Heart Failure

LONDON – What was the top development in all of cardiology during the past year, the advance that holds the most far-reaching implications for clinical practice?

At the annual congress of the European Society of Cardiology, six experts each made a case for the biggest game changer in their discipline – risk prevention, electrophysiology, imaging, heart failure, percutaneous coronary intervention, and acute cardiac care. And when the audience of perhaps 400-strong had cast their votes, the winner was … the novel angiotensin receptor neprilysin inhibitor (ARNI) known as LCZ696 or valsartan/sacubitril. In the landmark PARADIGM-HF trial, the drug reduced the risk of cardiovascular death by 20% and heart failure hospitalization by 21% over and above what’s achieved with enalapril plus the other current guideline-recommended heart failure medications. “I’m a device person, but I’ve decided a device is not the most important recent innovation in heart failure,” Dr. Cecilia Linde said in her winning argument.

“This ARNI is the first new drug in years with a very clear impact on morbidity and mortality. This is why I believe PARADIGM-HF is the most important study result of the last year in heart failure. It will directly impact treatment and will change the ESC guidelines for heart failure therapy. The PARADIGM-HF results suggest that the ARNI should be given as first-line therapy instead of an ACE inhibitor or angiotensin receptor blocker,” said Dr. Linde, professor and head of cardiology at the Karolinska Institute, Stockholm.

In the double-blind, randomized 8,399-patient PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371[11]:993-1004), the number needed to treat with LCZ696 instead of enalapril for 27 months in order to avoid one cardiovascular death or heart failure hospitalization was 21. The number needed to treat to avoid one cardiovascular death was 32.

Electrophysiology

The big news here is the concept of the autonomic nervous system as the master controller of atrial fibrillation, governing both the firing of arrhythmic triggers and the change in the arrhythmogenic substrate over time, according to Dr. Sabine Ernst of the National Heart and Lung Institute at Imperial College, London.

“There is a new recognition of how the sympathetic and parasympathetic nervous systems interact to initiate and maintain arrhythmias. This will change the electrophysiology world forever,” she predicted.

Indeed, the future of antiarrhythmic therapy lies in neuromodulation of the autonomic nervous system, and it’s a lot closer than most cardiologists realize, according to the electrophysiologist.

She pointed to a recent study in which investigators at the University of Oklahoma Heart Rhythm Institute randomized 40 patients with paroxysmal atrial fibrillation to noninvasive low-level electrical stimulation of the vagus nerve or to sham treatment. The stimulation at 20 Hz suppressed atrial fibrillation and reduced levels of inflammatory cytokines (J Am Coll Cardiol. 2015 Mar 10;65[9]:867-75).

Vagus nerve stimulation was accomplished using a pair of clips attached to the external ear in order to access the tragus nerve. At just 20 Hz, participants felt no discomfort.

“This is just the very first step. It’s probably not the right frequency or intensity yet. But maybe – and I just want you to start to dream about this – just maybe this could be easily implanted in something we put in our ears. How nice it would be if we could add it to a hearing aid for a patient with atrial fibrillation; we would not need to bother with rate control anymore. Or to prevent atrial fibrillation, [we could put] a low-level vagus stimulator in the headphones for a smartphone,” Dr. Ernst said.

The noninvasiveness of this novel approach is what she finds most appealing.

“I want to stop putting catheters in other people’s hearts. I want to use a method I can ideally apply in the outpatient setting. I think we’ve got to move away from just destroying myocardium in patients with arrhythmias,” she said.

Cardiovascular prevention

Dr. Joep Perk nominated as the most important development of the past year in this field a new set of refined ECG screening criteria for asymptomatic hypertrophic cardiomyopathy (HCM) in athletes. Previous criteria – both the 2010 ESC criteria and the recently published Seattle criteria developed by an international collaborative group (Br J Sports Med. 2013 Feb;47[3]:122-4) – have unacceptably high false-positive rates, which lead to further testing, particularly in black athletes.

“In my personal experience, these young athletes start to think there is something wrong with their heart. They’ll be worried and might be erroneously disqualified. So even though we mean well, it does a lot of psychological harm,” said Dr. Perk, head of the department of internal medicine at Oskarshamn (Sweden) Hospital.

The so-called refined criteria (Circulation. 2014 Apr 22;129[16]:1637-49) were designed to improve upon the specificity of the ESC and Seattle criteria by excluding several isolated ECG patterns that have been shown not relevant in black athletes.

When the developers of the refined criteria applied all three sets of criteria to a large population of black and white athletes, including 103 young athletes with HCM, all three showed 98% sensitivity for the detection of HCM. However, the false-positive ECG rate in black athletes improved from 40.4% using the ESC criteria, to 18.4% with the Seattle criteria, to 11.5% using the refined criteria. Among white athletes, the false-positive rates using the three sets of criteria were 16.2%, 7.1%, and 5.3%.

“These new refined criteria should be incorporated into guidelines for the screening of athletes. They provide a 71% reduction in positive ECGs in black athletes, compared with the ESC recommendations,” Dr. Perk said.

Cardiac imaging

“I really think 3-D printing is going to revolutionize every aspect of medicine,” asserted Dr. Luigi Badano of the University of Padua (Italy).

At the ESC congress, his research group presented a study in which they used custom software to create an exact model of a real patient’s tricuspid valve out of liquid resin based on transthoracic echo images. It took 90 minutes.

Bruce Jancin/Frontline Medical News

“This technology allows us to hold the physical structure of the heart in our hands,” he noted. “We can use it to teach anatomy to medical students without a corpse, plan surgical interventions, and communicate with patients, showing them exact structures and revolutionizing the concept of informed consent.”

And that’s just scratching the surface. He noted that investigators at Wake Forest Baptist Medical Center Institute for Regenerative Medicine in North Carolina recently utilized 3-D printing with bio-ink and bio-paper to print 3-D beating cardiac cells clustered into “organoids.” It’s the first step toward creating a prototype beating heart.

“Can you dream about that? The donor heart shortage could in the future be solved by printing a beating heart for insertion into the patient. The investigators predict they’ll have a functional beating heart within 20 years,” Dr. Badano said.

Acute cardiac care

Dr. Maddalena Lettino and her fellow leaders of the European Acute Cardiac Care Association agreed that the breakthrough of the year in their field was validation of a novel 1-hour rule-in/rule-out algorithm using high-sensitivity cardiac troponin T to accelerate management of patients who present to the emergency department with chest pain. According to studies totaling more than 3,000 patients with more than 600 MIs in which the assay and algorithm were tested, roughly 75% of patients can safely and accurately have acute MI ruled out or ruled in within 1 hour.

Given that close to 10% of all emergency department visits are for chest pain, adoption of this algorithm will reduce ED overcrowding, speed physician workflow, save health care systems money, and spare patients and families the anxiety that comes with a delayed diagnosis, said Dr. Lettino, director of the clinical cardiology unit at Humanitas Research Hospital in Milan.

Coronary intervention

The 15%-20% of coronary stent recipients who are at high bleeding risk constitute “the forgotten patient population,” said Dr. Philippe Garot of the Paris South Cardiovascular Institute.

He noted that the key question of whether such patients can be managed safely with a mere 1-month course of dual antiplatelet therapy will finally be answered this fall with the release of the LEADERS FREE trial results. This large, randomized double-blind trial compares safety and efficacy outcomes in patients assigned to a bare metal stent or the novel drug-eluting BioFreedom stent.

Stay tuned, because LEADERS FREE could be a game changer in interventional cardiology, he said.

The six presenters indicated they had no relevant financial conflicts.

bjancin@frontlinemedcom.com

LONDON – What was the top development in all of cardiology during the past year, the advance that holds the most far-reaching implications for clinical practice?

At the annual congress of the European Society of Cardiology, six experts each made a case for the biggest game changer in their discipline – risk prevention, electrophysiology, imaging, heart failure, percutaneous coronary intervention, and acute cardiac care. And when the audience of perhaps 400-strong had cast their votes, the winner was … the novel angiotensin receptor neprilysin inhibitor (ARNI) known as LCZ696 or valsartan/sacubitril. In the landmark PARADIGM-HF trial, the drug reduced the risk of cardiovascular death by 20% and heart failure hospitalization by 21% over and above what’s achieved with enalapril plus the other current guideline-recommended heart failure medications. “I’m a device person, but I’ve decided a device is not the most important recent innovation in heart failure,” Dr. Cecilia Linde said in her winning argument.

“This ARNI is the first new drug in years with a very clear impact on morbidity and mortality. This is why I believe PARADIGM-HF is the most important study result of the last year in heart failure. It will directly impact treatment and will change the ESC guidelines for heart failure therapy. The PARADIGM-HF results suggest that the ARNI should be given as first-line therapy instead of an ACE inhibitor or angiotensin receptor blocker,” said Dr. Linde, professor and head of cardiology at the Karolinska Institute, Stockholm.

In the double-blind, randomized 8,399-patient PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371[11]:993-1004), the number needed to treat with LCZ696 instead of enalapril for 27 months in order to avoid one cardiovascular death or heart failure hospitalization was 21. The number needed to treat to avoid one cardiovascular death was 32.

Electrophysiology

The big news here is the concept of the autonomic nervous system as the master controller of atrial fibrillation, governing both the firing of arrhythmic triggers and the change in the arrhythmogenic substrate over time, according to Dr. Sabine Ernst of the National Heart and Lung Institute at Imperial College, London.

“There is a new recognition of how the sympathetic and parasympathetic nervous systems interact to initiate and maintain arrhythmias. This will change the electrophysiology world forever,” she predicted.

Indeed, the future of antiarrhythmic therapy lies in neuromodulation of the autonomic nervous system, and it’s a lot closer than most cardiologists realize, according to the electrophysiologist.

She pointed to a recent study in which investigators at the University of Oklahoma Heart Rhythm Institute randomized 40 patients with paroxysmal atrial fibrillation to noninvasive low-level electrical stimulation of the vagus nerve or to sham treatment. The stimulation at 20 Hz suppressed atrial fibrillation and reduced levels of inflammatory cytokines (J Am Coll Cardiol. 2015 Mar 10;65[9]:867-75).

Vagus nerve stimulation was accomplished using a pair of clips attached to the external ear in order to access the tragus nerve. At just 20 Hz, participants felt no discomfort.

“This is just the very first step. It’s probably not the right frequency or intensity yet. But maybe – and I just want you to start to dream about this – just maybe this could be easily implanted in something we put in our ears. How nice it would be if we could add it to a hearing aid for a patient with atrial fibrillation; we would not need to bother with rate control anymore. Or to prevent atrial fibrillation, [we could put] a low-level vagus stimulator in the headphones for a smartphone,” Dr. Ernst said.

The noninvasiveness of this novel approach is what she finds most appealing.

“I want to stop putting catheters in other people’s hearts. I want to use a method I can ideally apply in the outpatient setting. I think we’ve got to move away from just destroying myocardium in patients with arrhythmias,” she said.

Cardiovascular prevention

Dr. Joep Perk nominated as the most important development of the past year in this field a new set of refined ECG screening criteria for asymptomatic hypertrophic cardiomyopathy (HCM) in athletes. Previous criteria – both the 2010 ESC criteria and the recently published Seattle criteria developed by an international collaborative group (Br J Sports Med. 2013 Feb;47[3]:122-4) – have unacceptably high false-positive rates, which lead to further testing, particularly in black athletes.

“In my personal experience, these young athletes start to think there is something wrong with their heart. They’ll be worried and might be erroneously disqualified. So even though we mean well, it does a lot of psychological harm,” said Dr. Perk, head of the department of internal medicine at Oskarshamn (Sweden) Hospital.

The so-called refined criteria (Circulation. 2014 Apr 22;129[16]:1637-49) were designed to improve upon the specificity of the ESC and Seattle criteria by excluding several isolated ECG patterns that have been shown not relevant in black athletes.

When the developers of the refined criteria applied all three sets of criteria to a large population of black and white athletes, including 103 young athletes with HCM, all three showed 98% sensitivity for the detection of HCM. However, the false-positive ECG rate in black athletes improved from 40.4% using the ESC criteria, to 18.4% with the Seattle criteria, to 11.5% using the refined criteria. Among white athletes, the false-positive rates using the three sets of criteria were 16.2%, 7.1%, and 5.3%.

“These new refined criteria should be incorporated into guidelines for the screening of athletes. They provide a 71% reduction in positive ECGs in black athletes, compared with the ESC recommendations,” Dr. Perk said.

Cardiac imaging

“I really think 3-D printing is going to revolutionize every aspect of medicine,” asserted Dr. Luigi Badano of the University of Padua (Italy).

At the ESC congress, his research group presented a study in which they used custom software to create an exact model of a real patient’s tricuspid valve out of liquid resin based on transthoracic echo images. It took 90 minutes.

Bruce Jancin/Frontline Medical News

“This technology allows us to hold the physical structure of the heart in our hands,” he noted. “We can use it to teach anatomy to medical students without a corpse, plan surgical interventions, and communicate with patients, showing them exact structures and revolutionizing the concept of informed consent.”

And that’s just scratching the surface. He noted that investigators at Wake Forest Baptist Medical Center Institute for Regenerative Medicine in North Carolina recently utilized 3-D printing with bio-ink and bio-paper to print 3-D beating cardiac cells clustered into “organoids.” It’s the first step toward creating a prototype beating heart.

“Can you dream about that? The donor heart shortage could in the future be solved by printing a beating heart for insertion into the patient. The investigators predict they’ll have a functional beating heart within 20 years,” Dr. Badano said.

Acute cardiac care

Dr. Maddalena Lettino and her fellow leaders of the European Acute Cardiac Care Association agreed that the breakthrough of the year in their field was validation of a novel 1-hour rule-in/rule-out algorithm using high-sensitivity cardiac troponin T to accelerate management of patients who present to the emergency department with chest pain. According to studies totaling more than 3,000 patients with more than 600 MIs in which the assay and algorithm were tested, roughly 75% of patients can safely and accurately have acute MI ruled out or ruled in within 1 hour.

Given that close to 10% of all emergency department visits are for chest pain, adoption of this algorithm will reduce ED overcrowding, speed physician workflow, save health care systems money, and spare patients and families the anxiety that comes with a delayed diagnosis, said Dr. Lettino, director of the clinical cardiology unit at Humanitas Research Hospital in Milan.

Coronary intervention

The 15%-20% of coronary stent recipients who are at high bleeding risk constitute “the forgotten patient population,” said Dr. Philippe Garot of the Paris South Cardiovascular Institute.

He noted that the key question of whether such patients can be managed safely with a mere 1-month course of dual antiplatelet therapy will finally be answered this fall with the release of the LEADERS FREE trial results. This large, randomized double-blind trial compares safety and efficacy outcomes in patients assigned to a bare metal stent or the novel drug-eluting BioFreedom stent.

Stay tuned, because LEADERS FREE could be a game changer in interventional cardiology, he said.

The six presenters indicated they had no relevant financial conflicts.

bjancin@frontlinemedcom.com

LONDON – What was the top development in all of cardiology during the past year, the advance that holds the most far-reaching implications for clinical practice?

At the annual congress of the European Society of Cardiology, six experts each made a case for the biggest game changer in their discipline – risk prevention, electrophysiology, imaging, heart failure, percutaneous coronary intervention, and acute cardiac care. And when the audience of perhaps 400-strong had cast their votes, the winner was … the novel angiotensin receptor neprilysin inhibitor (ARNI) known as LCZ696 or valsartan/sacubitril. In the landmark PARADIGM-HF trial, the drug reduced the risk of cardiovascular death by 20% and heart failure hospitalization by 21% over and above what’s achieved with enalapril plus the other current guideline-recommended heart failure medications. “I’m a device person, but I’ve decided a device is not the most important recent innovation in heart failure,” Dr. Cecilia Linde said in her winning argument.

“This ARNI is the first new drug in years with a very clear impact on morbidity and mortality. This is why I believe PARADIGM-HF is the most important study result of the last year in heart failure. It will directly impact treatment and will change the ESC guidelines for heart failure therapy. The PARADIGM-HF results suggest that the ARNI should be given as first-line therapy instead of an ACE inhibitor or angiotensin receptor blocker,” said Dr. Linde, professor and head of cardiology at the Karolinska Institute, Stockholm.

In the double-blind, randomized 8,399-patient PARADIGM-HF trial (N Engl J Med. 2014 Sep 11;371[11]:993-1004), the number needed to treat with LCZ696 instead of enalapril for 27 months in order to avoid one cardiovascular death or heart failure hospitalization was 21. The number needed to treat to avoid one cardiovascular death was 32.

Electrophysiology

The big news here is the concept of the autonomic nervous system as the master controller of atrial fibrillation, governing both the firing of arrhythmic triggers and the change in the arrhythmogenic substrate over time, according to Dr. Sabine Ernst of the National Heart and Lung Institute at Imperial College, London.

“There is a new recognition of how the sympathetic and parasympathetic nervous systems interact to initiate and maintain arrhythmias. This will change the electrophysiology world forever,” she predicted.

Indeed, the future of antiarrhythmic therapy lies in neuromodulation of the autonomic nervous system, and it’s a lot closer than most cardiologists realize, according to the electrophysiologist.

She pointed to a recent study in which investigators at the University of Oklahoma Heart Rhythm Institute randomized 40 patients with paroxysmal atrial fibrillation to noninvasive low-level electrical stimulation of the vagus nerve or to sham treatment. The stimulation at 20 Hz suppressed atrial fibrillation and reduced levels of inflammatory cytokines (J Am Coll Cardiol. 2015 Mar 10;65[9]:867-75).

Vagus nerve stimulation was accomplished using a pair of clips attached to the external ear in order to access the tragus nerve. At just 20 Hz, participants felt no discomfort.

“This is just the very first step. It’s probably not the right frequency or intensity yet. But maybe – and I just want you to start to dream about this – just maybe this could be easily implanted in something we put in our ears. How nice it would be if we could add it to a hearing aid for a patient with atrial fibrillation; we would not need to bother with rate control anymore. Or to prevent atrial fibrillation, [we could put] a low-level vagus stimulator in the headphones for a smartphone,” Dr. Ernst said.

The noninvasiveness of this novel approach is what she finds most appealing.

“I want to stop putting catheters in other people’s hearts. I want to use a method I can ideally apply in the outpatient setting. I think we’ve got to move away from just destroying myocardium in patients with arrhythmias,” she said.

Cardiovascular prevention

Dr. Joep Perk nominated as the most important development of the past year in this field a new set of refined ECG screening criteria for asymptomatic hypertrophic cardiomyopathy (HCM) in athletes. Previous criteria – both the 2010 ESC criteria and the recently published Seattle criteria developed by an international collaborative group (Br J Sports Med. 2013 Feb;47[3]:122-4) – have unacceptably high false-positive rates, which lead to further testing, particularly in black athletes.

“In my personal experience, these young athletes start to think there is something wrong with their heart. They’ll be worried and might be erroneously disqualified. So even though we mean well, it does a lot of psychological harm,” said Dr. Perk, head of the department of internal medicine at Oskarshamn (Sweden) Hospital.

The so-called refined criteria (Circulation. 2014 Apr 22;129[16]:1637-49) were designed to improve upon the specificity of the ESC and Seattle criteria by excluding several isolated ECG patterns that have been shown not relevant in black athletes.

When the developers of the refined criteria applied all three sets of criteria to a large population of black and white athletes, including 103 young athletes with HCM, all three showed 98% sensitivity for the detection of HCM. However, the false-positive ECG rate in black athletes improved from 40.4% using the ESC criteria, to 18.4% with the Seattle criteria, to 11.5% using the refined criteria. Among white athletes, the false-positive rates using the three sets of criteria were 16.2%, 7.1%, and 5.3%.

“These new refined criteria should be incorporated into guidelines for the screening of athletes. They provide a 71% reduction in positive ECGs in black athletes, compared with the ESC recommendations,” Dr. Perk said.

Cardiac imaging

“I really think 3-D printing is going to revolutionize every aspect of medicine,” asserted Dr. Luigi Badano of the University of Padua (Italy).

At the ESC congress, his research group presented a study in which they used custom software to create an exact model of a real patient’s tricuspid valve out of liquid resin based on transthoracic echo images. It took 90 minutes.

Bruce Jancin/Frontline Medical News

“This technology allows us to hold the physical structure of the heart in our hands,” he noted. “We can use it to teach anatomy to medical students without a corpse, plan surgical interventions, and communicate with patients, showing them exact structures and revolutionizing the concept of informed consent.”

And that’s just scratching the surface. He noted that investigators at Wake Forest Baptist Medical Center Institute for Regenerative Medicine in North Carolina recently utilized 3-D printing with bio-ink and bio-paper to print 3-D beating cardiac cells clustered into “organoids.” It’s the first step toward creating a prototype beating heart.

“Can you dream about that? The donor heart shortage could in the future be solved by printing a beating heart for insertion into the patient. The investigators predict they’ll have a functional beating heart within 20 years,” Dr. Badano said.

Acute cardiac care

Dr. Maddalena Lettino and her fellow leaders of the European Acute Cardiac Care Association agreed that the breakthrough of the year in their field was validation of a novel 1-hour rule-in/rule-out algorithm using high-sensitivity cardiac troponin T to accelerate management of patients who present to the emergency department with chest pain. According to studies totaling more than 3,000 patients with more than 600 MIs in which the assay and algorithm were tested, roughly 75% of patients can safely and accurately have acute MI ruled out or ruled in within 1 hour.

Given that close to 10% of all emergency department visits are for chest pain, adoption of this algorithm will reduce ED overcrowding, speed physician workflow, save health care systems money, and spare patients and families the anxiety that comes with a delayed diagnosis, said Dr. Lettino, director of the clinical cardiology unit at Humanitas Research Hospital in Milan.

Coronary intervention

The 15%-20% of coronary stent recipients who are at high bleeding risk constitute “the forgotten patient population,” said Dr. Philippe Garot of the Paris South Cardiovascular Institute.

He noted that the key question of whether such patients can be managed safely with a mere 1-month course of dual antiplatelet therapy will finally be answered this fall with the release of the LEADERS FREE trial results. This large, randomized double-blind trial compares safety and efficacy outcomes in patients assigned to a bare metal stent or the novel drug-eluting BioFreedom stent.

Stay tuned, because LEADERS FREE could be a game changer in interventional cardiology, he said.

The six presenters indicated they had no relevant financial conflicts.

bjancin@frontlinemedcom.com

LONDON – Cancer itself has cardiotoxic effects independent of those caused by chemotherapy, Dr. Stephan von Haehling said at the annual congress of the European Society of Cardiology.

Evidence from both animal and human studies indicates that the malignancy itself may be exerting adverse cardiac effects even before chemotherapy provides an additional hit to the heart, according to Dr. von Haehling, who is a cardiologist at Charity Medical School, Berlin.

jancin

“In patients with advanced cancer, significant alterations exist in several markers of cardiovascular perturbation independent of high-dose chemotherapy. So it looks like the cancer is doing something that’s further worsened when chemotherapy starts,” he explained.

Dr. von Haehling and his coinvestigators first demonstrated this phenomenon in a rat model of liver cancer (Eur Heart J. 2014 Apr;35[14]:932-41). The tumor-bearing rats had the classic symptoms of cancer cachexia, including fatigue, impaired exercise capacity, loss of body weight, and dyspnea, as well as progressive wasting of left ventricular mass, even before exposure to chemotherapy. Strikingly, administration of the cardioselective beta-blocker bisoprolol and the aldosterone inhibitor spironolactone reduced left ventricular wasting, curbed cardiac dysfunction, improved a validated measure of rat quality of life, and significantly prolonged rat survival, compared with placebo.

Further exploration of these findings in clinical trials deserves to be a priority in light of the potential quality-of-life benefits for cancer patients, Dr. von Haehling observed.

He and his coworkers followed up the rat study with a prospective study of 50 patients with colorectal cancer, 51 with heart failure, and 51 healthy controls. Of the colorectal cancer patients, 24 underwent echocardiography and other cardiovascular function studies before they went on chemotherapy, while the other 26 did so after starting chemotherapy.

The colorectal cancer patients had a mildly elevated heart rate: an average of 73 beats per minute, compared with 65 bpm in controls and in heart failure patients on beta-blocker therapy. “This is something I see quite often. These patients usually have a mildly elevated heart rate in the range of 80-90 [bpms] or even slightly above,” he said.

Heart rate variability, exercise capacity as measured by treadmill VO₂ max testing, and left ventricular ejection fraction were significantly lower in cancer patients than controls, and lower still in the heart failure patients. More interesting were the differences between chemotherapy-naive and on-treatment colorectal cancer patients. Several major determinants of cardiovascular function were impaired in chemotherapy-naive cancer patients, compared with controls, and even more severely impaired in cancer patients on chemotherapy.

For more about current thinking regarding the prevention, monitoring, and treatment of cardiac side effects of anticancer therapies, Dr. von Haehling recommended the multidisciplinary clinical practice guidelines developed by the European Society for Medical Oncology (Ann Oncol. 2012 Oct;23 Suppl 7:vii155-66).

He reported having no financial conflicts regarding his cardio-oncology studies.

bjancin@frontlinemedcom.com

LONDON – Cancer itself has cardiotoxic effects independent of those caused by chemotherapy, Dr. Stephan von Haehling said at the annual congress of the European Society of Cardiology.

Evidence from both animal and human studies indicates that the malignancy itself may be exerting adverse cardiac effects even before chemotherapy provides an additional hit to the heart, according to Dr. von Haehling, who is a cardiologist at Charity Medical School, Berlin.

jancin

“In patients with advanced cancer, significant alterations exist in several markers of cardiovascular perturbation independent of high-dose chemotherapy. So it looks like the cancer is doing something that’s further worsened when chemotherapy starts,” he explained.

Dr. von Haehling and his coinvestigators first demonstrated this phenomenon in a rat model of liver cancer (Eur Heart J. 2014 Apr;35[14]:932-41). The tumor-bearing rats had the classic symptoms of cancer cachexia, including fatigue, impaired exercise capacity, loss of body weight, and dyspnea, as well as progressive wasting of left ventricular mass, even before exposure to chemotherapy. Strikingly, administration of the cardioselective beta-blocker bisoprolol and the aldosterone inhibitor spironolactone reduced left ventricular wasting, curbed cardiac dysfunction, improved a validated measure of rat quality of life, and significantly prolonged rat survival, compared with placebo.

Further exploration of these findings in clinical trials deserves to be a priority in light of the potential quality-of-life benefits for cancer patients, Dr. von Haehling observed.

He and his coworkers followed up the rat study with a prospective study of 50 patients with colorectal cancer, 51 with heart failure, and 51 healthy controls. Of the colorectal cancer patients, 24 underwent echocardiography and other cardiovascular function studies before they went on chemotherapy, while the other 26 did so after starting chemotherapy.

The colorectal cancer patients had a mildly elevated heart rate: an average of 73 beats per minute, compared with 65 bpm in controls and in heart failure patients on beta-blocker therapy. “This is something I see quite often. These patients usually have a mildly elevated heart rate in the range of 80-90 [bpms] or even slightly above,” he said.

Heart rate variability, exercise capacity as measured by treadmill VO₂ max testing, and left ventricular ejection fraction were significantly lower in cancer patients than controls, and lower still in the heart failure patients. More interesting were the differences between chemotherapy-naive and on-treatment colorectal cancer patients. Several major determinants of cardiovascular function were impaired in chemotherapy-naive cancer patients, compared with controls, and even more severely impaired in cancer patients on chemotherapy.

For more about current thinking regarding the prevention, monitoring, and treatment of cardiac side effects of anticancer therapies, Dr. von Haehling recommended the multidisciplinary clinical practice guidelines developed by the European Society for Medical Oncology (Ann Oncol. 2012 Oct;23 Suppl 7:vii155-66).

He reported having no financial conflicts regarding his cardio-oncology studies.

bjancin@frontlinemedcom.com

LONDON – Cancer itself has cardiotoxic effects independent of those caused by chemotherapy, Dr. Stephan von Haehling said at the annual congress of the European Society of Cardiology.

Evidence from both animal and human studies indicates that the malignancy itself may be exerting adverse cardiac effects even before chemotherapy provides an additional hit to the heart, according to Dr. von Haehling, who is a cardiologist at Charity Medical School, Berlin.

jancin

“In patients with advanced cancer, significant alterations exist in several markers of cardiovascular perturbation independent of high-dose chemotherapy. So it looks like the cancer is doing something that’s further worsened when chemotherapy starts,” he explained.

Dr. von Haehling and his coinvestigators first demonstrated this phenomenon in a rat model of liver cancer (Eur Heart J. 2014 Apr;35[14]:932-41). The tumor-bearing rats had the classic symptoms of cancer cachexia, including fatigue, impaired exercise capacity, loss of body weight, and dyspnea, as well as progressive wasting of left ventricular mass, even before exposure to chemotherapy. Strikingly, administration of the cardioselective beta-blocker bisoprolol and the aldosterone inhibitor spironolactone reduced left ventricular wasting, curbed cardiac dysfunction, improved a validated measure of rat quality of life, and significantly prolonged rat survival, compared with placebo.

Further exploration of these findings in clinical trials deserves to be a priority in light of the potential quality-of-life benefits for cancer patients, Dr. von Haehling observed.

He and his coworkers followed up the rat study with a prospective study of 50 patients with colorectal cancer, 51 with heart failure, and 51 healthy controls. Of the colorectal cancer patients, 24 underwent echocardiography and other cardiovascular function studies before they went on chemotherapy, while the other 26 did so after starting chemotherapy.

The colorectal cancer patients had a mildly elevated heart rate: an average of 73 beats per minute, compared with 65 bpm in controls and in heart failure patients on beta-blocker therapy. “This is something I see quite often. These patients usually have a mildly elevated heart rate in the range of 80-90 [bpms] or even slightly above,” he said.

Heart rate variability, exercise capacity as measured by treadmill VO₂ max testing, and left ventricular ejection fraction were significantly lower in cancer patients than controls, and lower still in the heart failure patients. More interesting were the differences between chemotherapy-naive and on-treatment colorectal cancer patients. Several major determinants of cardiovascular function were impaired in chemotherapy-naive cancer patients, compared with controls, and even more severely impaired in cancer patients on chemotherapy.

For more about current thinking regarding the prevention, monitoring, and treatment of cardiac side effects of anticancer therapies, Dr. von Haehling recommended the multidisciplinary clinical practice guidelines developed by the European Society for Medical Oncology (Ann Oncol. 2012 Oct;23 Suppl 7:vii155-66).

He reported having no financial conflicts regarding his cardio-oncology studies.

bjancin@frontlinemedcom.com

The Food and Drug Administration has approved the combined use of ambrisentan (Letairis) and tadalafil for the treatment of pulmonary arterial hypertension based on positive results from the AMBITION trial, according to Gilead Sciences.

In the trial, 605 PAH patients with World Health Organization functional class II or III symptoms were randomly assigned to receive either ambrisentan, tadalafil, or a combination of the two. One-month outcomes were significantly better in the combination group, with only 8% of patients needing to be hospitalized for worsening PAH, compared with 22% in the ambrisentan group and 15% in the tadalafil group (N Engl J Med. 2015 Aug 27. doi: 10.1056/NEJMoa1413687).

Improvement from baseline in 6-minute walk distance after 24 weeks was also higher in the combination group, where patients walked a median of 24 meters farther than did the ambrisentan group and 20 meters more than did the tadalafil group.

Side effects tended to be more common in the combination group than in either of the single-drug groups, with the most common side effect, peripheral edema, affecting 45% of the combination group, 38% of the ambrisentan group, and 28% of the tadalafil group. Other common side effects included headache, nasal congestion, cough, anemia, dyspepsia, and bronchitis.

“Patients receiving ambrisentan and tadalafil up front are less likely to experience disease progression or be hospitalized, and have more improvement in exercise ability than patients receiving either effective therapy alone. As such, this combination represents a new treatment strategy for patients living with this debilitating and life-threatening disease,” Dr. Ronald J. Ortiz, professor of medicine at the University of California, Los Angeles, and an AMBITION investigator, said in a statement.

Ambrisentan, an endothelin receptor antagonist, was approved in 2007 as monotherapy for PAH to improve exercise ability and delay clinical worsening. Tadalafil, a phosphodiesterase type 5 inhibitor, was approved in 2009 to improve exercise ability in PAH patients.

Find the full press release on the Gilead website.

lfranki@frontlinemedcom.com

The Food and Drug Administration has approved the combined use of ambrisentan (Letairis) and tadalafil for the treatment of pulmonary arterial hypertension based on positive results from the AMBITION trial, according to Gilead Sciences.

In the trial, 605 PAH patients with World Health Organization functional class II or III symptoms were randomly assigned to receive either ambrisentan, tadalafil, or a combination of the two. One-month outcomes were significantly better in the combination group, with only 8% of patients needing to be hospitalized for worsening PAH, compared with 22% in the ambrisentan group and 15% in the tadalafil group (N Engl J Med. 2015 Aug 27. doi: 10.1056/NEJMoa1413687).

Improvement from baseline in 6-minute walk distance after 24 weeks was also higher in the combination group, where patients walked a median of 24 meters farther than did the ambrisentan group and 20 meters more than did the tadalafil group.

Side effects tended to be more common in the combination group than in either of the single-drug groups, with the most common side effect, peripheral edema, affecting 45% of the combination group, 38% of the ambrisentan group, and 28% of the tadalafil group. Other common side effects included headache, nasal congestion, cough, anemia, dyspepsia, and bronchitis.

“Patients receiving ambrisentan and tadalafil up front are less likely to experience disease progression or be hospitalized, and have more improvement in exercise ability than patients receiving either effective therapy alone. As such, this combination represents a new treatment strategy for patients living with this debilitating and life-threatening disease,” Dr. Ronald J. Ortiz, professor of medicine at the University of California, Los Angeles, and an AMBITION investigator, said in a statement.

Ambrisentan, an endothelin receptor antagonist, was approved in 2007 as monotherapy for PAH to improve exercise ability and delay clinical worsening. Tadalafil, a phosphodiesterase type 5 inhibitor, was approved in 2009 to improve exercise ability in PAH patients.

Find the full press release on the Gilead website.

lfranki@frontlinemedcom.com

The Food and Drug Administration has approved the combined use of ambrisentan (Letairis) and tadalafil for the treatment of pulmonary arterial hypertension based on positive results from the AMBITION trial, according to Gilead Sciences.

In the trial, 605 PAH patients with World Health Organization functional class II or III symptoms were randomly assigned to receive either ambrisentan, tadalafil, or a combination of the two. One-month outcomes were significantly better in the combination group, with only 8% of patients needing to be hospitalized for worsening PAH, compared with 22% in the ambrisentan group and 15% in the tadalafil group (N Engl J Med. 2015 Aug 27. doi: 10.1056/NEJMoa1413687).

Improvement from baseline in 6-minute walk distance after 24 weeks was also higher in the combination group, where patients walked a median of 24 meters farther than did the ambrisentan group and 20 meters more than did the tadalafil group.

Side effects tended to be more common in the combination group than in either of the single-drug groups, with the most common side effect, peripheral edema, affecting 45% of the combination group, 38% of the ambrisentan group, and 28% of the tadalafil group. Other common side effects included headache, nasal congestion, cough, anemia, dyspepsia, and bronchitis.

“Patients receiving ambrisentan and tadalafil up front are less likely to experience disease progression or be hospitalized, and have more improvement in exercise ability than patients receiving either effective therapy alone. As such, this combination represents a new treatment strategy for patients living with this debilitating and life-threatening disease,” Dr. Ronald J. Ortiz, professor of medicine at the University of California, Los Angeles, and an AMBITION investigator, said in a statement.

Ambrisentan, an endothelin receptor antagonist, was approved in 2007 as monotherapy for PAH to improve exercise ability and delay clinical worsening. Tadalafil, a phosphodiesterase type 5 inhibitor, was approved in 2009 to improve exercise ability in PAH patients.

Find the full press release on the Gilead website.

lfranki@frontlinemedcom.com

Physical activity reduces heart failure risk, and the more exertion, the stronger the effect, according to a meta-analysis published online Oct. 5 in Circulation.

“Walking 30 minutes a day as recommended in the U.S. physical activity guidelines, may not be good enough – significantly more physical activity may be necessary to reduce the risk of heart failure,” Dr. Jarett D. Berry, senior author of the study, said in a press release.

© Steve Cole/iStockphoto.com

Although physical inactivity has been implicated as a contributing factor in cardiovascular disease and coronary heart disease, a comprehensive analysis of the literature on the relationship of physical activity and heart failure risk has not previously been conducted, said Dr. Berry of the University of Texas Southwest Medical School in Dallas, and his colleagues. They conducted a meta-analysis of prospective cohort studies on the relationship of physical activity and heart failure in participants 18 years or older. They presented results by category of physical activity, using a random effects model, and by quantity of metabolic equivalent (MET)-minimum per week.

Twelve cohort studies with 20,203 heart failure events and 370,460 study participants during an average follow-up of 13 years were included in the meta-analysis.

Heart failure risk was 30% lower in the highest category of physical activity versus the lowest level of physical activity in a pooled analysis of hazard ratios. That risk was also reduced by 22% and 15% in moderate and light categories of physical activity, compared with the lowest, respectively (Circulation. 2015 Oct 5. doi: 10.1161/circulationaha.115.015853). All differences were statistically significant.

Subgroup analysis showed similar correlations between high levels of physical activity and reduced heart failure risk even with different ages, sex, and geographic locations.

As measured quantitatively, participants who engaged in the minimal recommended level of physical activity (500 MET mins/week) had a 10% lower risk of heart failure, compared with no physical activity, a 19% lower risk with twice the recommended level of physical activity, and a 35% lower risk with four times the recommended level of physical activity), all statistically significant differences.

Dr. Berry continued in the press release, “If you look at the general population, we’ve had tremendous success in reducing coronary heart disease over the last 30 years. But heart failure rates have not declined enough. The findings from the present study suggest that higher levels of physical activity may help combat this growing burden of heart failure.”

The authors report no conflicts of interest. Dr. Berry received funding from the Dedman Family Scholar in Clinical Care endowment at the University of Texas Southwestern Medical Center from the American Heart Association prevention network.

Dr. Berry received funding from the Dedman Family Scholar in Clinical Care endowment at the University of Texas Southwestern Medical Center from the American Heart Association prevention network. The authors report no conflicts of interest.

Physical activity reduces heart failure risk, and the more exertion, the stronger the effect, according to a meta-analysis published online Oct. 5 in Circulation.

“Walking 30 minutes a day as recommended in the U.S. physical activity guidelines, may not be good enough – significantly more physical activity may be necessary to reduce the risk of heart failure,” Dr. Jarett D. Berry, senior author of the study, said in a press release.

© Steve Cole/iStockphoto.com

Although physical inactivity has been implicated as a contributing factor in cardiovascular disease and coronary heart disease, a comprehensive analysis of the literature on the relationship of physical activity and heart failure risk has not previously been conducted, said Dr. Berry of the University of Texas Southwest Medical School in Dallas, and his colleagues. They conducted a meta-analysis of prospective cohort studies on the relationship of physical activity and heart failure in participants 18 years or older. They presented results by category of physical activity, using a random effects model, and by quantity of metabolic equivalent (MET)-minimum per week.

Twelve cohort studies with 20,203 heart failure events and 370,460 study participants during an average follow-up of 13 years were included in the meta-analysis.

Heart failure risk was 30% lower in the highest category of physical activity versus the lowest level of physical activity in a pooled analysis of hazard ratios. That risk was also reduced by 22% and 15% in moderate and light categories of physical activity, compared with the lowest, respectively (Circulation. 2015 Oct 5. doi: 10.1161/circulationaha.115.015853). All differences were statistically significant.

Subgroup analysis showed similar correlations between high levels of physical activity and reduced heart failure risk even with different ages, sex, and geographic locations.

As measured quantitatively, participants who engaged in the minimal recommended level of physical activity (500 MET mins/week) had a 10% lower risk of heart failure, compared with no physical activity, a 19% lower risk with twice the recommended level of physical activity, and a 35% lower risk with four times the recommended level of physical activity), all statistically significant differences.

Dr. Berry continued in the press release, “If you look at the general population, we’ve had tremendous success in reducing coronary heart disease over the last 30 years. But heart failure rates have not declined enough. The findings from the present study suggest that higher levels of physical activity may help combat this growing burden of heart failure.”

The authors report no conflicts of interest. Dr. Berry received funding from the Dedman Family Scholar in Clinical Care endowment at the University of Texas Southwestern Medical Center from the American Heart Association prevention network.

Dr. Berry received funding from the Dedman Family Scholar in Clinical Care endowment at the University of Texas Southwestern Medical Center from the American Heart Association prevention network. The authors report no conflicts of interest.

Physical activity reduces heart failure risk, and the more exertion, the stronger the effect, according to a meta-analysis published online Oct. 5 in Circulation.

“Walking 30 minutes a day as recommended in the U.S. physical activity guidelines, may not be good enough – significantly more physical activity may be necessary to reduce the risk of heart failure,” Dr. Jarett D. Berry, senior author of the study, said in a press release.

© Steve Cole/iStockphoto.com

Although physical inactivity has been implicated as a contributing factor in cardiovascular disease and coronary heart disease, a comprehensive analysis of the literature on the relationship of physical activity and heart failure risk has not previously been conducted, said Dr. Berry of the University of Texas Southwest Medical School in Dallas, and his colleagues. They conducted a meta-analysis of prospective cohort studies on the relationship of physical activity and heart failure in participants 18 years or older. They presented results by category of physical activity, using a random effects model, and by quantity of metabolic equivalent (MET)-minimum per week.

Twelve cohort studies with 20,203 heart failure events and 370,460 study participants during an average follow-up of 13 years were included in the meta-analysis.

Heart failure risk was 30% lower in the highest category of physical activity versus the lowest level of physical activity in a pooled analysis of hazard ratios. That risk was also reduced by 22% and 15% in moderate and light categories of physical activity, compared with the lowest, respectively (Circulation. 2015 Oct 5. doi: 10.1161/circulationaha.115.015853). All differences were statistically significant.

Subgroup analysis showed similar correlations between high levels of physical activity and reduced heart failure risk even with different ages, sex, and geographic locations.

As measured quantitatively, participants who engaged in the minimal recommended level of physical activity (500 MET mins/week) had a 10% lower risk of heart failure, compared with no physical activity, a 19% lower risk with twice the recommended level of physical activity, and a 35% lower risk with four times the recommended level of physical activity), all statistically significant differences.

Dr. Berry continued in the press release, “If you look at the general population, we’ve had tremendous success in reducing coronary heart disease over the last 30 years. But heart failure rates have not declined enough. The findings from the present study suggest that higher levels of physical activity may help combat this growing burden of heart failure.”

The authors report no conflicts of interest. Dr. Berry received funding from the Dedman Family Scholar in Clinical Care endowment at the University of Texas Southwestern Medical Center from the American Heart Association prevention network.

Dr. Berry received funding from the Dedman Family Scholar in Clinical Care endowment at the University of Texas Southwestern Medical Center from the American Heart Association prevention network. The authors report no conflicts of interest.

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

LONDON – Persistent mechanical dyssynchrony in patients with heart failure with reduced ejection fraction and a narrow QRS width appears to be a new marker of heightened risk.

That’s the key take-away message of an update of the EchoCRT trial presented by Dr. John Gorcsan III at the annual congress of the European Society of Cardiology.

EchoCRT was a large, multicenter randomized trial of cardiac resynchronization therapy (CRT) in patients with severely symptomatic heart failure with a QRS width of less than 130 ms, a left ventricular ejection fraction of 35% or less, and echocardiographic evidence of dyssynchrony. It was a negative study, with no improvement in rates of death or heart failure hospitalizations noted with CRT turned on versus off (N Engl J Med. 2013 Oct 10;369[15]:1395-405).

However, this still left open the question of the clinical significance of mechanical dyssynchrony in such patients. Dr. Gorcsan and coinvestigators conducted a secondary subgroup analysis of 614 EchoCRT participants with baseline and 6-month echocardiograms in order to provide the answer.

“Our hypothesis was that persistent or worsening dyssynchrony is associated with unfavorable outcomes,” explained Dr. Gorcsan, professor of medicine and director of echocardiography at the University of Pittsburgh.

This indeed turned out to be the case. Three-quarters of patients experienced persistent or worsening dyssynchrony as measured by tissue Doppler or speckle-tracking radial strain delay during 6 months of follow-up, and they were 1.54-fold more likely to experience the combined primary endpoint of death or heart failure hospitalization, compared with the 25% of patients who experienced improvement in their dyssynchrony.

Moreover, even after statistical adjustment for potential confounders including baseline QRS width, ejection fraction, and left ventricular end-diastolic diameter, persistent or worsening dyssynchrony at 6 months remained associated with a 1.57-fold increased likelihood of heart failure hospitalization.

CRT being turned on or off had no impact on whether a patient’s dyssynchrony improved or not during follow-up.

“We hypothesize that a reason for improvement in dyssynchrony may be in part due to favorable left ventricular reverse remodeling – 97% of patients were on a beta-blocker and 95% were on an ACE inhibitor or angiotensin receptor blocker – but the precise mechanism remains uncertain,” Dr. Gorcsan observed.

Simultaneous with Dr. Gorcsan’s presentation, the clinical update of the EchoCRT trial was published online (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv418).

In an accompanying editorial, Dr. Amil M. Shah and Dr. Scott D. Solomon of Brigham and Women’s Hospital, Boston, said the new EchoCRT findings suggest mechanical dyssynchrony is a risk factor – a marker of progressive contractile dysfunction – but not a viable treatment target. That’s worth bearing in mind because mechanical dyssynchrony is now under consideration as a potential therapeutic target in patients with heart failure with preserved ejection fraction and other populations with conditions other than those addressed in EchoCRT (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv458).

The EchoCRT trial was sponsored by Biotronik. Dr. Gorcsan reported receiving research grants from Biotronik, GE, Medtronic, and St. Jude.

bjancin@frontlinemedcom.com

LONDON – Persistent mechanical dyssynchrony in patients with heart failure with reduced ejection fraction and a narrow QRS width appears to be a new marker of heightened risk.

That’s the key take-away message of an update of the EchoCRT trial presented by Dr. John Gorcsan III at the annual congress of the European Society of Cardiology.

EchoCRT was a large, multicenter randomized trial of cardiac resynchronization therapy (CRT) in patients with severely symptomatic heart failure with a QRS width of less than 130 ms, a left ventricular ejection fraction of 35% or less, and echocardiographic evidence of dyssynchrony. It was a negative study, with no improvement in rates of death or heart failure hospitalizations noted with CRT turned on versus off (N Engl J Med. 2013 Oct 10;369[15]:1395-405).

However, this still left open the question of the clinical significance of mechanical dyssynchrony in such patients. Dr. Gorcsan and coinvestigators conducted a secondary subgroup analysis of 614 EchoCRT participants with baseline and 6-month echocardiograms in order to provide the answer.

“Our hypothesis was that persistent or worsening dyssynchrony is associated with unfavorable outcomes,” explained Dr. Gorcsan, professor of medicine and director of echocardiography at the University of Pittsburgh.

This indeed turned out to be the case. Three-quarters of patients experienced persistent or worsening dyssynchrony as measured by tissue Doppler or speckle-tracking radial strain delay during 6 months of follow-up, and they were 1.54-fold more likely to experience the combined primary endpoint of death or heart failure hospitalization, compared with the 25% of patients who experienced improvement in their dyssynchrony.

Moreover, even after statistical adjustment for potential confounders including baseline QRS width, ejection fraction, and left ventricular end-diastolic diameter, persistent or worsening dyssynchrony at 6 months remained associated with a 1.57-fold increased likelihood of heart failure hospitalization.

CRT being turned on or off had no impact on whether a patient’s dyssynchrony improved or not during follow-up.

“We hypothesize that a reason for improvement in dyssynchrony may be in part due to favorable left ventricular reverse remodeling – 97% of patients were on a beta-blocker and 95% were on an ACE inhibitor or angiotensin receptor blocker – but the precise mechanism remains uncertain,” Dr. Gorcsan observed.

Simultaneous with Dr. Gorcsan’s presentation, the clinical update of the EchoCRT trial was published online (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv418).

In an accompanying editorial, Dr. Amil M. Shah and Dr. Scott D. Solomon of Brigham and Women’s Hospital, Boston, said the new EchoCRT findings suggest mechanical dyssynchrony is a risk factor – a marker of progressive contractile dysfunction – but not a viable treatment target. That’s worth bearing in mind because mechanical dyssynchrony is now under consideration as a potential therapeutic target in patients with heart failure with preserved ejection fraction and other populations with conditions other than those addressed in EchoCRT (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv458).

The EchoCRT trial was sponsored by Biotronik. Dr. Gorcsan reported receiving research grants from Biotronik, GE, Medtronic, and St. Jude.

bjancin@frontlinemedcom.com

LONDON – Persistent mechanical dyssynchrony in patients with heart failure with reduced ejection fraction and a narrow QRS width appears to be a new marker of heightened risk.

That’s the key take-away message of an update of the EchoCRT trial presented by Dr. John Gorcsan III at the annual congress of the European Society of Cardiology.

EchoCRT was a large, multicenter randomized trial of cardiac resynchronization therapy (CRT) in patients with severely symptomatic heart failure with a QRS width of less than 130 ms, a left ventricular ejection fraction of 35% or less, and echocardiographic evidence of dyssynchrony. It was a negative study, with no improvement in rates of death or heart failure hospitalizations noted with CRT turned on versus off (N Engl J Med. 2013 Oct 10;369[15]:1395-405).

However, this still left open the question of the clinical significance of mechanical dyssynchrony in such patients. Dr. Gorcsan and coinvestigators conducted a secondary subgroup analysis of 614 EchoCRT participants with baseline and 6-month echocardiograms in order to provide the answer.

“Our hypothesis was that persistent or worsening dyssynchrony is associated with unfavorable outcomes,” explained Dr. Gorcsan, professor of medicine and director of echocardiography at the University of Pittsburgh.

This indeed turned out to be the case. Three-quarters of patients experienced persistent or worsening dyssynchrony as measured by tissue Doppler or speckle-tracking radial strain delay during 6 months of follow-up, and they were 1.54-fold more likely to experience the combined primary endpoint of death or heart failure hospitalization, compared with the 25% of patients who experienced improvement in their dyssynchrony.

Moreover, even after statistical adjustment for potential confounders including baseline QRS width, ejection fraction, and left ventricular end-diastolic diameter, persistent or worsening dyssynchrony at 6 months remained associated with a 1.57-fold increased likelihood of heart failure hospitalization.

CRT being turned on or off had no impact on whether a patient’s dyssynchrony improved or not during follow-up.

“We hypothesize that a reason for improvement in dyssynchrony may be in part due to favorable left ventricular reverse remodeling – 97% of patients were on a beta-blocker and 95% were on an ACE inhibitor or angiotensin receptor blocker – but the precise mechanism remains uncertain,” Dr. Gorcsan observed.

Simultaneous with Dr. Gorcsan’s presentation, the clinical update of the EchoCRT trial was published online (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv418).

In an accompanying editorial, Dr. Amil M. Shah and Dr. Scott D. Solomon of Brigham and Women’s Hospital, Boston, said the new EchoCRT findings suggest mechanical dyssynchrony is a risk factor – a marker of progressive contractile dysfunction – but not a viable treatment target. That’s worth bearing in mind because mechanical dyssynchrony is now under consideration as a potential therapeutic target in patients with heart failure with preserved ejection fraction and other populations with conditions other than those addressed in EchoCRT (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv458).

The EchoCRT trial was sponsored by Biotronik. Dr. Gorcsan reported receiving research grants from Biotronik, GE, Medtronic, and St. Jude.

bjancin@frontlinemedcom.com

LONDON – Persistent mechanical dyssynchrony in patients with heart failure with reduced ejection fraction and a narrow QRS width appears to be a new marker of heightened risk.

That’s the key take-away message of an update of the EchoCRT trial presented by Dr. John Gorcsan III at the annual congress of the European Society of Cardiology.

EchoCRT was a large, multicenter randomized trial of cardiac resynchronization therapy (CRT) in patients with severely symptomatic heart failure with a QRS width of less than 130 ms, a left ventricular ejection fraction of 35% or less, and echocardiographic evidence of dyssynchrony. It was a negative study, with no improvement in rates of death or heart failure hospitalizations noted with CRT turned on versus off (N Engl J Med. 2013 Oct 10;369[15]:1395-405).

However, this still left open the question of the clinical significance of mechanical dyssynchrony in such patients. Dr. Gorcsan and coinvestigators conducted a secondary subgroup analysis of 614 EchoCRT participants with baseline and 6-month echocardiograms in order to provide the answer.

“Our hypothesis was that persistent or worsening dyssynchrony is associated with unfavorable outcomes,” explained Dr. Gorcsan, professor of medicine and director of echocardiography at the University of Pittsburgh.

This indeed turned out to be the case. Three-quarters of patients experienced persistent or worsening dyssynchrony as measured by tissue Doppler or speckle-tracking radial strain delay during 6 months of follow-up, and they were 1.54-fold more likely to experience the combined primary endpoint of death or heart failure hospitalization, compared with the 25% of patients who experienced improvement in their dyssynchrony.

Moreover, even after statistical adjustment for potential confounders including baseline QRS width, ejection fraction, and left ventricular end-diastolic diameter, persistent or worsening dyssynchrony at 6 months remained associated with a 1.57-fold increased likelihood of heart failure hospitalization.

CRT being turned on or off had no impact on whether a patient’s dyssynchrony improved or not during follow-up.

“We hypothesize that a reason for improvement in dyssynchrony may be in part due to favorable left ventricular reverse remodeling – 97% of patients were on a beta-blocker and 95% were on an ACE inhibitor or angiotensin receptor blocker – but the precise mechanism remains uncertain,” Dr. Gorcsan observed.

Simultaneous with Dr. Gorcsan’s presentation, the clinical update of the EchoCRT trial was published online (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv418).

In an accompanying editorial, Dr. Amil M. Shah and Dr. Scott D. Solomon of Brigham and Women’s Hospital, Boston, said the new EchoCRT findings suggest mechanical dyssynchrony is a risk factor – a marker of progressive contractile dysfunction – but not a viable treatment target. That’s worth bearing in mind because mechanical dyssynchrony is now under consideration as a potential therapeutic target in patients with heart failure with preserved ejection fraction and other populations with conditions other than those addressed in EchoCRT (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv458).

The EchoCRT trial was sponsored by Biotronik. Dr. Gorcsan reported receiving research grants from Biotronik, GE, Medtronic, and St. Jude.

bjancin@frontlinemedcom.com

LONDON – Persistent mechanical dyssynchrony in patients with heart failure with reduced ejection fraction and a narrow QRS width appears to be a new marker of heightened risk.

That’s the key take-away message of an update of the EchoCRT trial presented by Dr. John Gorcsan III at the annual congress of the European Society of Cardiology.

EchoCRT was a large, multicenter randomized trial of cardiac resynchronization therapy (CRT) in patients with severely symptomatic heart failure with a QRS width of less than 130 ms, a left ventricular ejection fraction of 35% or less, and echocardiographic evidence of dyssynchrony. It was a negative study, with no improvement in rates of death or heart failure hospitalizations noted with CRT turned on versus off (N Engl J Med. 2013 Oct 10;369[15]:1395-405).

However, this still left open the question of the clinical significance of mechanical dyssynchrony in such patients. Dr. Gorcsan and coinvestigators conducted a secondary subgroup analysis of 614 EchoCRT participants with baseline and 6-month echocardiograms in order to provide the answer.

“Our hypothesis was that persistent or worsening dyssynchrony is associated with unfavorable outcomes,” explained Dr. Gorcsan, professor of medicine and director of echocardiography at the University of Pittsburgh.

This indeed turned out to be the case. Three-quarters of patients experienced persistent or worsening dyssynchrony as measured by tissue Doppler or speckle-tracking radial strain delay during 6 months of follow-up, and they were 1.54-fold more likely to experience the combined primary endpoint of death or heart failure hospitalization, compared with the 25% of patients who experienced improvement in their dyssynchrony.

Moreover, even after statistical adjustment for potential confounders including baseline QRS width, ejection fraction, and left ventricular end-diastolic diameter, persistent or worsening dyssynchrony at 6 months remained associated with a 1.57-fold increased likelihood of heart failure hospitalization.

CRT being turned on or off had no impact on whether a patient’s dyssynchrony improved or not during follow-up.

“We hypothesize that a reason for improvement in dyssynchrony may be in part due to favorable left ventricular reverse remodeling – 97% of patients were on a beta-blocker and 95% were on an ACE inhibitor or angiotensin receptor blocker – but the precise mechanism remains uncertain,” Dr. Gorcsan observed.

Simultaneous with Dr. Gorcsan’s presentation, the clinical update of the EchoCRT trial was published online (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv418).

In an accompanying editorial, Dr. Amil M. Shah and Dr. Scott D. Solomon of Brigham and Women’s Hospital, Boston, said the new EchoCRT findings suggest mechanical dyssynchrony is a risk factor – a marker of progressive contractile dysfunction – but not a viable treatment target. That’s worth bearing in mind because mechanical dyssynchrony is now under consideration as a potential therapeutic target in patients with heart failure with preserved ejection fraction and other populations with conditions other than those addressed in EchoCRT (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv458).

The EchoCRT trial was sponsored by Biotronik. Dr. Gorcsan reported receiving research grants from Biotronik, GE, Medtronic, and St. Jude.

bjancin@frontlinemedcom.com

LONDON – Persistent mechanical dyssynchrony in patients with heart failure with reduced ejection fraction and a narrow QRS width appears to be a new marker of heightened risk.

That’s the key take-away message of an update of the EchoCRT trial presented by Dr. John Gorcsan III at the annual congress of the European Society of Cardiology.

EchoCRT was a large, multicenter randomized trial of cardiac resynchronization therapy (CRT) in patients with severely symptomatic heart failure with a QRS width of less than 130 ms, a left ventricular ejection fraction of 35% or less, and echocardiographic evidence of dyssynchrony. It was a negative study, with no improvement in rates of death or heart failure hospitalizations noted with CRT turned on versus off (N Engl J Med. 2013 Oct 10;369[15]:1395-405).

However, this still left open the question of the clinical significance of mechanical dyssynchrony in such patients. Dr. Gorcsan and coinvestigators conducted a secondary subgroup analysis of 614 EchoCRT participants with baseline and 6-month echocardiograms in order to provide the answer.

“Our hypothesis was that persistent or worsening dyssynchrony is associated with unfavorable outcomes,” explained Dr. Gorcsan, professor of medicine and director of echocardiography at the University of Pittsburgh.

This indeed turned out to be the case. Three-quarters of patients experienced persistent or worsening dyssynchrony as measured by tissue Doppler or speckle-tracking radial strain delay during 6 months of follow-up, and they were 1.54-fold more likely to experience the combined primary endpoint of death or heart failure hospitalization, compared with the 25% of patients who experienced improvement in their dyssynchrony.

Moreover, even after statistical adjustment for potential confounders including baseline QRS width, ejection fraction, and left ventricular end-diastolic diameter, persistent or worsening dyssynchrony at 6 months remained associated with a 1.57-fold increased likelihood of heart failure hospitalization.

CRT being turned on or off had no impact on whether a patient’s dyssynchrony improved or not during follow-up.

“We hypothesize that a reason for improvement in dyssynchrony may be in part due to favorable left ventricular reverse remodeling – 97% of patients were on a beta-blocker and 95% were on an ACE inhibitor or angiotensin receptor blocker – but the precise mechanism remains uncertain,” Dr. Gorcsan observed.

Simultaneous with Dr. Gorcsan’s presentation, the clinical update of the EchoCRT trial was published online (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv418).

In an accompanying editorial, Dr. Amil M. Shah and Dr. Scott D. Solomon of Brigham and Women’s Hospital, Boston, said the new EchoCRT findings suggest mechanical dyssynchrony is a risk factor – a marker of progressive contractile dysfunction – but not a viable treatment target. That’s worth bearing in mind because mechanical dyssynchrony is now under consideration as a potential therapeutic target in patients with heart failure with preserved ejection fraction and other populations with conditions other than those addressed in EchoCRT (Eur Heart J. 2015 Aug 30. doi: 10.1093/eurheartj/ehv458).

The EchoCRT trial was sponsored by Biotronik. Dr. Gorcsan reported receiving research grants from Biotronik, GE, Medtronic, and St. Jude.

bjancin@frontlinemedcom.com

LONDON – Adult patients with chronic heart failure had an average 51% increased incidence of all forms of cancer, compared with the general population in an analysis of more than 9,000 Danish patients treated for heart failure during 2002-2009.

Although the study did not address causality, the elevated risk for new-onset cancers in heart failure patients may stem from shared risk factors for the two diseases, Dr. Ann Banke said at the annual congress of the European Society of Cardiology. Smoking, for example, is a potential etiologic factor for both heart failure and certain cancers. Other potential shared risk factors could include other types of unhealthy lifestyle choices, and a heightened inflammatory state, suggested Dr. Banke, a researcher in the department of cardiology at Odense (Denmark) University Hospital.

Mitchel L. Zoler/Frontline Medical News

“Increased awareness of the risk for development of cancer in heart failure patients is warranted,” especially given the relatively long life expectancy now seen among many patients with chronic heart failure, Dr. Banke said.

She and her associates reviewed 9,307 Danish patients with chronic heart failure and no history of cancer who entered a national heart failure cohort during 2002-2009. Their average age was 68 years, 73% were men, 89% had heart failure with reduced ejection fraction, 80% had New York Heart Association class I or II heart failure, and 15% had diabetes. During follow-up through 2013, a total of 975 of these patients received a diagnosis of cancer. The researchers compared the incidence rate of cancer among these heart failure patients with the rate in the general Danish adult population in the same 2002-2013 period, during which the general population developed 330,843 cancers.

In an analysis that adjusted for age and sex, the heart failure patients had a statistically significant 51% increased rate of incidence cancers of all types (P less than .0001). When broken down by cancer site, the heart failure patients showed significantly increased rates for all types of cancers except prostate cancer (see chart). Dr. Banke speculated that the absence of an increased incidence rate in prostate cancer among heart failure patients may reflect the age of the heart failure patients, or perhaps because prostate cancer does not share as many risk factors with heart failure as do the other cancer types.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LONDON – Adult patients with chronic heart failure had an average 51% increased incidence of all forms of cancer, compared with the general population in an analysis of more than 9,000 Danish patients treated for heart failure during 2002-2009.

Although the study did not address causality, the elevated risk for new-onset cancers in heart failure patients may stem from shared risk factors for the two diseases, Dr. Ann Banke said at the annual congress of the European Society of Cardiology. Smoking, for example, is a potential etiologic factor for both heart failure and certain cancers. Other potential shared risk factors could include other types of unhealthy lifestyle choices, and a heightened inflammatory state, suggested Dr. Banke, a researcher in the department of cardiology at Odense (Denmark) University Hospital.

Mitchel L. Zoler/Frontline Medical News

“Increased awareness of the risk for development of cancer in heart failure patients is warranted,” especially given the relatively long life expectancy now seen among many patients with chronic heart failure, Dr. Banke said.

She and her associates reviewed 9,307 Danish patients with chronic heart failure and no history of cancer who entered a national heart failure cohort during 2002-2009. Their average age was 68 years, 73% were men, 89% had heart failure with reduced ejection fraction, 80% had New York Heart Association class I or II heart failure, and 15% had diabetes. During follow-up through 2013, a total of 975 of these patients received a diagnosis of cancer. The researchers compared the incidence rate of cancer among these heart failure patients with the rate in the general Danish adult population in the same 2002-2013 period, during which the general population developed 330,843 cancers.

In an analysis that adjusted for age and sex, the heart failure patients had a statistically significant 51% increased rate of incidence cancers of all types (P less than .0001). When broken down by cancer site, the heart failure patients showed significantly increased rates for all types of cancers except prostate cancer (see chart). Dr. Banke speculated that the absence of an increased incidence rate in prostate cancer among heart failure patients may reflect the age of the heart failure patients, or perhaps because prostate cancer does not share as many risk factors with heart failure as do the other cancer types.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

LONDON – Adult patients with chronic heart failure had an average 51% increased incidence of all forms of cancer, compared with the general population in an analysis of more than 9,000 Danish patients treated for heart failure during 2002-2009.

Although the study did not address causality, the elevated risk for new-onset cancers in heart failure patients may stem from shared risk factors for the two diseases, Dr. Ann Banke said at the annual congress of the European Society of Cardiology. Smoking, for example, is a potential etiologic factor for both heart failure and certain cancers. Other potential shared risk factors could include other types of unhealthy lifestyle choices, and a heightened inflammatory state, suggested Dr. Banke, a researcher in the department of cardiology at Odense (Denmark) University Hospital.

Mitchel L. Zoler/Frontline Medical News

“Increased awareness of the risk for development of cancer in heart failure patients is warranted,” especially given the relatively long life expectancy now seen among many patients with chronic heart failure, Dr. Banke said.

She and her associates reviewed 9,307 Danish patients with chronic heart failure and no history of cancer who entered a national heart failure cohort during 2002-2009. Their average age was 68 years, 73% were men, 89% had heart failure with reduced ejection fraction, 80% had New York Heart Association class I or II heart failure, and 15% had diabetes. During follow-up through 2013, a total of 975 of these patients received a diagnosis of cancer. The researchers compared the incidence rate of cancer among these heart failure patients with the rate in the general Danish adult population in the same 2002-2013 period, during which the general population developed 330,843 cancers.

In an analysis that adjusted for age and sex, the heart failure patients had a statistically significant 51% increased rate of incidence cancers of all types (P less than .0001). When broken down by cancer site, the heart failure patients showed significantly increased rates for all types of cancers except prostate cancer (see chart). Dr. Banke speculated that the absence of an increased incidence rate in prostate cancer among heart failure patients may reflect the age of the heart failure patients, or perhaps because prostate cancer does not share as many risk factors with heart failure as do the other cancer types.

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