first episode) and a large amount of fluid overload (more than 10 pounds) who also have elevated central venous pressure and elevated abdominal pressure that reduces blood flow to the kidneys,” Dr. Maria Rosa Costanzo said in a video interview. Used in these patients at a low rate of 20-50 cc/hour to “gently remove fluid,” the treatment reduces central venous and intra-abdominal pressures, leading to increased urine output and restoration of diuretic sensitivity, said Dr. Costanzo, lead investigator for the AVOID-HF trial and medical director of the heart failure and pulmonary hypertension program at the Advocate Heart Institute in Naperville, Ill.

A dramatically opposing view of ultrafiltration came from Dr. Christopher M. O’Connor, a heart failure cardiologist and CEO of the Inova Heart and Vascular Institute in Falls Church, Va.

“Even in diuretic-resistant, patients I would not use ultrafiltration. It does not anymore fit into management” of acute decompensated heart failure patients, Dr. O’Connor said in an interview. The CARRESS-HF [Cardiorenal Rescue Study in Acute Decompensated Heart Failure] trial targeted patients with diuretic resistance, the very population we would need to treat, and we did not see an advantage to ultrafiltration,” said Dr. O’Connor, a coinvestigator on CARRESS-HF, an earlier trial that compared the two treatment methods (N Engl J Med. 2012 Dec 13;367[24]:2296-304).

“We need to understand who is the right patient” for ultrafiltration. “We need to continue to investigate [ultrafiltration] to know where it best fits,” commented Dr. Clyde W. Yancy, professor and chief of cardiology at Northwestern University in Chicago.


Mitchel L. Zoler/Frontline Medical News

AVOID-HF enrolled and randomized 224 patients with acute decompensated heart failure out of an anticipated enrollment of 810 patients. Analysis of the study’s primary endpoint, time to first heart failure event within the first 90 days following hospital discharge, occurred after an average of 34 days in 108 loop-diuretic treated patients and after an average 62 days in 105 ultrafiltration-treated patients, a difference that did not achieve statistical significance. A heart failure event within the first 90 days occurred in 25% of the ultrafiltration patients and in 35% of those on diuretic treatment, also a nonsignificant difference, Dr. Costanzo reported. Concurrent with her report at the meeting an article appeared online with the results (JACC Heart Fail. 2015;doi: 10.1016/j.jchf.2015.08.005).

Increases in serum creatinine were modest following ultrafiltration and similar to changes seen in the patients who received loop diuretic treatment. The biggest rise in average serum creatinine level occurred at 30 days after randomization, with an average 0.37 mg/dL rise among the ultrafiltration patients.

The abrupt shutdown in the AVOID-HF trial occurred following a change in ownership of the ultrafiltration technology used in the study. Ultrafiltration had been initially developed by CHF Solutions of Brooklyn Park, Minn. In 2010, Gambro, a Swedish company, acquired CHF Solutions and rights to the ultrafiltration system, and Gambro initiated the AVOID-HF trial. Baxter, in Deerfield, Ill., acquired Gambro in September 2013, and in April 2014, Baxter stopped the AVOID-HF trial because of slow projected enrollment, said Dr. Costanzo. But she strongly disagreed with this projection, and said that the trial showed no signs of futility or safety concerns when it came to a stop. Getting the data from Baxter to allow her and her associates to write their report and deliver their findings at the meeting took a lot of persuasion, Dr. Costanzo added.

Dr. Felker has been a consultant to and received research grants from 10 drug or device companies. He was a coinvestigator on the CARRESS-HF trial. Dr. Costanzo, lead investigator of AVOID-HF, said she had no relevant disclosures. Dr. O’Connor has been a consultant to ResMed, Roche Diagnostics, Cardiorentis, Bayer, and Actelion and has received research grants from Otsuka, ResMed, Roche Diagnostics. He was a coinvestigator on the CARESS-HF trial. Dr. Yancy had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Heart failure physicians were quick to embrace the sub–120 mm Hg systolic blood pressure target for both patients and at-risk people fewer than 3 weeks after the early-release news came out from the SPRINT trial that treating to this level produced a significant cut in cardiovascular disease events, compared with a less stringent systolic blood-pressure target of below 140 mm Hg.

At the annual meeting of the Heart Failure Society of America this week – one of the first cardiology gatherings held since the SPRINT announcement on Sept. 11 – at least 10 heart failure specialists offered their opinion at various times during the sessions on what the results have already meant for their practice. What was most striking was their unanimity in accepting this new blood pressure treatment target for heart failure patients and for people at increased risk for developing heart failure, and the rapidity at which they had come to their decision despite the absence so far of details about the trial’s results.

The unifying theme was that these physicians constituted a highly receptive audience for the SPRINT message, several of these specialists said in interviews. They appeared poised to pounce on a scientific rationale as soon as it became available to adopt a more aggressive blood pressure goal. It’s certainly no coincidence that most (if not all) these physicians now see uncontrolled hypertension as one of the top drivers of both heart failure onset and progression.

“We’ve all had some misgivings” about the systolic blood pressure targets set by the JNC 8 panel members last year of less than 150 mm Hg or less than 140 mm Hg (depending on age), and as a result of those misgivings, “I think people were ready to do a reverse and accept a new, lower target,” said Dr. Margaret M. Redfield, a heart failure specialist who was among those at the meeting who voiced endorsement for a new, sub–120 mm Hg target. “We don’t have the [SPRINT] data yet, but it’s very unusual for the NHLBI to release trial information ahead of time, so it must be very dramatic,” she added.

“The data and safety monitoring board had strict rules to govern early stopping,” said Dr. Clyde W. Yancy, a heart failure cardiologist and a member of the SPRINT data and safety monitoring panel. While careful not to prematurely provide any unreleased details of the SPRINT results, Dr. Yancy tried to frame what the September announcement meant in objective terms, while also rationalizing the quick uptake of the finding by so many of his colleagues.

“The decision to stop early must have been driven by some high level of evidence,” he told me, “You can infer a significant scientific rational” for a new target of less than 120 mm Hg “and you have to also surmise that there was no signal of harm.”

And, of course, some cardiologists had decided even before the SPRINT results came out in September that a lower target was better even without any evidence to back up that instinct.

“I love the 120s; a 140-mm Hg target has always been too high for me,” said Dr. Ileana L. Piña, a heart failure specialist at Montefiore Medical Center, Bronx, N.Y.

Another question, following so many endorsements of the 120-mm Hg goal, was whether these physicians believed people stood a good chance to reach this ambitious target.

“It’s a target; it’s not that everyone will get to it, but we need to apply the same rigor for blood pressure control as we use in heart failure clinics,” Dr. Redfield said. “We need to use a system” for patient support and monitoring and to promote adherence to treatment, “and keep pushing” patients to work toward their goal, she said.

Dr. Yancy predicted that a more aggressive blood pressure goal will help generate a stronger and more innovative infrastructure of drugs and monitoring tools to help patients get there.

“If a target blood pressure of 120/80 mm Hg gains credibility in guidelines, I think that industry will respond” with more combined drug formulations, new drugs, and innovative methods for easier blood pressure measurement, he said.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Heart failure physicians were quick to embrace the sub–120 mm Hg systolic blood pressure target for both patients and at-risk people fewer than 3 weeks after the early-release news came out from the SPRINT trial that treating to this level produced a significant cut in cardiovascular disease events, compared with a less stringent systolic blood-pressure target of below 140 mm Hg.

At the annual meeting of the Heart Failure Society of America this week – one of the first cardiology gatherings held since the SPRINT announcement on Sept. 11 – at least 10 heart failure specialists offered their opinion at various times during the sessions on what the results have already meant for their practice. What was most striking was their unanimity in accepting this new blood pressure treatment target for heart failure patients and for people at increased risk for developing heart failure, and the rapidity at which they had come to their decision despite the absence so far of details about the trial’s results.

The unifying theme was that these physicians constituted a highly receptive audience for the SPRINT message, several of these specialists said in interviews. They appeared poised to pounce on a scientific rationale as soon as it became available to adopt a more aggressive blood pressure goal. It’s certainly no coincidence that most (if not all) these physicians now see uncontrolled hypertension as one of the top drivers of both heart failure onset and progression.

“We’ve all had some misgivings” about the systolic blood pressure targets set by the JNC 8 panel members last year of less than 150 mm Hg or less than 140 mm Hg (depending on age), and as a result of those misgivings, “I think people were ready to do a reverse and accept a new, lower target,” said Dr. Margaret M. Redfield, a heart failure specialist who was among those at the meeting who voiced endorsement for a new, sub–120 mm Hg target. “We don’t have the [SPRINT] data yet, but it’s very unusual for the NHLBI to release trial information ahead of time, so it must be very dramatic,” she added.

“The data and safety monitoring board had strict rules to govern early stopping,” said Dr. Clyde W. Yancy, a heart failure cardiologist and a member of the SPRINT data and safety monitoring panel. While careful not to prematurely provide any unreleased details of the SPRINT results, Dr. Yancy tried to frame what the September announcement meant in objective terms, while also rationalizing the quick uptake of the finding by so many of his colleagues.

“The decision to stop early must have been driven by some high level of evidence,” he told me, “You can infer a significant scientific rational” for a new target of less than 120 mm Hg “and you have to also surmise that there was no signal of harm.”

And, of course, some cardiologists had decided even before the SPRINT results came out in September that a lower target was better even without any evidence to back up that instinct.

“I love the 120s; a 140-mm Hg target has always been too high for me,” said Dr. Ileana L. Piña, a heart failure specialist at Montefiore Medical Center, Bronx, N.Y.

Another question, following so many endorsements of the 120-mm Hg goal, was whether these physicians believed people stood a good chance to reach this ambitious target.

“It’s a target; it’s not that everyone will get to it, but we need to apply the same rigor for blood pressure control as we use in heart failure clinics,” Dr. Redfield said. “We need to use a system” for patient support and monitoring and to promote adherence to treatment, “and keep pushing” patients to work toward their goal, she said.

Dr. Yancy predicted that a more aggressive blood pressure goal will help generate a stronger and more innovative infrastructure of drugs and monitoring tools to help patients get there.

“If a target blood pressure of 120/80 mm Hg gains credibility in guidelines, I think that industry will respond” with more combined drug formulations, new drugs, and innovative methods for easier blood pressure measurement, he said.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Heart failure physicians were quick to embrace the sub–120 mm Hg systolic blood pressure target for both patients and at-risk people fewer than 3 weeks after the early-release news came out from the SPRINT trial that treating to this level produced a significant cut in cardiovascular disease events, compared with a less stringent systolic blood-pressure target of below 140 mm Hg.

At the annual meeting of the Heart Failure Society of America this week – one of the first cardiology gatherings held since the SPRINT announcement on Sept. 11 – at least 10 heart failure specialists offered their opinion at various times during the sessions on what the results have already meant for their practice. What was most striking was their unanimity in accepting this new blood pressure treatment target for heart failure patients and for people at increased risk for developing heart failure, and the rapidity at which they had come to their decision despite the absence so far of details about the trial’s results.

The unifying theme was that these physicians constituted a highly receptive audience for the SPRINT message, several of these specialists said in interviews. They appeared poised to pounce on a scientific rationale as soon as it became available to adopt a more aggressive blood pressure goal. It’s certainly no coincidence that most (if not all) these physicians now see uncontrolled hypertension as one of the top drivers of both heart failure onset and progression.

“We’ve all had some misgivings” about the systolic blood pressure targets set by the JNC 8 panel members last year of less than 150 mm Hg or less than 140 mm Hg (depending on age), and as a result of those misgivings, “I think people were ready to do a reverse and accept a new, lower target,” said Dr. Margaret M. Redfield, a heart failure specialist who was among those at the meeting who voiced endorsement for a new, sub–120 mm Hg target. “We don’t have the [SPRINT] data yet, but it’s very unusual for the NHLBI to release trial information ahead of time, so it must be very dramatic,” she added.

“The data and safety monitoring board had strict rules to govern early stopping,” said Dr. Clyde W. Yancy, a heart failure cardiologist and a member of the SPRINT data and safety monitoring panel. While careful not to prematurely provide any unreleased details of the SPRINT results, Dr. Yancy tried to frame what the September announcement meant in objective terms, while also rationalizing the quick uptake of the finding by so many of his colleagues.

“The decision to stop early must have been driven by some high level of evidence,” he told me, “You can infer a significant scientific rational” for a new target of less than 120 mm Hg “and you have to also surmise that there was no signal of harm.”

And, of course, some cardiologists had decided even before the SPRINT results came out in September that a lower target was better even without any evidence to back up that instinct.

“I love the 120s; a 140-mm Hg target has always been too high for me,” said Dr. Ileana L. Piña, a heart failure specialist at Montefiore Medical Center, Bronx, N.Y.

Another question, following so many endorsements of the 120-mm Hg goal, was whether these physicians believed people stood a good chance to reach this ambitious target.

“It’s a target; it’s not that everyone will get to it, but we need to apply the same rigor for blood pressure control as we use in heart failure clinics,” Dr. Redfield said. “We need to use a system” for patient support and monitoring and to promote adherence to treatment, “and keep pushing” patients to work toward their goal, she said.

Dr. Yancy predicted that a more aggressive blood pressure goal will help generate a stronger and more innovative infrastructure of drugs and monitoring tools to help patients get there.

“If a target blood pressure of 120/80 mm Hg gains credibility in guidelines, I think that industry will respond” with more combined drug formulations, new drugs, and innovative methods for easier blood pressure measurement, he said.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – In beta-blocker treatment of heart failure, dose matters; heart rate, not so much.

When using beta-blockers to treat patients with heart failure and reduced ejection fraction, administering a high, evidence-backed dosage of the drug had much more beneficial impact than did getting patients to a low heart rate, according to a post hoc analysis of data from more than 2,000 patients.

The finding provides new evidence supporting “titrating the beta-blocker to evidence-based, high dosages of a beta-blocker and not holding back,” Mona Fiuzat, Ph.D., said in an interview at the annual scientific meeting of the Heart Failure Society of America. “It’s not just lowering the heart rate; there is something else, other mechanisms [of beta-blocker effects] that may be of greater benefit” to patients beyond heart-rate reduction when patients they receive the full dosage of beta-blocker treatment that had been shown effective in the randomized trials run about 2 decades ago.

“The point of our report is that if you have [heart failure with reduced ejection fraction] patients on a beta-blocker, they will be better off by increasing the dose” to the target level rather than by adding an additional, non–beta-blocker drug, such as ivabradine (Corlanor), to further reduce heart rate, said Dr. Fiuzat, a clinical pharmacologist and heart-failure researcher at Duke University in Durham, N.C. In the trial that enrolled the 2,320 patients included in the current analysis, half the patients were not on their target beta-blocker dosage.

Some clinicians are too heart-rate focused, she said. “Our results show that there is added benefit from using the full beta-blocker dosage even when the patient’s heart rate is already low.”

The analysis run by Dr. Fiuzat and her associates used data collected in HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), a randomized, controlled study that assessed the impact of exercise training on patients with heart failure with reduced ejection fraction (JAMA 2009 Apr 8;301[14]:1439-50). All patients received usual care (and the intervention group also received exercise training), which meant they were on whichever beta-blocker and dosage their individual physician prescribed.

The current analysis converted these baseline dosages into carvedilol (Coreg) equivalents and identified the dosage levels as either low, defined as a daily carvedilol equivalent of less than 25 mg/day, or high, a daily equivalent of at least 25 mg/day. The analysis also categorized heart rate at baseline into a high rate defined as at least 70 beats/min, and a low rate of less than 70 beats/min. At entry, 71% of patients were on a high beta-blocker dosage (although in many cases not their full, ideal dosage), and 52% of patients had a high heart rate.

The new analysis showed that after a median follow-up of 2.5 years, the rate of all-cause death and all-cause hospitalization was significantly higher among patients who entered the study on a low beta-blocker dosage and with a high heart rate compared with patients in the other three groups: low dosage/low heart rate, high dosage/high heart rate, and high dosage/low heart rate. In addition, the results showed that a high beta-blocker dosage at baseline mitigated the impact of a high heart rate; patients in this subgroup had outcomes comparable to those of patients on a high beta-blocker dosage with a low heart rate.

In an analysis that adjusted for baseline differences in several clinical and demographic variables, patients on a high beta-blocker dosage had a statistically significant 13% reduced rate of all-cause death or all-cause hospitalization compared with patients on a low-dosage beta-blocker. In contrast, baseline heart rate had no statistically significant impact on outcomes, Dr. Fiuzat and her associates reported in an article published online concurrently with the presentation of the results at the meeting by one of Dr. Fiuzat’s colleagues (JACC: Heart Failure 2015. doi: 10.1016/j.jchf.2015.09.002]).

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – In beta-blocker treatment of heart failure, dose matters; heart rate, not so much.

When using beta-blockers to treat patients with heart failure and reduced ejection fraction, administering a high, evidence-backed dosage of the drug had much more beneficial impact than did getting patients to a low heart rate, according to a post hoc analysis of data from more than 2,000 patients.

The finding provides new evidence supporting “titrating the beta-blocker to evidence-based, high dosages of a beta-blocker and not holding back,” Mona Fiuzat, Ph.D., said in an interview at the annual scientific meeting of the Heart Failure Society of America. “It’s not just lowering the heart rate; there is something else, other mechanisms [of beta-blocker effects] that may be of greater benefit” to patients beyond heart-rate reduction when patients they receive the full dosage of beta-blocker treatment that had been shown effective in the randomized trials run about 2 decades ago.

“The point of our report is that if you have [heart failure with reduced ejection fraction] patients on a beta-blocker, they will be better off by increasing the dose” to the target level rather than by adding an additional, non–beta-blocker drug, such as ivabradine (Corlanor), to further reduce heart rate, said Dr. Fiuzat, a clinical pharmacologist and heart-failure researcher at Duke University in Durham, N.C. In the trial that enrolled the 2,320 patients included in the current analysis, half the patients were not on their target beta-blocker dosage.

Some clinicians are too heart-rate focused, she said. “Our results show that there is added benefit from using the full beta-blocker dosage even when the patient’s heart rate is already low.”

The analysis run by Dr. Fiuzat and her associates used data collected in HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), a randomized, controlled study that assessed the impact of exercise training on patients with heart failure with reduced ejection fraction (JAMA 2009 Apr 8;301[14]:1439-50). All patients received usual care (and the intervention group also received exercise training), which meant they were on whichever beta-blocker and dosage their individual physician prescribed.

The current analysis converted these baseline dosages into carvedilol (Coreg) equivalents and identified the dosage levels as either low, defined as a daily carvedilol equivalent of less than 25 mg/day, or high, a daily equivalent of at least 25 mg/day. The analysis also categorized heart rate at baseline into a high rate defined as at least 70 beats/min, and a low rate of less than 70 beats/min. At entry, 71% of patients were on a high beta-blocker dosage (although in many cases not their full, ideal dosage), and 52% of patients had a high heart rate.

The new analysis showed that after a median follow-up of 2.5 years, the rate of all-cause death and all-cause hospitalization was significantly higher among patients who entered the study on a low beta-blocker dosage and with a high heart rate compared with patients in the other three groups: low dosage/low heart rate, high dosage/high heart rate, and high dosage/low heart rate. In addition, the results showed that a high beta-blocker dosage at baseline mitigated the impact of a high heart rate; patients in this subgroup had outcomes comparable to those of patients on a high beta-blocker dosage with a low heart rate.

In an analysis that adjusted for baseline differences in several clinical and demographic variables, patients on a high beta-blocker dosage had a statistically significant 13% reduced rate of all-cause death or all-cause hospitalization compared with patients on a low-dosage beta-blocker. In contrast, baseline heart rate had no statistically significant impact on outcomes, Dr. Fiuzat and her associates reported in an article published online concurrently with the presentation of the results at the meeting by one of Dr. Fiuzat’s colleagues (JACC: Heart Failure 2015. doi: 10.1016/j.jchf.2015.09.002]).

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – In beta-blocker treatment of heart failure, dose matters; heart rate, not so much.

When using beta-blockers to treat patients with heart failure and reduced ejection fraction, administering a high, evidence-backed dosage of the drug had much more beneficial impact than did getting patients to a low heart rate, according to a post hoc analysis of data from more than 2,000 patients.

The finding provides new evidence supporting “titrating the beta-blocker to evidence-based, high dosages of a beta-blocker and not holding back,” Mona Fiuzat, Ph.D., said in an interview at the annual scientific meeting of the Heart Failure Society of America. “It’s not just lowering the heart rate; there is something else, other mechanisms [of beta-blocker effects] that may be of greater benefit” to patients beyond heart-rate reduction when patients they receive the full dosage of beta-blocker treatment that had been shown effective in the randomized trials run about 2 decades ago.

“The point of our report is that if you have [heart failure with reduced ejection fraction] patients on a beta-blocker, they will be better off by increasing the dose” to the target level rather than by adding an additional, non–beta-blocker drug, such as ivabradine (Corlanor), to further reduce heart rate, said Dr. Fiuzat, a clinical pharmacologist and heart-failure researcher at Duke University in Durham, N.C. In the trial that enrolled the 2,320 patients included in the current analysis, half the patients were not on their target beta-blocker dosage.

Some clinicians are too heart-rate focused, she said. “Our results show that there is added benefit from using the full beta-blocker dosage even when the patient’s heart rate is already low.”

The analysis run by Dr. Fiuzat and her associates used data collected in HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), a randomized, controlled study that assessed the impact of exercise training on patients with heart failure with reduced ejection fraction (JAMA 2009 Apr 8;301[14]:1439-50). All patients received usual care (and the intervention group also received exercise training), which meant they were on whichever beta-blocker and dosage their individual physician prescribed.

The current analysis converted these baseline dosages into carvedilol (Coreg) equivalents and identified the dosage levels as either low, defined as a daily carvedilol equivalent of less than 25 mg/day, or high, a daily equivalent of at least 25 mg/day. The analysis also categorized heart rate at baseline into a high rate defined as at least 70 beats/min, and a low rate of less than 70 beats/min. At entry, 71% of patients were on a high beta-blocker dosage (although in many cases not their full, ideal dosage), and 52% of patients had a high heart rate.

The new analysis showed that after a median follow-up of 2.5 years, the rate of all-cause death and all-cause hospitalization was significantly higher among patients who entered the study on a low beta-blocker dosage and with a high heart rate compared with patients in the other three groups: low dosage/low heart rate, high dosage/high heart rate, and high dosage/low heart rate. In addition, the results showed that a high beta-blocker dosage at baseline mitigated the impact of a high heart rate; patients in this subgroup had outcomes comparable to those of patients on a high beta-blocker dosage with a low heart rate.

In an analysis that adjusted for baseline differences in several clinical and demographic variables, patients on a high beta-blocker dosage had a statistically significant 13% reduced rate of all-cause death or all-cause hospitalization compared with patients on a low-dosage beta-blocker. In contrast, baseline heart rate had no statistically significant impact on outcomes, Dr. Fiuzat and her associates reported in an article published online concurrently with the presentation of the results at the meeting by one of Dr. Fiuzat’s colleagues (JACC: Heart Failure 2015. doi: 10.1016/j.jchf.2015.09.002]).

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – A next-generation left-ventricular assist device, the HeartMate 3, gave a solid debut performance in an uncontrolled series of the first 50 recipients, which was designed to gain the device CE mark approval in Europe.

In this study, run at 10 sites in Australia, Austria, Canada, Czech Republic, Germany, and Kazakhstan, the new-design left ventricular assist device (LVAD) numerically surpassed the study’s prespecified primary endpoint with 6-month recipient survival of 92%. This bested the target survival rate of 88% that the trial’s designers derived from the survival rate among 50 matched patients who had received a LVAD during 2012-2014 and had entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), Dr. Ivan Netuka said at the annual meeting of the Heart Failure Society of America.

Mitchel L. Zoler/Frontline Medical News

Other notable findings of the HeartMate 3’s performance in the first 50 patients followed for 6 months were no pump malfunctions, no thrombosis within the pump, and no evidence of hemolysis, said Dr. Netuka, deputy director of cardiovascular surgery at IKEM hospital in Prague.

HeartMate 3 features several improvements over the HeartMate II model, such as a fully magnetically levitated rotor designed to eliminate friction and wear within the pump. The device also is engineered to produce an artificial pulse of 30 beats per minute, and it can deliver a wide blood-flow range of 2-10 L/min. Larger and consistent pump gaps are designed to reduced shear stress on blood components.

The study enrolled patients during June-November 2014 with NYHA class IIIB or IV heart failure and stage D heart failure, with a left ventricular ejection fraction of 25% or less. The 50 patients averaged 59 years of age and 90% were men; they were divided about equally between patients who received the device as a bridge to transplant and those who received the LVAD as destination therapy.

During 6 months of follow-up, two patients received a heart transplant. Twenty-one (42%) of the enrolled patients classified as INTERMACS patient profile 3, 20 (40%) as profile 4, and 5 (10%) as profile 2 patients, with the remaining four patients falling into other profile levels. Twenty-one patients had concomitant heart surgery when they received their LVAD, usually valve replacement. All patients received warfarin treatment and aspirin following device placement. Dr. Netuka and his associates calculated an expected 6-month survival of 78% for the enrolled patients without LVAD intervention.

The four deaths included a patient who died from cardiac arrest following a stroke on day 19 – a complication judged attributable to the device-placement procedure, a patient with circulatory failure on day 48, a suicide on day 113, and a patient with multiorgan failure on day 144.

After 6 months of follow-up, notable adverse events included bleeding in 19 patients (38%) – including gastrointestinal bleeds in 4 patients (8%) – strokes in 6 patients (12%), and infections in 18 patients (36%). Most of the adverse events occurred in the first 7 days following LVAD placement. Three of the six strokes were judged procedure associated, Dr. Netuka said.

Following device placement, patients showed improvements in their NYHA class and quality of life; their 6-minute walk distance improved by an average of 231 m.

The HeartMate 3 device is currently undergoing U.S. assessment in comparison to HeartMate II prior to submission to the Food and Drug Administration. The randomized trial, known as MOMENTUM 3, plans to enroll 1,028 patients with completion scheduled for 2018.

The study was sponsored by Thoratec, which is developing the HeartMate 3 device. Dr. Netuka is a speaker for and consultant to Thoratec.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – A next-generation left-ventricular assist device, the HeartMate 3, gave a solid debut performance in an uncontrolled series of the first 50 recipients, which was designed to gain the device CE mark approval in Europe.

In this study, run at 10 sites in Australia, Austria, Canada, Czech Republic, Germany, and Kazakhstan, the new-design left ventricular assist device (LVAD) numerically surpassed the study’s prespecified primary endpoint with 6-month recipient survival of 92%. This bested the target survival rate of 88% that the trial’s designers derived from the survival rate among 50 matched patients who had received a LVAD during 2012-2014 and had entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), Dr. Ivan Netuka said at the annual meeting of the Heart Failure Society of America.

Mitchel L. Zoler/Frontline Medical News

Other notable findings of the HeartMate 3’s performance in the first 50 patients followed for 6 months were no pump malfunctions, no thrombosis within the pump, and no evidence of hemolysis, said Dr. Netuka, deputy director of cardiovascular surgery at IKEM hospital in Prague.

HeartMate 3 features several improvements over the HeartMate II model, such as a fully magnetically levitated rotor designed to eliminate friction and wear within the pump. The device also is engineered to produce an artificial pulse of 30 beats per minute, and it can deliver a wide blood-flow range of 2-10 L/min. Larger and consistent pump gaps are designed to reduced shear stress on blood components.

The study enrolled patients during June-November 2014 with NYHA class IIIB or IV heart failure and stage D heart failure, with a left ventricular ejection fraction of 25% or less. The 50 patients averaged 59 years of age and 90% were men; they were divided about equally between patients who received the device as a bridge to transplant and those who received the LVAD as destination therapy.

During 6 months of follow-up, two patients received a heart transplant. Twenty-one (42%) of the enrolled patients classified as INTERMACS patient profile 3, 20 (40%) as profile 4, and 5 (10%) as profile 2 patients, with the remaining four patients falling into other profile levels. Twenty-one patients had concomitant heart surgery when they received their LVAD, usually valve replacement. All patients received warfarin treatment and aspirin following device placement. Dr. Netuka and his associates calculated an expected 6-month survival of 78% for the enrolled patients without LVAD intervention.

The four deaths included a patient who died from cardiac arrest following a stroke on day 19 – a complication judged attributable to the device-placement procedure, a patient with circulatory failure on day 48, a suicide on day 113, and a patient with multiorgan failure on day 144.

After 6 months of follow-up, notable adverse events included bleeding in 19 patients (38%) – including gastrointestinal bleeds in 4 patients (8%) – strokes in 6 patients (12%), and infections in 18 patients (36%). Most of the adverse events occurred in the first 7 days following LVAD placement. Three of the six strokes were judged procedure associated, Dr. Netuka said.

Following device placement, patients showed improvements in their NYHA class and quality of life; their 6-minute walk distance improved by an average of 231 m.

The HeartMate 3 device is currently undergoing U.S. assessment in comparison to HeartMate II prior to submission to the Food and Drug Administration. The randomized trial, known as MOMENTUM 3, plans to enroll 1,028 patients with completion scheduled for 2018.

The study was sponsored by Thoratec, which is developing the HeartMate 3 device. Dr. Netuka is a speaker for and consultant to Thoratec.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

NATIONAL HARBOR, MD. – A next-generation left-ventricular assist device, the HeartMate 3, gave a solid debut performance in an uncontrolled series of the first 50 recipients, which was designed to gain the device CE mark approval in Europe.

In this study, run at 10 sites in Australia, Austria, Canada, Czech Republic, Germany, and Kazakhstan, the new-design left ventricular assist device (LVAD) numerically surpassed the study’s prespecified primary endpoint with 6-month recipient survival of 92%. This bested the target survival rate of 88% that the trial’s designers derived from the survival rate among 50 matched patients who had received a LVAD during 2012-2014 and had entered the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), Dr. Ivan Netuka said at the annual meeting of the Heart Failure Society of America.

Mitchel L. Zoler/Frontline Medical News

Other notable findings of the HeartMate 3’s performance in the first 50 patients followed for 6 months were no pump malfunctions, no thrombosis within the pump, and no evidence of hemolysis, said Dr. Netuka, deputy director of cardiovascular surgery at IKEM hospital in Prague.

HeartMate 3 features several improvements over the HeartMate II model, such as a fully magnetically levitated rotor designed to eliminate friction and wear within the pump. The device also is engineered to produce an artificial pulse of 30 beats per minute, and it can deliver a wide blood-flow range of 2-10 L/min. Larger and consistent pump gaps are designed to reduced shear stress on blood components.

The study enrolled patients during June-November 2014 with NYHA class IIIB or IV heart failure and stage D heart failure, with a left ventricular ejection fraction of 25% or less. The 50 patients averaged 59 years of age and 90% were men; they were divided about equally between patients who received the device as a bridge to transplant and those who received the LVAD as destination therapy.

During 6 months of follow-up, two patients received a heart transplant. Twenty-one (42%) of the enrolled patients classified as INTERMACS patient profile 3, 20 (40%) as profile 4, and 5 (10%) as profile 2 patients, with the remaining four patients falling into other profile levels. Twenty-one patients had concomitant heart surgery when they received their LVAD, usually valve replacement. All patients received warfarin treatment and aspirin following device placement. Dr. Netuka and his associates calculated an expected 6-month survival of 78% for the enrolled patients without LVAD intervention.

The four deaths included a patient who died from cardiac arrest following a stroke on day 19 – a complication judged attributable to the device-placement procedure, a patient with circulatory failure on day 48, a suicide on day 113, and a patient with multiorgan failure on day 144.

After 6 months of follow-up, notable adverse events included bleeding in 19 patients (38%) – including gastrointestinal bleeds in 4 patients (8%) – strokes in 6 patients (12%), and infections in 18 patients (36%). Most of the adverse events occurred in the first 7 days following LVAD placement. Three of the six strokes were judged procedure associated, Dr. Netuka said.

Following device placement, patients showed improvements in their NYHA class and quality of life; their 6-minute walk distance improved by an average of 231 m.

The HeartMate 3 device is currently undergoing U.S. assessment in comparison to HeartMate II prior to submission to the Food and Drug Administration. The randomized trial, known as MOMENTUM 3, plans to enroll 1,028 patients with completion scheduled for 2018.

The study was sponsored by Thoratec, which is developing the HeartMate 3 device. Dr. Netuka is a speaker for and consultant to Thoratec.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler