Heart Failure

SAN DIEGO – A series of reports in 2014 from several independent groups implicated heart failure as a trigger of type 2 diabetes; findings from several of the analyses also suggested that relief of congestion can result in rapid resolution of the diabetes.

The best way to manage new-onset diabetes in heart failure patients is to “minimize the congestion,” and to “try to achieve as good control of the heart failure as possible,” said Dr. Maya Guglin during a talk at the annual meeting of the American College of Cardiology, in which she laid out the evidence for this newly recognized form of type 2 diabetes. In a review she published in 2014, Dr. Guglin coined the term “cardiogenic diabetes” to describe the condition (Heart Fail. Rev. 2014;19:595-602).

Dr. Guglin traced the data trail for cardiogenic diabetes starting in a 2011 retrospective study of 15 patients with advanced heart failure who received a left ventricular assist device (LVAD) at Columbia University in New York (Eur. J. Heart Fail. 2011;13:195-9). These 15, about a third of the 43 total LVAD recipients at Columbia at the time, had been diagnosed with type 2 diabetes for an average of 6 years before receiving the device. Just before they got their device, their average hemoglobin A_1c (HbA_1c) level was 7.7%, and their average fasting plasma glucose level was 158 mg/dL. An average of 4 months later, their mean HbA_1c had dropped to 6%, and their mean fasting glucose had fallen to 104 mg/dL. Six patients were completely off any diabetes medication. All this occurred while patients had a small increase in their body mass index, which Dr. Guglin attributed to their better physical condition and improved appetite.

Last year, another four reports appeared from four independent, U.S. heart failure groups with results that mirrored the Columbia experience. Dr. Guglin and her associates at the University of Kentucky, Lexington, reported their experience with 50 patients who received an LVAD during 2002-2012 and had type 2 diabetes just before they received a device, with an average HbA_1c of 7.6%. Three months after LVAD placement, their average HbA_1c had dropped to 5.7%, and 9-12 months after device placement, their average HbA_1c level was 5.3% (ASAIO J. 2014;60:290-3). As in the Columbia series, these improvements in hyperglycemia occurred without any significant change in body mass index.

Dr. Guglin also cited similar findings in 50 LVAD patients treated at the University of Rochester (N.Y.)(ASAIO J. 2014;60:675-80), 28 LVAD patients at Penn State Medical College in Hershey, Pa. (Heart Surg. Forum 2014;17:E98-102), and 66 LVAD patients from the University of Illinois in Chicago (Eur. J. Heart Fail. 2014;16:1120-4). In these reports type 2 diabetes existed in roughly a quarter to a third of patients with advanced heart failure who qualified for an LVAD just prior to the time they received the device.

Dr. Guglin also cited two epidemiologic analyses with complementary findings on the risk for incident diabetes faced by heart failure patients. She and her associates reviewed data from 3,165 elderly Americans free from diabetes enrolled in the Cardiovascular Health Study. This cohort included 80 patients with heart failure and 3,085 without heart failure. During 3-4 years of follow-up, 6% of the heart failure patients developed new-onset diabetes, and an additional 10% developed new-onset impaired fasting glucose. In contrast, these incidence rates were 1.5% and 5%, respectively, in the enrollees without heart failure at baseline. In an analysis that controlled for several demographic and biomedical factors, heart failure linked with a statistically significant, 2.4-fold increased risk for the development of diabetes (Cardiology 2014;129:84-92).

And a Danish nationwide cohort study of more than 99,000 residents discharged from a first-time hospitalization for heart failure during 1997-2010 showed a statistically significant link between heart failure severity and an increased rate of development of incident diabetes using diuretic treatment dosage as a surrogate measure of heart failure severity (Diabetologia 2014;57:1595-1600).

The apparent impact of LVAD placement on type 2 diabetes contrasts with what happens in patients who receive a heart transplant, where this association has not been seen. Dr. Guglin suggested that may be because of the immunosuppression with steroids that heart transplant recipients receive, treatment that also prevents diabetes resolution, she said.

“It all boils down to congestion,” Dr. Guglin said in an interview. “Control congestion as much as possible to control the diabetes.”

Dr. Guglin had no relevant financial disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

SAN DIEGO – A series of reports in 2014 from several independent groups implicated heart failure as a trigger of type 2 diabetes; findings from several of the analyses also suggested that relief of congestion can result in rapid resolution of the diabetes.

The best way to manage new-onset diabetes in heart failure patients is to “minimize the congestion,” and to “try to achieve as good control of the heart failure as possible,” said Dr. Maya Guglin during a talk at the annual meeting of the American College of Cardiology, in which she laid out the evidence for this newly recognized form of type 2 diabetes. In a review she published in 2014, Dr. Guglin coined the term “cardiogenic diabetes” to describe the condition (Heart Fail. Rev. 2014;19:595-602).

Dr. Guglin traced the data trail for cardiogenic diabetes starting in a 2011 retrospective study of 15 patients with advanced heart failure who received a left ventricular assist device (LVAD) at Columbia University in New York (Eur. J. Heart Fail. 2011;13:195-9). These 15, about a third of the 43 total LVAD recipients at Columbia at the time, had been diagnosed with type 2 diabetes for an average of 6 years before receiving the device. Just before they got their device, their average hemoglobin A_1c (HbA_1c) level was 7.7%, and their average fasting plasma glucose level was 158 mg/dL. An average of 4 months later, their mean HbA_1c had dropped to 6%, and their mean fasting glucose had fallen to 104 mg/dL. Six patients were completely off any diabetes medication. All this occurred while patients had a small increase in their body mass index, which Dr. Guglin attributed to their better physical condition and improved appetite.

Last year, another four reports appeared from four independent, U.S. heart failure groups with results that mirrored the Columbia experience. Dr. Guglin and her associates at the University of Kentucky, Lexington, reported their experience with 50 patients who received an LVAD during 2002-2012 and had type 2 diabetes just before they received a device, with an average HbA_1c of 7.6%. Three months after LVAD placement, their average HbA_1c had dropped to 5.7%, and 9-12 months after device placement, their average HbA_1c level was 5.3% (ASAIO J. 2014;60:290-3). As in the Columbia series, these improvements in hyperglycemia occurred without any significant change in body mass index.

Dr. Guglin also cited similar findings in 50 LVAD patients treated at the University of Rochester (N.Y.)(ASAIO J. 2014;60:675-80), 28 LVAD patients at Penn State Medical College in Hershey, Pa. (Heart Surg. Forum 2014;17:E98-102), and 66 LVAD patients from the University of Illinois in Chicago (Eur. J. Heart Fail. 2014;16:1120-4). In these reports type 2 diabetes existed in roughly a quarter to a third of patients with advanced heart failure who qualified for an LVAD just prior to the time they received the device.

Dr. Guglin also cited two epidemiologic analyses with complementary findings on the risk for incident diabetes faced by heart failure patients. She and her associates reviewed data from 3,165 elderly Americans free from diabetes enrolled in the Cardiovascular Health Study. This cohort included 80 patients with heart failure and 3,085 without heart failure. During 3-4 years of follow-up, 6% of the heart failure patients developed new-onset diabetes, and an additional 10% developed new-onset impaired fasting glucose. In contrast, these incidence rates were 1.5% and 5%, respectively, in the enrollees without heart failure at baseline. In an analysis that controlled for several demographic and biomedical factors, heart failure linked with a statistically significant, 2.4-fold increased risk for the development of diabetes (Cardiology 2014;129:84-92).

And a Danish nationwide cohort study of more than 99,000 residents discharged from a first-time hospitalization for heart failure during 1997-2010 showed a statistically significant link between heart failure severity and an increased rate of development of incident diabetes using diuretic treatment dosage as a surrogate measure of heart failure severity (Diabetologia 2014;57:1595-1600).

The apparent impact of LVAD placement on type 2 diabetes contrasts with what happens in patients who receive a heart transplant, where this association has not been seen. Dr. Guglin suggested that may be because of the immunosuppression with steroids that heart transplant recipients receive, treatment that also prevents diabetes resolution, she said.

“It all boils down to congestion,” Dr. Guglin said in an interview. “Control congestion as much as possible to control the diabetes.”

Dr. Guglin had no relevant financial disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

SAN DIEGO – A series of reports in 2014 from several independent groups implicated heart failure as a trigger of type 2 diabetes; findings from several of the analyses also suggested that relief of congestion can result in rapid resolution of the diabetes.

The best way to manage new-onset diabetes in heart failure patients is to “minimize the congestion,” and to “try to achieve as good control of the heart failure as possible,” said Dr. Maya Guglin during a talk at the annual meeting of the American College of Cardiology, in which she laid out the evidence for this newly recognized form of type 2 diabetes. In a review she published in 2014, Dr. Guglin coined the term “cardiogenic diabetes” to describe the condition (Heart Fail. Rev. 2014;19:595-602).

Dr. Guglin traced the data trail for cardiogenic diabetes starting in a 2011 retrospective study of 15 patients with advanced heart failure who received a left ventricular assist device (LVAD) at Columbia University in New York (Eur. J. Heart Fail. 2011;13:195-9). These 15, about a third of the 43 total LVAD recipients at Columbia at the time, had been diagnosed with type 2 diabetes for an average of 6 years before receiving the device. Just before they got their device, their average hemoglobin A_1c (HbA_1c) level was 7.7%, and their average fasting plasma glucose level was 158 mg/dL. An average of 4 months later, their mean HbA_1c had dropped to 6%, and their mean fasting glucose had fallen to 104 mg/dL. Six patients were completely off any diabetes medication. All this occurred while patients had a small increase in their body mass index, which Dr. Guglin attributed to their better physical condition and improved appetite.

Last year, another four reports appeared from four independent, U.S. heart failure groups with results that mirrored the Columbia experience. Dr. Guglin and her associates at the University of Kentucky, Lexington, reported their experience with 50 patients who received an LVAD during 2002-2012 and had type 2 diabetes just before they received a device, with an average HbA_1c of 7.6%. Three months after LVAD placement, their average HbA_1c had dropped to 5.7%, and 9-12 months after device placement, their average HbA_1c level was 5.3% (ASAIO J. 2014;60:290-3). As in the Columbia series, these improvements in hyperglycemia occurred without any significant change in body mass index.

Dr. Guglin also cited similar findings in 50 LVAD patients treated at the University of Rochester (N.Y.)(ASAIO J. 2014;60:675-80), 28 LVAD patients at Penn State Medical College in Hershey, Pa. (Heart Surg. Forum 2014;17:E98-102), and 66 LVAD patients from the University of Illinois in Chicago (Eur. J. Heart Fail. 2014;16:1120-4). In these reports type 2 diabetes existed in roughly a quarter to a third of patients with advanced heart failure who qualified for an LVAD just prior to the time they received the device.

Dr. Guglin also cited two epidemiologic analyses with complementary findings on the risk for incident diabetes faced by heart failure patients. She and her associates reviewed data from 3,165 elderly Americans free from diabetes enrolled in the Cardiovascular Health Study. This cohort included 80 patients with heart failure and 3,085 without heart failure. During 3-4 years of follow-up, 6% of the heart failure patients developed new-onset diabetes, and an additional 10% developed new-onset impaired fasting glucose. In contrast, these incidence rates were 1.5% and 5%, respectively, in the enrollees without heart failure at baseline. In an analysis that controlled for several demographic and biomedical factors, heart failure linked with a statistically significant, 2.4-fold increased risk for the development of diabetes (Cardiology 2014;129:84-92).

And a Danish nationwide cohort study of more than 99,000 residents discharged from a first-time hospitalization for heart failure during 1997-2010 showed a statistically significant link between heart failure severity and an increased rate of development of incident diabetes using diuretic treatment dosage as a surrogate measure of heart failure severity (Diabetologia 2014;57:1595-1600).

The apparent impact of LVAD placement on type 2 diabetes contrasts with what happens in patients who receive a heart transplant, where this association has not been seen. Dr. Guglin suggested that may be because of the immunosuppression with steroids that heart transplant recipients receive, treatment that also prevents diabetes resolution, she said.

“It all boils down to congestion,” Dr. Guglin said in an interview. “Control congestion as much as possible to control the diabetes.”

Dr. Guglin had no relevant financial disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

SAN DIEGO – Beefing up a sick left ventricle via a set of injections of an inert alginate hydrogel resulted in significantly improved functional capacity, compared with optimal medical therapy through 6 months of follow-up in patients with advanced heart failure in the randomized AUGMENT-HF trial.

Investigators also noted “an interesting and striking reduction” in hospitalizations for worsening heart failure in the group that received left ventricular (LV) augmentation with the material, known as Algisyl-LVR, Dr. Stefan D. Anker reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

Indeed, among 78 patients with advanced heart failure randomized to hydrogel injections plus optimal medical therapy or to optimal medical therapy alone, there were 14 hospitalizations for worsening heart failure in eight controls, compared with 5 hospitalizations in four patients in the LV augmentation group. The between-group difference is large, but the number of hospitalizations is still small. AUGMENT-HF will continue for 2 years of follow-up.

“This gives us hope for the future,” said Dr. Anker, professor of cardiology and cachexia research at Charité Medical School, Berlin.

In addition, based upon the favorable 6-month study results, planning is underway for a larger, pivotal phase III U.S. trial of Algisyl-LVR, classified as a medical device, to start later this year.

At present, surgeons implant the hydrogel through a minithoracotomy. The procedure involves 10-20 injections totaling 4-5 mL of the inert, permanent material, which is placed as a ring of beads along a circumferential line at the left ventricular midwall.

“We make the wall thicker and the cavity of the ventricle a little smaller, thereby reducing wall stress. We basically try to change the physics of the pump action of the heart to improve patient status and perhaps patient outcome,” Dr. Anker explained.

Surgeons say it’s an easily learned procedure. The surgical morbidity and mortality seen in AUGMENT-HF were deemed acceptable by investigators and the study sponsor, so this new therapy will initially be developed as a surgical procedure. But it’s certainly a treatment that lends itself to delivery by percutaneous catheter in the future, according to the cardiologist.

Study participants had moderate to severe heart failure, with an average LV ejection fraction of 25%. Most were New York Heart Association (NYHA) functional class III.

The primary study endpoint was change in peak oxygen uptake (VO₂) at 6 months from a baseline of 12.2 mL/kg/min. The value improved to 13.5 mL/kg/min in the LV augmentation group, compared with 12.4 mL/kg/min in controls, a between-group difference that Dr. Anker characterized as clinically relevant. He noted that one of the study’s strengths was that each peak VO₂ result was the average of two tests performed on the same occasion, a method that markedly improves test reproducibility.

Also, 6-minute walk distance improved in the LV augmentation group by a mean of 84.7 meters from a baseline 280 meters, while decreasing by 15.4 meters in controls.

“This is quite a positive result rarely seen with other therapies. For everybody involved, this was a very positive finding,” Dr. Anker said.

Among controls, NYHC class stayed steady over the course of 6 months while showing a 0.9-class improvement in the LV augmentation group.

Heart failure etiology – ischemic versus nonischemic – had no bearing on LV augmentation’s effectiveness. Baseline 6-minute walk distance did, though. Patients with a baseline walk distance of less than 287 meters experienced a much larger treatment effect: a mean 2.42 mL/kg/min greater improvement from baseline to 6 months with LV augmentation than in controls, as compared with a nonsignificant 0.4 mL/kg/min advantage among patients who covered more than 287 meters at baseline.

The mean procedure time was 80 minutes, with 190 minutes of anesthesia time. Patients spent an average of 2 days in the ICU.

Three deaths occurred in the surgical group within the first 30 days. Excluding the index hospitalization, there were 22 major adverse cardiovascular events in the control group and 9 in the LV augmentation group. Among these were three cardiovascular deaths in each study arm, for a total of six deaths through 6 months in the LV augmentation patients. However, with additional study follow-up beyond the 6 months presented at ACC 15, mortality has evened out in the two groups, according to Dr. Anker. Sustained ventricular tachycardia occurred in four controls and one patient who received LV augmentation. Several audience members expressed surprise at the low arrhythmia rate in the LV augmentation group, but Dr. Anker’s coinvestigator Dr. Douglas L. Mann explained that the implantation doesn’t create an isthmus, thus there is no nidus for arrhythmia formation.

“No arrhythmia signal has been seen. There is actually a reduction in both atrial and ventricular arrhythmias,” said Dr. Mann, professor of internal medicine and chief of the division of cardiovascular medicine at Washington University in St. Louis.

The AUGMENT-HF trial was sponsored by LoneStar Heart. Dr. Anker reported having no financial relationship with LoneStar, although he serves as a consultant to half a dozen other health care companies.

bjancin@frontlinemedcom.com

SAN DIEGO – Beefing up a sick left ventricle via a set of injections of an inert alginate hydrogel resulted in significantly improved functional capacity, compared with optimal medical therapy through 6 months of follow-up in patients with advanced heart failure in the randomized AUGMENT-HF trial.

Investigators also noted “an interesting and striking reduction” in hospitalizations for worsening heart failure in the group that received left ventricular (LV) augmentation with the material, known as Algisyl-LVR, Dr. Stefan D. Anker reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

Indeed, among 78 patients with advanced heart failure randomized to hydrogel injections plus optimal medical therapy or to optimal medical therapy alone, there were 14 hospitalizations for worsening heart failure in eight controls, compared with 5 hospitalizations in four patients in the LV augmentation group. The between-group difference is large, but the number of hospitalizations is still small. AUGMENT-HF will continue for 2 years of follow-up.

“This gives us hope for the future,” said Dr. Anker, professor of cardiology and cachexia research at Charité Medical School, Berlin.

In addition, based upon the favorable 6-month study results, planning is underway for a larger, pivotal phase III U.S. trial of Algisyl-LVR, classified as a medical device, to start later this year.

At present, surgeons implant the hydrogel through a minithoracotomy. The procedure involves 10-20 injections totaling 4-5 mL of the inert, permanent material, which is placed as a ring of beads along a circumferential line at the left ventricular midwall.

“We make the wall thicker and the cavity of the ventricle a little smaller, thereby reducing wall stress. We basically try to change the physics of the pump action of the heart to improve patient status and perhaps patient outcome,” Dr. Anker explained.

Surgeons say it’s an easily learned procedure. The surgical morbidity and mortality seen in AUGMENT-HF were deemed acceptable by investigators and the study sponsor, so this new therapy will initially be developed as a surgical procedure. But it’s certainly a treatment that lends itself to delivery by percutaneous catheter in the future, according to the cardiologist.

Study participants had moderate to severe heart failure, with an average LV ejection fraction of 25%. Most were New York Heart Association (NYHA) functional class III.

The primary study endpoint was change in peak oxygen uptake (VO₂) at 6 months from a baseline of 12.2 mL/kg/min. The value improved to 13.5 mL/kg/min in the LV augmentation group, compared with 12.4 mL/kg/min in controls, a between-group difference that Dr. Anker characterized as clinically relevant. He noted that one of the study’s strengths was that each peak VO₂ result was the average of two tests performed on the same occasion, a method that markedly improves test reproducibility.

Also, 6-minute walk distance improved in the LV augmentation group by a mean of 84.7 meters from a baseline 280 meters, while decreasing by 15.4 meters in controls.

“This is quite a positive result rarely seen with other therapies. For everybody involved, this was a very positive finding,” Dr. Anker said.

Among controls, NYHC class stayed steady over the course of 6 months while showing a 0.9-class improvement in the LV augmentation group.

Heart failure etiology – ischemic versus nonischemic – had no bearing on LV augmentation’s effectiveness. Baseline 6-minute walk distance did, though. Patients with a baseline walk distance of less than 287 meters experienced a much larger treatment effect: a mean 2.42 mL/kg/min greater improvement from baseline to 6 months with LV augmentation than in controls, as compared with a nonsignificant 0.4 mL/kg/min advantage among patients who covered more than 287 meters at baseline.

The mean procedure time was 80 minutes, with 190 minutes of anesthesia time. Patients spent an average of 2 days in the ICU.

Three deaths occurred in the surgical group within the first 30 days. Excluding the index hospitalization, there were 22 major adverse cardiovascular events in the control group and 9 in the LV augmentation group. Among these were three cardiovascular deaths in each study arm, for a total of six deaths through 6 months in the LV augmentation patients. However, with additional study follow-up beyond the 6 months presented at ACC 15, mortality has evened out in the two groups, according to Dr. Anker. Sustained ventricular tachycardia occurred in four controls and one patient who received LV augmentation. Several audience members expressed surprise at the low arrhythmia rate in the LV augmentation group, but Dr. Anker’s coinvestigator Dr. Douglas L. Mann explained that the implantation doesn’t create an isthmus, thus there is no nidus for arrhythmia formation.

“No arrhythmia signal has been seen. There is actually a reduction in both atrial and ventricular arrhythmias,” said Dr. Mann, professor of internal medicine and chief of the division of cardiovascular medicine at Washington University in St. Louis.

The AUGMENT-HF trial was sponsored by LoneStar Heart. Dr. Anker reported having no financial relationship with LoneStar, although he serves as a consultant to half a dozen other health care companies.

bjancin@frontlinemedcom.com

SAN DIEGO – Beefing up a sick left ventricle via a set of injections of an inert alginate hydrogel resulted in significantly improved functional capacity, compared with optimal medical therapy through 6 months of follow-up in patients with advanced heart failure in the randomized AUGMENT-HF trial.

Investigators also noted “an interesting and striking reduction” in hospitalizations for worsening heart failure in the group that received left ventricular (LV) augmentation with the material, known as Algisyl-LVR, Dr. Stefan D. Anker reported at the annual meeting of the American College of Cardiology.

Bruce Jancin/Frontline Medical News

Indeed, among 78 patients with advanced heart failure randomized to hydrogel injections plus optimal medical therapy or to optimal medical therapy alone, there were 14 hospitalizations for worsening heart failure in eight controls, compared with 5 hospitalizations in four patients in the LV augmentation group. The between-group difference is large, but the number of hospitalizations is still small. AUGMENT-HF will continue for 2 years of follow-up.

“This gives us hope for the future,” said Dr. Anker, professor of cardiology and cachexia research at Charité Medical School, Berlin.

In addition, based upon the favorable 6-month study results, planning is underway for a larger, pivotal phase III U.S. trial of Algisyl-LVR, classified as a medical device, to start later this year.

At present, surgeons implant the hydrogel through a minithoracotomy. The procedure involves 10-20 injections totaling 4-5 mL of the inert, permanent material, which is placed as a ring of beads along a circumferential line at the left ventricular midwall.

“We make the wall thicker and the cavity of the ventricle a little smaller, thereby reducing wall stress. We basically try to change the physics of the pump action of the heart to improve patient status and perhaps patient outcome,” Dr. Anker explained.

Surgeons say it’s an easily learned procedure. The surgical morbidity and mortality seen in AUGMENT-HF were deemed acceptable by investigators and the study sponsor, so this new therapy will initially be developed as a surgical procedure. But it’s certainly a treatment that lends itself to delivery by percutaneous catheter in the future, according to the cardiologist.

Study participants had moderate to severe heart failure, with an average LV ejection fraction of 25%. Most were New York Heart Association (NYHA) functional class III.

The primary study endpoint was change in peak oxygen uptake (VO₂) at 6 months from a baseline of 12.2 mL/kg/min. The value improved to 13.5 mL/kg/min in the LV augmentation group, compared with 12.4 mL/kg/min in controls, a between-group difference that Dr. Anker characterized as clinically relevant. He noted that one of the study’s strengths was that each peak VO₂ result was the average of two tests performed on the same occasion, a method that markedly improves test reproducibility.

Also, 6-minute walk distance improved in the LV augmentation group by a mean of 84.7 meters from a baseline 280 meters, while decreasing by 15.4 meters in controls.

“This is quite a positive result rarely seen with other therapies. For everybody involved, this was a very positive finding,” Dr. Anker said.

Among controls, NYHC class stayed steady over the course of 6 months while showing a 0.9-class improvement in the LV augmentation group.

Heart failure etiology – ischemic versus nonischemic – had no bearing on LV augmentation’s effectiveness. Baseline 6-minute walk distance did, though. Patients with a baseline walk distance of less than 287 meters experienced a much larger treatment effect: a mean 2.42 mL/kg/min greater improvement from baseline to 6 months with LV augmentation than in controls, as compared with a nonsignificant 0.4 mL/kg/min advantage among patients who covered more than 287 meters at baseline.

The mean procedure time was 80 minutes, with 190 minutes of anesthesia time. Patients spent an average of 2 days in the ICU.

Three deaths occurred in the surgical group within the first 30 days. Excluding the index hospitalization, there were 22 major adverse cardiovascular events in the control group and 9 in the LV augmentation group. Among these were three cardiovascular deaths in each study arm, for a total of six deaths through 6 months in the LV augmentation patients. However, with additional study follow-up beyond the 6 months presented at ACC 15, mortality has evened out in the two groups, according to Dr. Anker. Sustained ventricular tachycardia occurred in four controls and one patient who received LV augmentation. Several audience members expressed surprise at the low arrhythmia rate in the LV augmentation group, but Dr. Anker’s coinvestigator Dr. Douglas L. Mann explained that the implantation doesn’t create an isthmus, thus there is no nidus for arrhythmia formation.

“No arrhythmia signal has been seen. There is actually a reduction in both atrial and ventricular arrhythmias,” said Dr. Mann, professor of internal medicine and chief of the division of cardiovascular medicine at Washington University in St. Louis.

The AUGMENT-HF trial was sponsored by LoneStar Heart. Dr. Anker reported having no financial relationship with LoneStar, although he serves as a consultant to half a dozen other health care companies.

bjancin@frontlinemedcom.com

SAN DIEGO – Patients with major depressive disorder and heart failure with reduced ejection fraction fared no better with a selective serotonin reuptake inhibitor than with placebo in terms of heart failure outcomes or improved psychological well being in MOOD-HF, the first large randomized trial to examine the issue.

“MOOD-HF does not provide a rationale for the use of escitalopram in patients with systolic heart failure and comorbid depression. MOOD-HF suggests, however, that optimal heart failure management resulting in improved signs and symptoms might possibly be a means to ameliorate comorbid depression,” Dr. Christiane E. Angermann said at the annual meeting of the American College of Cardiology.

Moreover, exploratory secondary analysis suggested “a very subtle long-term effect of the antidepressant that may not be so favorable” in patients with more severe heart failure, she added.

“It seems that some of our patients take antidepressants in vain, and we should care more about the heart failure medications,” said Dr. Angermann, chairman of the MOOD-HF trial and director of clinical research at the Comprehensive Heart Failure Center at the University of Wurzburg (Germany).

MOOD-HF was an ambitious clinical trial conducted at 16 German academic medical centers. The study began with the screening – via the Patient Health Questionnaire–9 – of more than 11,000 patients who had heart failure with reduced ejection fraction. A psychiatrist using the Structured Clinical Interview for Depression eventually diagnosed a subgroup as having major depressive disorder. Ultimately, 372 patients with an average left ventricular ejection fraction of 35% were randomized in double-blind fashion to escitalopram (Lexapro) or placebo for a planned 24 months.

The study rationale stemmed from the well-established finding that depression is three to five times more common in heart failure patients than in the general population, and that the severity of depression in these patients shows a dose-response relationship with their risks of all-cause mortality and heart failure hospitalization. The primary study hypothesis in MOOD-HF was that treating the comorbid depression would result in a reduced risk of all-cause mortality and unplanned hospitalization for any cause.

“Never before had an ethics committee been persuaded to allow patients with major depressive disorder to be on a placebo for 2 years,” said Dr. Angermann. “It took a lot of discussion with the psychiatrists, addressing whether these were depressed patients with comorbid heart failure or patients with heart failure and comorbid depression. We ended up agreeing that since these patients mostly die from heart failure, therefore this is the main disease. And since there was no evidence from other cardiovascular studies that antidepressants were of use, we were allowed to do the study,” she explained.

The trial was halted early for futility at the request of the data safety monitoring board after a median of 18 months. At that point, the primary composite endpoint of death or unplanned hospitalization had occurred in 116 patients in the escitalopram group and 119 on placebo.

A key secondary endpoint – improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) at 12 weeks – was also a virtual dead heat. From a baseline score of 21, both the escitalopram and placebo groups showed a clinically meaningful improvement of roughly 9 points. The improvement in MADRS scores in the control group piqued investigators’ interest because no psychotherapy or counseling was involved in the trial.

The target dose of escitalopram was 20 mg/day, with uptitration to that goal taking place over the first 12 weeks. The mean dose of the antidepressant at week 12 was 13.7 mg/day. During the course of the study, however, the target dose dropped to 10 mg/day in patients over age 65 in accordance with updated regulatory guidance regarding possible proarrhythmic QTc prolongation in older patients. As it turned out, QTc prolongation was not an issue in MOOD-HF. Indeed, there was no difference between the two groups in terms of any serious adverse events. Adherence to the study medication was good, Dr. Angermann continued.

While the dose of escitalopram was being uptitrated during the first 12 weeks, so was guideline-directed medical therapy for heart failure in both study arms. The patients improved from being at 56% of the recommended dose of ACE inhibitor/angiotensin receptor blocker therapy at baseline to 64%, and from 58% of the target dose of beta-blocker therapy to 63%. That, rather than the antidepressant, appeared to be responsible for the improvement in heart failure, she said.

Both study arms showed similar improvements over time in New York Heart Association functional class and left ventricular ejection fraction. But levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) – an important biomarker of heart failure severity – improved only in the placebo-treated controls. The same held true for reduction in left ventricular end diastolic diameter.

“This suggests a somewhat attenuated improvement in heart failure in the escitalopram group,” the cardiologist observed.

The investigators conducted a post hoc analysis to generate a hypothesis-generating risk score for the primary outcome. One point each was given for age greater than 62.6 years, a baseline NT-proBNP level in excess of 807 ng/L, a heart rate greater than 68 bpm, being New York Heart Association class III/IV, and having a left ventricular end diastolic diameter in excess of 59 mm. These were thresholds that identified patients in the top half of the study population for each of these variables.

In patients with a risk score of 0-2, escitalopram was associated with a highly significant 33% reduction in the risk of death or unplanned hospitalization compared with placebo. However, in patients with a score of 3-5, the escitalopram group had a 52% greater risk of the primary endpoint than controls.

“This suggests a heterogeneous pathophysiology and an impact of individual disease profiles on the effects of the study medication,” Dr. Angermann said.

MOOD-HF was funded chiefly by the German Ministry of Education and Research and the University of Wurzburg. Lundbeck provided the escitalopram gratis. Dr. Angermann reported serving as a consultant to ResMed, Novartis, and Vifor and receiving research grants from Lundbeck, Alere, and Boehringer Ingelheim.

bjancin@frontlinemedcom.com

SAN DIEGO – Patients with major depressive disorder and heart failure with reduced ejection fraction fared no better with a selective serotonin reuptake inhibitor than with placebo in terms of heart failure outcomes or improved psychological well being in MOOD-HF, the first large randomized trial to examine the issue.

“MOOD-HF does not provide a rationale for the use of escitalopram in patients with systolic heart failure and comorbid depression. MOOD-HF suggests, however, that optimal heart failure management resulting in improved signs and symptoms might possibly be a means to ameliorate comorbid depression,” Dr. Christiane E. Angermann said at the annual meeting of the American College of Cardiology.

Moreover, exploratory secondary analysis suggested “a very subtle long-term effect of the antidepressant that may not be so favorable” in patients with more severe heart failure, she added.

“It seems that some of our patients take antidepressants in vain, and we should care more about the heart failure medications,” said Dr. Angermann, chairman of the MOOD-HF trial and director of clinical research at the Comprehensive Heart Failure Center at the University of Wurzburg (Germany).

MOOD-HF was an ambitious clinical trial conducted at 16 German academic medical centers. The study began with the screening – via the Patient Health Questionnaire–9 – of more than 11,000 patients who had heart failure with reduced ejection fraction. A psychiatrist using the Structured Clinical Interview for Depression eventually diagnosed a subgroup as having major depressive disorder. Ultimately, 372 patients with an average left ventricular ejection fraction of 35% were randomized in double-blind fashion to escitalopram (Lexapro) or placebo for a planned 24 months.

The study rationale stemmed from the well-established finding that depression is three to five times more common in heart failure patients than in the general population, and that the severity of depression in these patients shows a dose-response relationship with their risks of all-cause mortality and heart failure hospitalization. The primary study hypothesis in MOOD-HF was that treating the comorbid depression would result in a reduced risk of all-cause mortality and unplanned hospitalization for any cause.

“Never before had an ethics committee been persuaded to allow patients with major depressive disorder to be on a placebo for 2 years,” said Dr. Angermann. “It took a lot of discussion with the psychiatrists, addressing whether these were depressed patients with comorbid heart failure or patients with heart failure and comorbid depression. We ended up agreeing that since these patients mostly die from heart failure, therefore this is the main disease. And since there was no evidence from other cardiovascular studies that antidepressants were of use, we were allowed to do the study,” she explained.

The trial was halted early for futility at the request of the data safety monitoring board after a median of 18 months. At that point, the primary composite endpoint of death or unplanned hospitalization had occurred in 116 patients in the escitalopram group and 119 on placebo.

A key secondary endpoint – improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) at 12 weeks – was also a virtual dead heat. From a baseline score of 21, both the escitalopram and placebo groups showed a clinically meaningful improvement of roughly 9 points. The improvement in MADRS scores in the control group piqued investigators’ interest because no psychotherapy or counseling was involved in the trial.

The target dose of escitalopram was 20 mg/day, with uptitration to that goal taking place over the first 12 weeks. The mean dose of the antidepressant at week 12 was 13.7 mg/day. During the course of the study, however, the target dose dropped to 10 mg/day in patients over age 65 in accordance with updated regulatory guidance regarding possible proarrhythmic QTc prolongation in older patients. As it turned out, QTc prolongation was not an issue in MOOD-HF. Indeed, there was no difference between the two groups in terms of any serious adverse events. Adherence to the study medication was good, Dr. Angermann continued.

While the dose of escitalopram was being uptitrated during the first 12 weeks, so was guideline-directed medical therapy for heart failure in both study arms. The patients improved from being at 56% of the recommended dose of ACE inhibitor/angiotensin receptor blocker therapy at baseline to 64%, and from 58% of the target dose of beta-blocker therapy to 63%. That, rather than the antidepressant, appeared to be responsible for the improvement in heart failure, she said.

Both study arms showed similar improvements over time in New York Heart Association functional class and left ventricular ejection fraction. But levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) – an important biomarker of heart failure severity – improved only in the placebo-treated controls. The same held true for reduction in left ventricular end diastolic diameter.

“This suggests a somewhat attenuated improvement in heart failure in the escitalopram group,” the cardiologist observed.

The investigators conducted a post hoc analysis to generate a hypothesis-generating risk score for the primary outcome. One point each was given for age greater than 62.6 years, a baseline NT-proBNP level in excess of 807 ng/L, a heart rate greater than 68 bpm, being New York Heart Association class III/IV, and having a left ventricular end diastolic diameter in excess of 59 mm. These were thresholds that identified patients in the top half of the study population for each of these variables.

In patients with a risk score of 0-2, escitalopram was associated with a highly significant 33% reduction in the risk of death or unplanned hospitalization compared with placebo. However, in patients with a score of 3-5, the escitalopram group had a 52% greater risk of the primary endpoint than controls.

“This suggests a heterogeneous pathophysiology and an impact of individual disease profiles on the effects of the study medication,” Dr. Angermann said.

MOOD-HF was funded chiefly by the German Ministry of Education and Research and the University of Wurzburg. Lundbeck provided the escitalopram gratis. Dr. Angermann reported serving as a consultant to ResMed, Novartis, and Vifor and receiving research grants from Lundbeck, Alere, and Boehringer Ingelheim.

bjancin@frontlinemedcom.com

SAN DIEGO – Patients with major depressive disorder and heart failure with reduced ejection fraction fared no better with a selective serotonin reuptake inhibitor than with placebo in terms of heart failure outcomes or improved psychological well being in MOOD-HF, the first large randomized trial to examine the issue.

“MOOD-HF does not provide a rationale for the use of escitalopram in patients with systolic heart failure and comorbid depression. MOOD-HF suggests, however, that optimal heart failure management resulting in improved signs and symptoms might possibly be a means to ameliorate comorbid depression,” Dr. Christiane E. Angermann said at the annual meeting of the American College of Cardiology.

Moreover, exploratory secondary analysis suggested “a very subtle long-term effect of the antidepressant that may not be so favorable” in patients with more severe heart failure, she added.

“It seems that some of our patients take antidepressants in vain, and we should care more about the heart failure medications,” said Dr. Angermann, chairman of the MOOD-HF trial and director of clinical research at the Comprehensive Heart Failure Center at the University of Wurzburg (Germany).

MOOD-HF was an ambitious clinical trial conducted at 16 German academic medical centers. The study began with the screening – via the Patient Health Questionnaire–9 – of more than 11,000 patients who had heart failure with reduced ejection fraction. A psychiatrist using the Structured Clinical Interview for Depression eventually diagnosed a subgroup as having major depressive disorder. Ultimately, 372 patients with an average left ventricular ejection fraction of 35% were randomized in double-blind fashion to escitalopram (Lexapro) or placebo for a planned 24 months.

The study rationale stemmed from the well-established finding that depression is three to five times more common in heart failure patients than in the general population, and that the severity of depression in these patients shows a dose-response relationship with their risks of all-cause mortality and heart failure hospitalization. The primary study hypothesis in MOOD-HF was that treating the comorbid depression would result in a reduced risk of all-cause mortality and unplanned hospitalization for any cause.

“Never before had an ethics committee been persuaded to allow patients with major depressive disorder to be on a placebo for 2 years,” said Dr. Angermann. “It took a lot of discussion with the psychiatrists, addressing whether these were depressed patients with comorbid heart failure or patients with heart failure and comorbid depression. We ended up agreeing that since these patients mostly die from heart failure, therefore this is the main disease. And since there was no evidence from other cardiovascular studies that antidepressants were of use, we were allowed to do the study,” she explained.

The trial was halted early for futility at the request of the data safety monitoring board after a median of 18 months. At that point, the primary composite endpoint of death or unplanned hospitalization had occurred in 116 patients in the escitalopram group and 119 on placebo.

A key secondary endpoint – improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) at 12 weeks – was also a virtual dead heat. From a baseline score of 21, both the escitalopram and placebo groups showed a clinically meaningful improvement of roughly 9 points. The improvement in MADRS scores in the control group piqued investigators’ interest because no psychotherapy or counseling was involved in the trial.

The target dose of escitalopram was 20 mg/day, with uptitration to that goal taking place over the first 12 weeks. The mean dose of the antidepressant at week 12 was 13.7 mg/day. During the course of the study, however, the target dose dropped to 10 mg/day in patients over age 65 in accordance with updated regulatory guidance regarding possible proarrhythmic QTc prolongation in older patients. As it turned out, QTc prolongation was not an issue in MOOD-HF. Indeed, there was no difference between the two groups in terms of any serious adverse events. Adherence to the study medication was good, Dr. Angermann continued.

While the dose of escitalopram was being uptitrated during the first 12 weeks, so was guideline-directed medical therapy for heart failure in both study arms. The patients improved from being at 56% of the recommended dose of ACE inhibitor/angiotensin receptor blocker therapy at baseline to 64%, and from 58% of the target dose of beta-blocker therapy to 63%. That, rather than the antidepressant, appeared to be responsible for the improvement in heart failure, she said.

Both study arms showed similar improvements over time in New York Heart Association functional class and left ventricular ejection fraction. But levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) – an important biomarker of heart failure severity – improved only in the placebo-treated controls. The same held true for reduction in left ventricular end diastolic diameter.

“This suggests a somewhat attenuated improvement in heart failure in the escitalopram group,” the cardiologist observed.

The investigators conducted a post hoc analysis to generate a hypothesis-generating risk score for the primary outcome. One point each was given for age greater than 62.6 years, a baseline NT-proBNP level in excess of 807 ng/L, a heart rate greater than 68 bpm, being New York Heart Association class III/IV, and having a left ventricular end diastolic diameter in excess of 59 mm. These were thresholds that identified patients in the top half of the study population for each of these variables.

In patients with a risk score of 0-2, escitalopram was associated with a highly significant 33% reduction in the risk of death or unplanned hospitalization compared with placebo. However, in patients with a score of 3-5, the escitalopram group had a 52% greater risk of the primary endpoint than controls.

“This suggests a heterogeneous pathophysiology and an impact of individual disease profiles on the effects of the study medication,” Dr. Angermann said.

MOOD-HF was funded chiefly by the German Ministry of Education and Research and the University of Wurzburg. Lundbeck provided the escitalopram gratis. Dr. Angermann reported serving as a consultant to ResMed, Novartis, and Vifor and receiving research grants from Lundbeck, Alere, and Boehringer Ingelheim.

bjancin@frontlinemedcom.com

SAN DIEGO – Percutaneous pulmonary artery denervation for the treatment of pulmonary arterial hypertension safely resulted in significantly greater improvement in functional capacity and hemodynamics compared with medication, in a controlled before-and-after study.

A particularly noteworthy secondary finding in the study was that rehospitalizations during the first 6 months after pulmonary artery denervation (PADN) occurred just one-third as frequently as in the 6-month preprocedural period on standard medications, Dr. Shao-Liang Chen said at the annual meeting of the American College of Cardiology.

He and his coinvestigators, including Dr. Gregg W. Stone of Columbia University in New York, developed a percutaneous catheter-based method of destroying the pulmonary baroreceptor structure located at the bifurcation area of the middle pulmonary artery. Along the way, they redefined the understanding of the pathogenesis of pulmonary artery hypertension (PAH) by demonstrating that local sympathetic nerve activity plays a pivotal role in modulating the elevations of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR), which are the disease hallmarks.

Dr. Chen and coinvestigators previously reported the first-in-man study of PADN, which demonstrated safety and short-term efficacy (J. Am. Coll. Cardiol. 2013;62:1092-100). At ACC 15, Dr. Chen presented the findings of the new PADN-2 study, which expands upon the first study by including more patients and longer and more comprehensive follow-up.

The study comprised 28 patients with PAH, including 11 with idiopathic PAH and 8 with pulmonary hypertension caused by left ventricular disease. All of them underwent medication washout followed by right heart catheterization and echocardiography for baseline off-drug hemodynamic measurements as well as a 6-minute walk distance test of their functional capacity. Then they went back on medications for 6 months, after which they underwent repeat testing. Then their medications were discontinued and they underwent PADN. Six months after the procedure, still off medications, they were retested once again.

The primary study endpoint was change in 6-minute walk distance. After 6 months of medication it improved from 361 to 373 meters, a modest 3.9% gain over off-drug baseline. In contrast, 6-minute walk distance grew from 358 to 423 meters 6 months after PADN, a clinically important 23.9% improvement, reported Dr. Chen, a cardiologist at First Hospital of Nanjing (China) Medical University.

Multiple secondary hemodynamic endpoints also showed significantly greater improvement with PADN than medical therapy.

Twelve predefined clinical events – mostly involving worsening PAH – occurred during medical management, compared with three in the 6 months following PADN.

In addition, there were 12 hospitalizations during the 6 months on medical management compared with only 4 after the same patients underwent PADN. Health care costs averaged $35,000 per patient during the 6-month study period on medication compared with $6,000 per patient in the first 6 months after PADN.

There were no deaths, aneurysms, access site hematomas, or thrombotic events during either study period.

Further randomized, controlled trials are planned to explore the possibility that the benefits seen in the PADN-2 trial will result in reduced mortality in patients with PAH, according to Dr. Chen.

The PADN-2 trial was sponsored by Nanjing Medical University. Dr. Chen reported serving as a consultant to MicroPort.

bjancin@frontlinemedcom.com

SAN DIEGO – Percutaneous pulmonary artery denervation for the treatment of pulmonary arterial hypertension safely resulted in significantly greater improvement in functional capacity and hemodynamics compared with medication, in a controlled before-and-after study.

A particularly noteworthy secondary finding in the study was that rehospitalizations during the first 6 months after pulmonary artery denervation (PADN) occurred just one-third as frequently as in the 6-month preprocedural period on standard medications, Dr. Shao-Liang Chen said at the annual meeting of the American College of Cardiology.

He and his coinvestigators, including Dr. Gregg W. Stone of Columbia University in New York, developed a percutaneous catheter-based method of destroying the pulmonary baroreceptor structure located at the bifurcation area of the middle pulmonary artery. Along the way, they redefined the understanding of the pathogenesis of pulmonary artery hypertension (PAH) by demonstrating that local sympathetic nerve activity plays a pivotal role in modulating the elevations of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR), which are the disease hallmarks.

Dr. Chen and coinvestigators previously reported the first-in-man study of PADN, which demonstrated safety and short-term efficacy (J. Am. Coll. Cardiol. 2013;62:1092-100). At ACC 15, Dr. Chen presented the findings of the new PADN-2 study, which expands upon the first study by including more patients and longer and more comprehensive follow-up.

The study comprised 28 patients with PAH, including 11 with idiopathic PAH and 8 with pulmonary hypertension caused by left ventricular disease. All of them underwent medication washout followed by right heart catheterization and echocardiography for baseline off-drug hemodynamic measurements as well as a 6-minute walk distance test of their functional capacity. Then they went back on medications for 6 months, after which they underwent repeat testing. Then their medications were discontinued and they underwent PADN. Six months after the procedure, still off medications, they were retested once again.

The primary study endpoint was change in 6-minute walk distance. After 6 months of medication it improved from 361 to 373 meters, a modest 3.9% gain over off-drug baseline. In contrast, 6-minute walk distance grew from 358 to 423 meters 6 months after PADN, a clinically important 23.9% improvement, reported Dr. Chen, a cardiologist at First Hospital of Nanjing (China) Medical University.

Multiple secondary hemodynamic endpoints also showed significantly greater improvement with PADN than medical therapy.

Twelve predefined clinical events – mostly involving worsening PAH – occurred during medical management, compared with three in the 6 months following PADN.

In addition, there were 12 hospitalizations during the 6 months on medical management compared with only 4 after the same patients underwent PADN. Health care costs averaged $35,000 per patient during the 6-month study period on medication compared with $6,000 per patient in the first 6 months after PADN.

There were no deaths, aneurysms, access site hematomas, or thrombotic events during either study period.

Further randomized, controlled trials are planned to explore the possibility that the benefits seen in the PADN-2 trial will result in reduced mortality in patients with PAH, according to Dr. Chen.

The PADN-2 trial was sponsored by Nanjing Medical University. Dr. Chen reported serving as a consultant to MicroPort.

bjancin@frontlinemedcom.com

SAN DIEGO – Percutaneous pulmonary artery denervation for the treatment of pulmonary arterial hypertension safely resulted in significantly greater improvement in functional capacity and hemodynamics compared with medication, in a controlled before-and-after study.

A particularly noteworthy secondary finding in the study was that rehospitalizations during the first 6 months after pulmonary artery denervation (PADN) occurred just one-third as frequently as in the 6-month preprocedural period on standard medications, Dr. Shao-Liang Chen said at the annual meeting of the American College of Cardiology.

He and his coinvestigators, including Dr. Gregg W. Stone of Columbia University in New York, developed a percutaneous catheter-based method of destroying the pulmonary baroreceptor structure located at the bifurcation area of the middle pulmonary artery. Along the way, they redefined the understanding of the pathogenesis of pulmonary artery hypertension (PAH) by demonstrating that local sympathetic nerve activity plays a pivotal role in modulating the elevations of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR), which are the disease hallmarks.

Dr. Chen and coinvestigators previously reported the first-in-man study of PADN, which demonstrated safety and short-term efficacy (J. Am. Coll. Cardiol. 2013;62:1092-100). At ACC 15, Dr. Chen presented the findings of the new PADN-2 study, which expands upon the first study by including more patients and longer and more comprehensive follow-up.

The study comprised 28 patients with PAH, including 11 with idiopathic PAH and 8 with pulmonary hypertension caused by left ventricular disease. All of them underwent medication washout followed by right heart catheterization and echocardiography for baseline off-drug hemodynamic measurements as well as a 6-minute walk distance test of their functional capacity. Then they went back on medications for 6 months, after which they underwent repeat testing. Then their medications were discontinued and they underwent PADN. Six months after the procedure, still off medications, they were retested once again.

The primary study endpoint was change in 6-minute walk distance. After 6 months of medication it improved from 361 to 373 meters, a modest 3.9% gain over off-drug baseline. In contrast, 6-minute walk distance grew from 358 to 423 meters 6 months after PADN, a clinically important 23.9% improvement, reported Dr. Chen, a cardiologist at First Hospital of Nanjing (China) Medical University.

Multiple secondary hemodynamic endpoints also showed significantly greater improvement with PADN than medical therapy.

Twelve predefined clinical events – mostly involving worsening PAH – occurred during medical management, compared with three in the 6 months following PADN.

In addition, there were 12 hospitalizations during the 6 months on medical management compared with only 4 after the same patients underwent PADN. Health care costs averaged $35,000 per patient during the 6-month study period on medication compared with $6,000 per patient in the first 6 months after PADN.

There were no deaths, aneurysms, access site hematomas, or thrombotic events during either study period.

Further randomized, controlled trials are planned to explore the possibility that the benefits seen in the PADN-2 trial will result in reduced mortality in patients with PAH, according to Dr. Chen.

The PADN-2 trial was sponsored by Nanjing Medical University. Dr. Chen reported serving as a consultant to MicroPort.

bjancin@frontlinemedcom.com

SAN DIEGO– Bendavia, a novel agent designed to prevent reperfusion injury by improving myocardial energetics, failed to reduce infarct size in ST-elevation MI patients in a phase II randomized trial.

Despite this disappointing result on the primary study endpoint, there was a silver lining. The study, known as the EMBRACE STEMI trial, generated two provocative findings in exploratory, hypothesis-generating secondary analyses: Bendavia appeared to reduce new-onset symptomatic heart failure early on after percutaneous coronary intervention, and the drug also had an apparent renal protective effect, Dr. C. Michael Gibson reported at the annual meeting of the American College of Cardiology.

These two potentially important findings are being studied more fully in three ongoing prospective, randomized, double-blind, placebo-controlled trials, added Dr. Gibson, professor of medicine at Harvard Medical School, Boston, and chairman of EMBRACE STEMI (Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events).

As for the negative result in terms of the primary study hypothesis that Bendavia would reduce infarct size by preventing reperfusion injury in patients undergoing PCI for large STEMIs, as it had done successfully in animal models, the cardiologist said all indications are that the investigators targeted the right patients at the right time with the right dose of the medication.

“I think we conducted the experiment in such a way that if there was a ‘there’ there, we were going to see it,” Dr. Gibson said.

EMBRACE STEMI included 118 patients with large, first-time, anterior MIs featuring proximal or mid-left anterior descending coronary artery lesions. To be eligible for the study, patients had to arrive at the catheterization lab with a closed artery within 4 hours after symptom onset. They were then randomized in double-blind fashion to intravenous Bendavia at 0.05 mg/kg per hour for 1 hour beginning 15 minutes before PCI or to an equal volume of placebo.

The study, conducted by the PERFUSE study group at 24 sites in the United States and three European countries, was planned to be considerably larger, but to the surprise of investigators, 40% of patients arrived at the cath lab with an open artery.

“This is higher than the historical figure of 20%,” Dr. Gibson noted. “I think this is one of the notable findings in this study: Whether due to earlier presentation or better pharmacotherapy, it’s tougher to locate people with closed arteries for these kinds of studies in 2015.”

Bendavia did not significantly reduce infarct size as measured by the areas under the curve for creatine kinase MB (CK-MB) or troponin I over the initial 72 hours after PCI. Moreover, cardiac MRIs obtained at 4 and 30 days post PCI showed no significant difference between the Bendavia and placebo groups in infarct volume, left ventricular mass, edema volume, or left ventricular ejection fraction. Rates of ST-segment resolution immediately and 24 hours post PCI did not differ between the two groups, either. Nor did TIMI flow grade, frame count, or myocardial perfusion grade. Also, 30-day and 6-month rates of the composite clinical endpoint of death, new-onset heart failure beginning more than 24 hours post PCI, and heart failure rehospitalization did not differ in the Bendavia and control groups.

However, the incidence of new-onset heart failure within the first 8 hours post PCI was 8.6% in the Bendavia group compared with 18.3% in controls. This finding has prompted the two ongoing randomized trials where Bendavia is being tested in higher doses in patients with stable heart failure with reduced ejection fraction.

Bendavia is a peptide targeting the mitochondria, where it binds with cardiolipin and preserves the integrity of the electron transport system. In animal models of heart failure, it improves left ventricular function.

“It’s not an inotrope. It doesn’t change heart rate or blood pressure. Rather than increasing demands on the heart, it offers a supply side solution in improving myocardial energetics,” Dr. Gibson explained.

Bendavia was associated with renal preservation as reflected in a significantly smaller increase in creatinine level in the first 12 hours post PCI: 1.0 mcmol/L compared with 3.7 mcmol/L in controls.

This finding piqued the interest of discussant Dr. James B. McClurken, professor and vice chair of surgery at Temple University in Philadelphia.

“The renal protective findings have widespread potential application, including for coronary artery bypass surgery patients. What are your thoughts about the mechanism?” he asked.

Dr. Gibson replied that a small study done at the Mayo Clinic suggests a biologically plausible mechanism: Bendavia dramatically improved kidney hypoxia secondary to ischemia and the dye load entailed in longer PCI procedures.

Dr. Gibson reported receiving a research grant from Stealth BioTherapeutics to conduct the EMBRACE STEMI trial. He serves as a consultant to numerous pharmaceutical and medical device companies.

bjancin@frontlinemedcom.com

SAN DIEGO– Bendavia, a novel agent designed to prevent reperfusion injury by improving myocardial energetics, failed to reduce infarct size in ST-elevation MI patients in a phase II randomized trial.

Despite this disappointing result on the primary study endpoint, there was a silver lining. The study, known as the EMBRACE STEMI trial, generated two provocative findings in exploratory, hypothesis-generating secondary analyses: Bendavia appeared to reduce new-onset symptomatic heart failure early on after percutaneous coronary intervention, and the drug also had an apparent renal protective effect, Dr. C. Michael Gibson reported at the annual meeting of the American College of Cardiology.

These two potentially important findings are being studied more fully in three ongoing prospective, randomized, double-blind, placebo-controlled trials, added Dr. Gibson, professor of medicine at Harvard Medical School, Boston, and chairman of EMBRACE STEMI (Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events).

As for the negative result in terms of the primary study hypothesis that Bendavia would reduce infarct size by preventing reperfusion injury in patients undergoing PCI for large STEMIs, as it had done successfully in animal models, the cardiologist said all indications are that the investigators targeted the right patients at the right time with the right dose of the medication.

“I think we conducted the experiment in such a way that if there was a ‘there’ there, we were going to see it,” Dr. Gibson said.

EMBRACE STEMI included 118 patients with large, first-time, anterior MIs featuring proximal or mid-left anterior descending coronary artery lesions. To be eligible for the study, patients had to arrive at the catheterization lab with a closed artery within 4 hours after symptom onset. They were then randomized in double-blind fashion to intravenous Bendavia at 0.05 mg/kg per hour for 1 hour beginning 15 minutes before PCI or to an equal volume of placebo.

The study, conducted by the PERFUSE study group at 24 sites in the United States and three European countries, was planned to be considerably larger, but to the surprise of investigators, 40% of patients arrived at the cath lab with an open artery.

“This is higher than the historical figure of 20%,” Dr. Gibson noted. “I think this is one of the notable findings in this study: Whether due to earlier presentation or better pharmacotherapy, it’s tougher to locate people with closed arteries for these kinds of studies in 2015.”

Bendavia did not significantly reduce infarct size as measured by the areas under the curve for creatine kinase MB (CK-MB) or troponin I over the initial 72 hours after PCI. Moreover, cardiac MRIs obtained at 4 and 30 days post PCI showed no significant difference between the Bendavia and placebo groups in infarct volume, left ventricular mass, edema volume, or left ventricular ejection fraction. Rates of ST-segment resolution immediately and 24 hours post PCI did not differ between the two groups, either. Nor did TIMI flow grade, frame count, or myocardial perfusion grade. Also, 30-day and 6-month rates of the composite clinical endpoint of death, new-onset heart failure beginning more than 24 hours post PCI, and heart failure rehospitalization did not differ in the Bendavia and control groups.

However, the incidence of new-onset heart failure within the first 8 hours post PCI was 8.6% in the Bendavia group compared with 18.3% in controls. This finding has prompted the two ongoing randomized trials where Bendavia is being tested in higher doses in patients with stable heart failure with reduced ejection fraction.

Bendavia is a peptide targeting the mitochondria, where it binds with cardiolipin and preserves the integrity of the electron transport system. In animal models of heart failure, it improves left ventricular function.

“It’s not an inotrope. It doesn’t change heart rate or blood pressure. Rather than increasing demands on the heart, it offers a supply side solution in improving myocardial energetics,” Dr. Gibson explained.

Bendavia was associated with renal preservation as reflected in a significantly smaller increase in creatinine level in the first 12 hours post PCI: 1.0 mcmol/L compared with 3.7 mcmol/L in controls.

This finding piqued the interest of discussant Dr. James B. McClurken, professor and vice chair of surgery at Temple University in Philadelphia.

“The renal protective findings have widespread potential application, including for coronary artery bypass surgery patients. What are your thoughts about the mechanism?” he asked.

Dr. Gibson replied that a small study done at the Mayo Clinic suggests a biologically plausible mechanism: Bendavia dramatically improved kidney hypoxia secondary to ischemia and the dye load entailed in longer PCI procedures.

Dr. Gibson reported receiving a research grant from Stealth BioTherapeutics to conduct the EMBRACE STEMI trial. He serves as a consultant to numerous pharmaceutical and medical device companies.

bjancin@frontlinemedcom.com

SAN DIEGO– Bendavia, a novel agent designed to prevent reperfusion injury by improving myocardial energetics, failed to reduce infarct size in ST-elevation MI patients in a phase II randomized trial.

Despite this disappointing result on the primary study endpoint, there was a silver lining. The study, known as the EMBRACE STEMI trial, generated two provocative findings in exploratory, hypothesis-generating secondary analyses: Bendavia appeared to reduce new-onset symptomatic heart failure early on after percutaneous coronary intervention, and the drug also had an apparent renal protective effect, Dr. C. Michael Gibson reported at the annual meeting of the American College of Cardiology.

These two potentially important findings are being studied more fully in three ongoing prospective, randomized, double-blind, placebo-controlled trials, added Dr. Gibson, professor of medicine at Harvard Medical School, Boston, and chairman of EMBRACE STEMI (Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events).

As for the negative result in terms of the primary study hypothesis that Bendavia would reduce infarct size by preventing reperfusion injury in patients undergoing PCI for large STEMIs, as it had done successfully in animal models, the cardiologist said all indications are that the investigators targeted the right patients at the right time with the right dose of the medication.

“I think we conducted the experiment in such a way that if there was a ‘there’ there, we were going to see it,” Dr. Gibson said.

EMBRACE STEMI included 118 patients with large, first-time, anterior MIs featuring proximal or mid-left anterior descending coronary artery lesions. To be eligible for the study, patients had to arrive at the catheterization lab with a closed artery within 4 hours after symptom onset. They were then randomized in double-blind fashion to intravenous Bendavia at 0.05 mg/kg per hour for 1 hour beginning 15 minutes before PCI or to an equal volume of placebo.

The study, conducted by the PERFUSE study group at 24 sites in the United States and three European countries, was planned to be considerably larger, but to the surprise of investigators, 40% of patients arrived at the cath lab with an open artery.

“This is higher than the historical figure of 20%,” Dr. Gibson noted. “I think this is one of the notable findings in this study: Whether due to earlier presentation or better pharmacotherapy, it’s tougher to locate people with closed arteries for these kinds of studies in 2015.”

Bendavia did not significantly reduce infarct size as measured by the areas under the curve for creatine kinase MB (CK-MB) or troponin I over the initial 72 hours after PCI. Moreover, cardiac MRIs obtained at 4 and 30 days post PCI showed no significant difference between the Bendavia and placebo groups in infarct volume, left ventricular mass, edema volume, or left ventricular ejection fraction. Rates of ST-segment resolution immediately and 24 hours post PCI did not differ between the two groups, either. Nor did TIMI flow grade, frame count, or myocardial perfusion grade. Also, 30-day and 6-month rates of the composite clinical endpoint of death, new-onset heart failure beginning more than 24 hours post PCI, and heart failure rehospitalization did not differ in the Bendavia and control groups.

However, the incidence of new-onset heart failure within the first 8 hours post PCI was 8.6% in the Bendavia group compared with 18.3% in controls. This finding has prompted the two ongoing randomized trials where Bendavia is being tested in higher doses in patients with stable heart failure with reduced ejection fraction.

Bendavia is a peptide targeting the mitochondria, where it binds with cardiolipin and preserves the integrity of the electron transport system. In animal models of heart failure, it improves left ventricular function.

“It’s not an inotrope. It doesn’t change heart rate or blood pressure. Rather than increasing demands on the heart, it offers a supply side solution in improving myocardial energetics,” Dr. Gibson explained.

Bendavia was associated with renal preservation as reflected in a significantly smaller increase in creatinine level in the first 12 hours post PCI: 1.0 mcmol/L compared with 3.7 mcmol/L in controls.

This finding piqued the interest of discussant Dr. James B. McClurken, professor and vice chair of surgery at Temple University in Philadelphia.

“The renal protective findings have widespread potential application, including for coronary artery bypass surgery patients. What are your thoughts about the mechanism?” he asked.

Dr. Gibson replied that a small study done at the Mayo Clinic suggests a biologically plausible mechanism: Bendavia dramatically improved kidney hypoxia secondary to ischemia and the dye load entailed in longer PCI procedures.

Dr. Gibson reported receiving a research grant from Stealth BioTherapeutics to conduct the EMBRACE STEMI trial. He serves as a consultant to numerous pharmaceutical and medical device companies.

bjancin@frontlinemedcom.com

SAN DIEGO– Baroreflex activation therapy showed promise as an important new device therapy for patients with New York Heart Association Class III heart failure, according to researchers.

In a preliminary randomized trial, the investigational therapy demonstrated safety comparable to that of established device therapies for heart failure. And it significantly improved functional status, exercise capacity, and quality of life while reducing levels of the biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) and days-in-hospital for worsening heart failure, Dr. William T. Abraham said at the annual meeting of the American College of Cardiology.

“The trial showed important results,” he said. “If these observations are confirmed in larger studies, baroreflex activation therapy may offer a new addition for the treatment of advanced heart failure patients with a reduced left ventricular ejection fraction.”

Novel therapies for patients with NYHA class III heart failure with a reduced ejection fraction (HFrEF) are sorely needed, he added, as 25%-35% of patients with HFrEF remain in NYHA class III despite current drug and device therapies. These patients are moderately symptomatic, meaning they are sick enough that their quality of life is sharply diminished, but not sufficiently ill to qualify for advanced heart therapies, such as cardiac transplantation or a left ventricular assist device.

Dr. Abraham presented the findings of a multinational, prospective, randomized, 6-month, controlled trial involving 140 NYHA class III HFrEF patients in the United States, Canada, Germany, and France. They were randomized to optimal guideline-directed medical therapy alone or in conjunction with baroreflex activation therapy (BAT), a form of neuromodulatory therapy involving electrical stimulation of the carotid baroreflex baroreceptor delivered by an implanted device similar to a pacemaker.

Progressive heart failure is characterized by increased sympathetic and reduced parasympathetic nerve activity. BAT addresses both abnormalities.

“This form of neuromodulation differs from other forms of neuromodulation in that it does not target a peripheral efferent nerve, but rather it targets the carotid baroreceptor. It targets afferent signals to the brain, which then produce an integrated autonomic nervous system response resulting in inhibition of sympathetic activity and enhancement of parasympathetic activity. So this is a physiologic form of autonomic rebalancing that is mediated via the CNS,” explained Dr. Abraham, professor of medicine and director of the division of cardiovascular medicine at Ohio State University, Columbus.

The primary safety endpoint was freedom from system- and procedure-related major adverse neurologic and cardiovascular events at 6 months. The rate was 97.2%. There were no deaths, and complications – all of which occurred within the first 7 days – were few and short lived, with rates similar to those seen with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT). The BAT device, known as the CVRx Barostim neo, did not interact with the ICDs and CRT devices present in a large number of participants. No hypotension occurred in this normotensive HFrEF population.

To place the efficacy outcomes in perspective, Dr. Abraham continued, it’s worth noting that the average 19.5-point between-group difference favoring BAT in scores on the Minnesota Living with Heart Failure Quality of Life Questionnaire (MLHFQ) at 6 months compared to a baseline of 45 points dwarfs the benefits obtainable with standard therapies.

“Please remember that our best drug therapies for HFrEF – ACE inhibitors and beta blockers– improve the MLHFQ score by 4 or 5 points, and cardiac resynchronization therapy improves that score by an average of 9 or 10 points,” he said. From a baseline of 300 meters, the 6-minute hall walk distance improved by 58 meters more in the BAT group than in controls. By comparison, CRT improves the distance walked in 6 minutes by about 30 meters.

“The magnitude of benefit of BAT exceeds that seen with standard therapies, it was seen on top of those standard therapies, and it certainly falls into a range that would be considered clinically meaningful,” the cardiologist asserted.

Left ventricular ejection fraction improved in the BAT group by an average of 2.4% from a baseline of 24% while decreasing by 0.1% in controls. The between-group difference in NT-proBNP at 6 months was 342 pg/mL in favor of the BAT group, starting from a baseline level of roughly 1,300 pg/mL.

The BAT group averaged 6.95 hospital days per year for worsening heart failure during the 6 months prior to enrollment and 0.67 days per year in the 6 months following device activation, for an adjusted 82% relative risk reduction. In contrast, hospital days for heart failure remained steady in controls. The possibility of a new treatment that reduces heart failure hospitalizations is of particular interest in light of the enormous financial burden such hospitalizations currently place upon the Medicare system.

Simultaneously with Dr. Abraham’s presentation at ACC 15, the study manuscript was published online (JACC: Heart Failure 2015 [doi: 10.1016/j.jchf.2015.02.006]).

Dr. Abraham is a consultant to CVRx (which funded the study), as well as Novartis, St. Jude Medical, CardioMEMS, and Abbott Vascular. 

bjancin@frontlinemedcom.com

SAN DIEGO– Baroreflex activation therapy showed promise as an important new device therapy for patients with New York Heart Association Class III heart failure, according to researchers.

In a preliminary randomized trial, the investigational therapy demonstrated safety comparable to that of established device therapies for heart failure. And it significantly improved functional status, exercise capacity, and quality of life while reducing levels of the biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) and days-in-hospital for worsening heart failure, Dr. William T. Abraham said at the annual meeting of the American College of Cardiology.

“The trial showed important results,” he said. “If these observations are confirmed in larger studies, baroreflex activation therapy may offer a new addition for the treatment of advanced heart failure patients with a reduced left ventricular ejection fraction.”

Novel therapies for patients with NYHA class III heart failure with a reduced ejection fraction (HFrEF) are sorely needed, he added, as 25%-35% of patients with HFrEF remain in NYHA class III despite current drug and device therapies. These patients are moderately symptomatic, meaning they are sick enough that their quality of life is sharply diminished, but not sufficiently ill to qualify for advanced heart therapies, such as cardiac transplantation or a left ventricular assist device.

Dr. Abraham presented the findings of a multinational, prospective, randomized, 6-month, controlled trial involving 140 NYHA class III HFrEF patients in the United States, Canada, Germany, and France. They were randomized to optimal guideline-directed medical therapy alone or in conjunction with baroreflex activation therapy (BAT), a form of neuromodulatory therapy involving electrical stimulation of the carotid baroreflex baroreceptor delivered by an implanted device similar to a pacemaker.

Progressive heart failure is characterized by increased sympathetic and reduced parasympathetic nerve activity. BAT addresses both abnormalities.

“This form of neuromodulation differs from other forms of neuromodulation in that it does not target a peripheral efferent nerve, but rather it targets the carotid baroreceptor. It targets afferent signals to the brain, which then produce an integrated autonomic nervous system response resulting in inhibition of sympathetic activity and enhancement of parasympathetic activity. So this is a physiologic form of autonomic rebalancing that is mediated via the CNS,” explained Dr. Abraham, professor of medicine and director of the division of cardiovascular medicine at Ohio State University, Columbus.

The primary safety endpoint was freedom from system- and procedure-related major adverse neurologic and cardiovascular events at 6 months. The rate was 97.2%. There were no deaths, and complications – all of which occurred within the first 7 days – were few and short lived, with rates similar to those seen with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT). The BAT device, known as the CVRx Barostim neo, did not interact with the ICDs and CRT devices present in a large number of participants. No hypotension occurred in this normotensive HFrEF population.

To place the efficacy outcomes in perspective, Dr. Abraham continued, it’s worth noting that the average 19.5-point between-group difference favoring BAT in scores on the Minnesota Living with Heart Failure Quality of Life Questionnaire (MLHFQ) at 6 months compared to a baseline of 45 points dwarfs the benefits obtainable with standard therapies.

“Please remember that our best drug therapies for HFrEF – ACE inhibitors and beta blockers– improve the MLHFQ score by 4 or 5 points, and cardiac resynchronization therapy improves that score by an average of 9 or 10 points,” he said. From a baseline of 300 meters, the 6-minute hall walk distance improved by 58 meters more in the BAT group than in controls. By comparison, CRT improves the distance walked in 6 minutes by about 30 meters.

“The magnitude of benefit of BAT exceeds that seen with standard therapies, it was seen on top of those standard therapies, and it certainly falls into a range that would be considered clinically meaningful,” the cardiologist asserted.

Left ventricular ejection fraction improved in the BAT group by an average of 2.4% from a baseline of 24% while decreasing by 0.1% in controls. The between-group difference in NT-proBNP at 6 months was 342 pg/mL in favor of the BAT group, starting from a baseline level of roughly 1,300 pg/mL.

The BAT group averaged 6.95 hospital days per year for worsening heart failure during the 6 months prior to enrollment and 0.67 days per year in the 6 months following device activation, for an adjusted 82% relative risk reduction. In contrast, hospital days for heart failure remained steady in controls. The possibility of a new treatment that reduces heart failure hospitalizations is of particular interest in light of the enormous financial burden such hospitalizations currently place upon the Medicare system.

Simultaneously with Dr. Abraham’s presentation at ACC 15, the study manuscript was published online (JACC: Heart Failure 2015 [doi: 10.1016/j.jchf.2015.02.006]).

Dr. Abraham is a consultant to CVRx (which funded the study), as well as Novartis, St. Jude Medical, CardioMEMS, and Abbott Vascular. 

bjancin@frontlinemedcom.com

SAN DIEGO– Baroreflex activation therapy showed promise as an important new device therapy for patients with New York Heart Association Class III heart failure, according to researchers.

In a preliminary randomized trial, the investigational therapy demonstrated safety comparable to that of established device therapies for heart failure. And it significantly improved functional status, exercise capacity, and quality of life while reducing levels of the biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) and days-in-hospital for worsening heart failure, Dr. William T. Abraham said at the annual meeting of the American College of Cardiology.

“The trial showed important results,” he said. “If these observations are confirmed in larger studies, baroreflex activation therapy may offer a new addition for the treatment of advanced heart failure patients with a reduced left ventricular ejection fraction.”

Novel therapies for patients with NYHA class III heart failure with a reduced ejection fraction (HFrEF) are sorely needed, he added, as 25%-35% of patients with HFrEF remain in NYHA class III despite current drug and device therapies. These patients are moderately symptomatic, meaning they are sick enough that their quality of life is sharply diminished, but not sufficiently ill to qualify for advanced heart therapies, such as cardiac transplantation or a left ventricular assist device.

Dr. Abraham presented the findings of a multinational, prospective, randomized, 6-month, controlled trial involving 140 NYHA class III HFrEF patients in the United States, Canada, Germany, and France. They were randomized to optimal guideline-directed medical therapy alone or in conjunction with baroreflex activation therapy (BAT), a form of neuromodulatory therapy involving electrical stimulation of the carotid baroreflex baroreceptor delivered by an implanted device similar to a pacemaker.

Progressive heart failure is characterized by increased sympathetic and reduced parasympathetic nerve activity. BAT addresses both abnormalities.

“This form of neuromodulation differs from other forms of neuromodulation in that it does not target a peripheral efferent nerve, but rather it targets the carotid baroreceptor. It targets afferent signals to the brain, which then produce an integrated autonomic nervous system response resulting in inhibition of sympathetic activity and enhancement of parasympathetic activity. So this is a physiologic form of autonomic rebalancing that is mediated via the CNS,” explained Dr. Abraham, professor of medicine and director of the division of cardiovascular medicine at Ohio State University, Columbus.

The primary safety endpoint was freedom from system- and procedure-related major adverse neurologic and cardiovascular events at 6 months. The rate was 97.2%. There were no deaths, and complications – all of which occurred within the first 7 days – were few and short lived, with rates similar to those seen with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT). The BAT device, known as the CVRx Barostim neo, did not interact with the ICDs and CRT devices present in a large number of participants. No hypotension occurred in this normotensive HFrEF population.

To place the efficacy outcomes in perspective, Dr. Abraham continued, it’s worth noting that the average 19.5-point between-group difference favoring BAT in scores on the Minnesota Living with Heart Failure Quality of Life Questionnaire (MLHFQ) at 6 months compared to a baseline of 45 points dwarfs the benefits obtainable with standard therapies.

“Please remember that our best drug therapies for HFrEF – ACE inhibitors and beta blockers– improve the MLHFQ score by 4 or 5 points, and cardiac resynchronization therapy improves that score by an average of 9 or 10 points,” he said. From a baseline of 300 meters, the 6-minute hall walk distance improved by 58 meters more in the BAT group than in controls. By comparison, CRT improves the distance walked in 6 minutes by about 30 meters.

“The magnitude of benefit of BAT exceeds that seen with standard therapies, it was seen on top of those standard therapies, and it certainly falls into a range that would be considered clinically meaningful,” the cardiologist asserted.

Left ventricular ejection fraction improved in the BAT group by an average of 2.4% from a baseline of 24% while decreasing by 0.1% in controls. The between-group difference in NT-proBNP at 6 months was 342 pg/mL in favor of the BAT group, starting from a baseline level of roughly 1,300 pg/mL.

The BAT group averaged 6.95 hospital days per year for worsening heart failure during the 6 months prior to enrollment and 0.67 days per year in the 6 months following device activation, for an adjusted 82% relative risk reduction. In contrast, hospital days for heart failure remained steady in controls. The possibility of a new treatment that reduces heart failure hospitalizations is of particular interest in light of the enormous financial burden such hospitalizations currently place upon the Medicare system.

Simultaneously with Dr. Abraham’s presentation at ACC 15, the study manuscript was published online (JACC: Heart Failure 2015 [doi: 10.1016/j.jchf.2015.02.006]).

Dr. Abraham is a consultant to CVRx (which funded the study), as well as Novartis, St. Jude Medical, CardioMEMS, and Abbott Vascular. 

bjancin@frontlinemedcom.com