Heart Failure Society of America (HFSA): Annual Scientific Meeting

SEATTLE – A tiny pump that provides partial support to patients with heart failure may improve outcomes, at least in the short term, for those in the earlier stages of the disease, clinical experience with the device has shown.

The 20 patients in Belgium and Germany who underwent implantation of the newest version of the investigational device had significantly improved hemodynamics, exercise tolerance, and end organ function at a median of 12 weeks’ follow-up, Dr. Daniel Burkhoff reported at the annual meeting of the Heart Failure Society of America.

The rate of adverse events was about 10 per patient-year in the first month after implantation and roughly 3 per patient-year thereafter.

The findings suggest that "significant and sustained improvements in hemodynamics, exercise capacity, and quality of life can be achieved in this population," commented Dr. Burkhoff of Columbia University in New York and also medical director of CircuLite.

The micropump (known as the Synergy System and manufactured by CircuLite in Saddle Brook, N.J.) received the CE mark for use in Europe in September.

Discussant Dr. Robert L. Kormos of the University of Pittsburgh Medical Center maintained that longer-term data will be needed to assess true sustainability of the results. He also questioned whether the 20 patients described were similar clinically to the entire group of 58 patients who have received some version of the device.

It’s unclear at this point if a U.S. trial designed for Food and Drug Administration approval will focus on a combined heart failure indication versus that of a separate indication as a bridge to transplant or destination therapy, he said.

"The trial suggested that a major reduction in adverse events compared to those seen with contemporary LVADs [left ventricular assist devices] can be achieved through the strategy of early implantation in the spectrum of heart failure and the minimally invasive approach that was used," Dr. Kormos commented. However, the relative contributions of patient selection and the device to this favorable outcome were unclear, he added.

"I do consider this in many respects a landmark [study]. This opens a window to a new therapy that many of us, especially as surgeons, are looking forward to, specifically because it allows us to operate on a group of patients who have fewer comorbidities than we currently see," he concluded.

The patients in the study had heart failure with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 4 or higher disease, corresponding to New York Heart Association class III or IV, and were symptomatic despite appropriate medical therapy and cardiac resynchronization therapy. They were ambulatory, were not dependent on inotropes, and had recently had a hospitalization and/or increasing medical visits.

The device was used for any of three management strategies, Dr. Burkhoff noted: bridge to transplant, destination therapy, or bridge to decision. "We have not made a distinction between these because especially in Europe, the wait times for heart transplant are so long that these traditional boundaries are really being blurred," he explained.

The patients underwent implantation of the micropump, which is the size of a AA battery, weighs 25 g, and pumps 1.5-4.25 L/min. It is implanted subcutaneously and extrathoracically in a pacemaker pocket with an off-pump minithoracotomy procedure. The device pumps blood from the left atrium to the subclavian artery to increase circulation.

Of the 20 patients who received the most current version of the device, 82% had an implantable cardioverter-defibrillator and 65% had had cardiac resynchronization therapy.

"In terms of the postoperative care, it’s important to consider the differences between this and other VADs [ventricular assist devices]," Dr. Burkhoff maintained, noting the typically short times with the micropump to extubation (within hours), chest tube removal (1 day), and ambulation (1-2 days).

"In terms of the hemodynamic effectiveness, these data show that use of this partial support device can really interrupt and reverse the hemodynamic derangements of heart failure," he said.

Specifically, at a median follow-up of 12 weeks, patients had significant improvements from baseline in cardiac output (by about 1 L/min), pulmonary capillary wedge pressure (10 mm Hg), central venous pressure (5 mm Hg), pulmonary artery pressures (5-15 mm Hg), and pulmonary vascular resistance (1 Wood unit).

Because the device provides only partial cardiac support, the heart still beats regularly; thus, arterial systolic and diastolic pressures did not change significantly, and normal pulsatility in the arterial system was preserved.

Patients also had significant improvements in exercise tolerance as assessed with the 6-minute walk test (by 120 m) and peak VO₂ (1.6 mL/kg per minute), and in end organ function, as assessed from creatinine level (0.5 mg/dL), but not in total bilirubin level (0.2 m/dL.

The rate of adverse events, predominantly bleeding, was 9.9 per patient-year in the first month after implantation and 2.5 per patient-year thereafter.

There were three deaths due to perioperative complications; two were related to bleeding, and one was related to a stroke after administration of two doses of vitamin K.

Taken together, the adverse events and deaths "remind us that this is still a surgical procedure, and patients are exposed to certain risks," he said.

Dr. Burkhoff disclosed that he is medical director of and a stockholder in CircuLite. Dr. Kormos disclosed that he receives research support from HeartWare. The study was sponsored by CircuLite.

SEATTLE – A tiny pump that provides partial support to patients with heart failure may improve outcomes, at least in the short term, for those in the earlier stages of the disease, clinical experience with the device has shown.

The 20 patients in Belgium and Germany who underwent implantation of the newest version of the investigational device had significantly improved hemodynamics, exercise tolerance, and end organ function at a median of 12 weeks’ follow-up, Dr. Daniel Burkhoff reported at the annual meeting of the Heart Failure Society of America.

The rate of adverse events was about 10 per patient-year in the first month after implantation and roughly 3 per patient-year thereafter.

The findings suggest that "significant and sustained improvements in hemodynamics, exercise capacity, and quality of life can be achieved in this population," commented Dr. Burkhoff of Columbia University in New York and also medical director of CircuLite.

The micropump (known as the Synergy System and manufactured by CircuLite in Saddle Brook, N.J.) received the CE mark for use in Europe in September.

Discussant Dr. Robert L. Kormos of the University of Pittsburgh Medical Center maintained that longer-term data will be needed to assess true sustainability of the results. He also questioned whether the 20 patients described were similar clinically to the entire group of 58 patients who have received some version of the device.

It’s unclear at this point if a U.S. trial designed for Food and Drug Administration approval will focus on a combined heart failure indication versus that of a separate indication as a bridge to transplant or destination therapy, he said.

"The trial suggested that a major reduction in adverse events compared to those seen with contemporary LVADs [left ventricular assist devices] can be achieved through the strategy of early implantation in the spectrum of heart failure and the minimally invasive approach that was used," Dr. Kormos commented. However, the relative contributions of patient selection and the device to this favorable outcome were unclear, he added.

"I do consider this in many respects a landmark [study]. This opens a window to a new therapy that many of us, especially as surgeons, are looking forward to, specifically because it allows us to operate on a group of patients who have fewer comorbidities than we currently see," he concluded.

The patients in the study had heart failure with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 4 or higher disease, corresponding to New York Heart Association class III or IV, and were symptomatic despite appropriate medical therapy and cardiac resynchronization therapy. They were ambulatory, were not dependent on inotropes, and had recently had a hospitalization and/or increasing medical visits.

The device was used for any of three management strategies, Dr. Burkhoff noted: bridge to transplant, destination therapy, or bridge to decision. "We have not made a distinction between these because especially in Europe, the wait times for heart transplant are so long that these traditional boundaries are really being blurred," he explained.

The patients underwent implantation of the micropump, which is the size of a AA battery, weighs 25 g, and pumps 1.5-4.25 L/min. It is implanted subcutaneously and extrathoracically in a pacemaker pocket with an off-pump minithoracotomy procedure. The device pumps blood from the left atrium to the subclavian artery to increase circulation.

Of the 20 patients who received the most current version of the device, 82% had an implantable cardioverter-defibrillator and 65% had had cardiac resynchronization therapy.

"In terms of the postoperative care, it’s important to consider the differences between this and other VADs [ventricular assist devices]," Dr. Burkhoff maintained, noting the typically short times with the micropump to extubation (within hours), chest tube removal (1 day), and ambulation (1-2 days).

"In terms of the hemodynamic effectiveness, these data show that use of this partial support device can really interrupt and reverse the hemodynamic derangements of heart failure," he said.

Specifically, at a median follow-up of 12 weeks, patients had significant improvements from baseline in cardiac output (by about 1 L/min), pulmonary capillary wedge pressure (10 mm Hg), central venous pressure (5 mm Hg), pulmonary artery pressures (5-15 mm Hg), and pulmonary vascular resistance (1 Wood unit).

Because the device provides only partial cardiac support, the heart still beats regularly; thus, arterial systolic and diastolic pressures did not change significantly, and normal pulsatility in the arterial system was preserved.

Patients also had significant improvements in exercise tolerance as assessed with the 6-minute walk test (by 120 m) and peak VO₂ (1.6 mL/kg per minute), and in end organ function, as assessed from creatinine level (0.5 mg/dL), but not in total bilirubin level (0.2 m/dL.

The rate of adverse events, predominantly bleeding, was 9.9 per patient-year in the first month after implantation and 2.5 per patient-year thereafter.

There were three deaths due to perioperative complications; two were related to bleeding, and one was related to a stroke after administration of two doses of vitamin K.

Taken together, the adverse events and deaths "remind us that this is still a surgical procedure, and patients are exposed to certain risks," he said.

Dr. Burkhoff disclosed that he is medical director of and a stockholder in CircuLite. Dr. Kormos disclosed that he receives research support from HeartWare. The study was sponsored by CircuLite.

SEATTLE – A tiny pump that provides partial support to patients with heart failure may improve outcomes, at least in the short term, for those in the earlier stages of the disease, clinical experience with the device has shown.

The 20 patients in Belgium and Germany who underwent implantation of the newest version of the investigational device had significantly improved hemodynamics, exercise tolerance, and end organ function at a median of 12 weeks’ follow-up, Dr. Daniel Burkhoff reported at the annual meeting of the Heart Failure Society of America.

The rate of adverse events was about 10 per patient-year in the first month after implantation and roughly 3 per patient-year thereafter.

The findings suggest that "significant and sustained improvements in hemodynamics, exercise capacity, and quality of life can be achieved in this population," commented Dr. Burkhoff of Columbia University in New York and also medical director of CircuLite.

The micropump (known as the Synergy System and manufactured by CircuLite in Saddle Brook, N.J.) received the CE mark for use in Europe in September.

Discussant Dr. Robert L. Kormos of the University of Pittsburgh Medical Center maintained that longer-term data will be needed to assess true sustainability of the results. He also questioned whether the 20 patients described were similar clinically to the entire group of 58 patients who have received some version of the device.

It’s unclear at this point if a U.S. trial designed for Food and Drug Administration approval will focus on a combined heart failure indication versus that of a separate indication as a bridge to transplant or destination therapy, he said.

"The trial suggested that a major reduction in adverse events compared to those seen with contemporary LVADs [left ventricular assist devices] can be achieved through the strategy of early implantation in the spectrum of heart failure and the minimally invasive approach that was used," Dr. Kormos commented. However, the relative contributions of patient selection and the device to this favorable outcome were unclear, he added.

"I do consider this in many respects a landmark [study]. This opens a window to a new therapy that many of us, especially as surgeons, are looking forward to, specifically because it allows us to operate on a group of patients who have fewer comorbidities than we currently see," he concluded.

The patients in the study had heart failure with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 4 or higher disease, corresponding to New York Heart Association class III or IV, and were symptomatic despite appropriate medical therapy and cardiac resynchronization therapy. They were ambulatory, were not dependent on inotropes, and had recently had a hospitalization and/or increasing medical visits.

The device was used for any of three management strategies, Dr. Burkhoff noted: bridge to transplant, destination therapy, or bridge to decision. "We have not made a distinction between these because especially in Europe, the wait times for heart transplant are so long that these traditional boundaries are really being blurred," he explained.

The patients underwent implantation of the micropump, which is the size of a AA battery, weighs 25 g, and pumps 1.5-4.25 L/min. It is implanted subcutaneously and extrathoracically in a pacemaker pocket with an off-pump minithoracotomy procedure. The device pumps blood from the left atrium to the subclavian artery to increase circulation.

Of the 20 patients who received the most current version of the device, 82% had an implantable cardioverter-defibrillator and 65% had had cardiac resynchronization therapy.

"In terms of the postoperative care, it’s important to consider the differences between this and other VADs [ventricular assist devices]," Dr. Burkhoff maintained, noting the typically short times with the micropump to extubation (within hours), chest tube removal (1 day), and ambulation (1-2 days).

"In terms of the hemodynamic effectiveness, these data show that use of this partial support device can really interrupt and reverse the hemodynamic derangements of heart failure," he said.

Specifically, at a median follow-up of 12 weeks, patients had significant improvements from baseline in cardiac output (by about 1 L/min), pulmonary capillary wedge pressure (10 mm Hg), central venous pressure (5 mm Hg), pulmonary artery pressures (5-15 mm Hg), and pulmonary vascular resistance (1 Wood unit).

Because the device provides only partial cardiac support, the heart still beats regularly; thus, arterial systolic and diastolic pressures did not change significantly, and normal pulsatility in the arterial system was preserved.

Patients also had significant improvements in exercise tolerance as assessed with the 6-minute walk test (by 120 m) and peak VO₂ (1.6 mL/kg per minute), and in end organ function, as assessed from creatinine level (0.5 mg/dL), but not in total bilirubin level (0.2 m/dL.

The rate of adverse events, predominantly bleeding, was 9.9 per patient-year in the first month after implantation and 2.5 per patient-year thereafter.

There were three deaths due to perioperative complications; two were related to bleeding, and one was related to a stroke after administration of two doses of vitamin K.

Taken together, the adverse events and deaths "remind us that this is still a surgical procedure, and patients are exposed to certain risks," he said.

Dr. Burkhoff disclosed that he is medical director of and a stockholder in CircuLite. Dr. Kormos disclosed that he receives research support from HeartWare. The study was sponsored by CircuLite.

SEATTLE – Smartphones may soon be harnessed for monitoring patients with heart failure, offering advantages such as remote assessment and early prediction of decompensation.

A recent survey suggested that 88% of physicians would like to be able to monitor measures of their patients’ health status at home, including many relevant to heart failure. "Those metrics will become more and more available" with smartphone technology, noted Dr. David E. Albert, founder and chief scientific officer of AliveCor Inc., a manufacturer of mobile monitors, including the investigational AliveCor Smartphone System.

Image Courtesy AliveCor

The device is an ECG monitor that is in clinical trials and under review by the Food and Drug Administration. A patient uses a smartphone and an app to record a clinical-quality ECG that is securely stored and processed in cloud computing-based server, and can be accessed by a physician anywhere in the world.

The device can evaluate at least three cardiac indices used in the monitoring of heart failure, according to Dr. Albert: cardiac rhythm, heart rate, and heart rate variability.

When it comes to cardiac rhythm, smartphones can be used to detect arrhythmias such as atrial fibrillation (J. Am. Coll. Cardiol. 2012;59:E726). He recounted the story of a man in Mumbai, India, experiencing asymptomatic ischemia-induced rhythm changes that were recorded with a smartphone. Physicians in Oklahoma City and Los Angeles identified the arrhythmia and notified the patient, who then went to his physician.

The ECG obtained with the smartphone has the same quality as a 12-lead ECG obtained with state-of-the-art equipment in the clinic, he said. Also, data suggest that a daily ECG is second only to implanted devices for detecting atrial fibrillation (Pacing Clin. Electrophysiol. 2007;30:458-62). "So it’s better than a 24-hour Holter, even now, and our very intermittent 7-day Holters."

Heart rate, the second index, may be a key therapeutic target in heart failure. Here, too, the smartphone-assessed heart rate is just as accurate as clinically measured heart rate, with sensitivity exceeding 99% for QRS detection (and thus R to R intervals), putting it on par with the 12-lead ECG, according to Dr. Albert.

Heart rate variability, the third index, potentially could be used as an index to guide the need for intervention before progression to decompensated heart failure.

Decompensation develops through a series of changes beginning with increasing preload and autonomic adaptation, and culminating in weight gain, symptoms, and hospitalization (Curr. Heart Fail. Rep. 2009;6:287-92). "Obviously, we want to operate on the left side of this graph, where filling and autonomic adaptation are the places we can intervene early," he noted.

Short-term heart rate variability obtained during 8 minutes of paced breathing has been shown to predict sudden cardiac death in patients having chronic heart failure (Circulation 2003;107:565-70), and smartphones can readily be used for such measurement.

The timing of events during the cardiac cycle may also be informative, according to Dr. Albert. These events can be assessed with seismocardiography, whereby vibrations in the chest are measured with an accelerometer placed on the sternum (Chest 1991;100:991-3) and can be combined with ECG data to derive the Tei index, a global measure of cardiac performance (J. Cardiol. 1995;26:135-6). Although the necessary data can be collected with a somewhat elaborate laboratory setup (J. Med. Biol. Engineer 2012;32:103-10), they can also be obtained easily with a smartphone placed on the chest.

"We can measure isovolumic contraction time, isovolumic relaxation time, and ejection time, and develop in 30 seconds not only rate, rhythm, variability, but now a modified Tei index, an index of performance, and as many papers have said, an index of preload status," he noted.

"With today’s smartphones, which will only get more powerful, we can evaluate cardiac rhythm, or our patients can. They can evaluate their cardiac rate, their heart rate variability, and probably potentially – unproven yet very interesting – their ventricular performance and their preload status, enabling that [information] to be injected into the network, enabling certainly intervention and maybe self-care," Dr. Albert concluded.

A session attendee said that this new technology "sounds very good. But we know even when [clinical devices] are used just to study time intervals, there were a lot of artifacts, and accuracy was not very easily determined. Certainly, with this kind of platform, there must be problems with accuracy and artifact in recordings."

It is still early in development of this technology, Dr. Albert acknowledged. "But understand that we have processing power that’s quite unbelievable. ... What I can tell you is that we can measure these variables; what I can’t tell you is how valuable they are going to be."

Another attendee expressed concern over the vast amount of data that would be generated and then require analysis. "How far are we going to go before we get to the point where we need a different layer besides the physician, the nurses, the PAs? If you are going to swamp us with this much data, there is no way a busy doctor seeing 20 heart patients a day, going to the cath lab, can possibly figure out so much data, what’s important, what’s not," he said.

Recently, the venture capitalist Vinod Khosla put forth a paper calling for fewer doctors and more algorithms, Dr. Albert replied. "I don’t think we will disenfranchise physicians, but I do believe the power of big data will become more and more important for all of us in the management of all our patients," he predicted.

"Apps will be in our pockets as professionals; they will be in our patients’ pockets. And we must figure out how to utilize them to help us deal with major health care issues of the day."

Dr. Albert disclosed that he is member of the board of directors of, a full-time salaried employee of, and an equity shareholder in AliveCor.

SEATTLE – Smartphones may soon be harnessed for monitoring patients with heart failure, offering advantages such as remote assessment and early prediction of decompensation.

A recent survey suggested that 88% of physicians would like to be able to monitor measures of their patients’ health status at home, including many relevant to heart failure. "Those metrics will become more and more available" with smartphone technology, noted Dr. David E. Albert, founder and chief scientific officer of AliveCor Inc., a manufacturer of mobile monitors, including the investigational AliveCor Smartphone System.

Image Courtesy AliveCor

The device is an ECG monitor that is in clinical trials and under review by the Food and Drug Administration. A patient uses a smartphone and an app to record a clinical-quality ECG that is securely stored and processed in cloud computing-based server, and can be accessed by a physician anywhere in the world.

The device can evaluate at least three cardiac indices used in the monitoring of heart failure, according to Dr. Albert: cardiac rhythm, heart rate, and heart rate variability.

When it comes to cardiac rhythm, smartphones can be used to detect arrhythmias such as atrial fibrillation (J. Am. Coll. Cardiol. 2012;59:E726). He recounted the story of a man in Mumbai, India, experiencing asymptomatic ischemia-induced rhythm changes that were recorded with a smartphone. Physicians in Oklahoma City and Los Angeles identified the arrhythmia and notified the patient, who then went to his physician.

The ECG obtained with the smartphone has the same quality as a 12-lead ECG obtained with state-of-the-art equipment in the clinic, he said. Also, data suggest that a daily ECG is second only to implanted devices for detecting atrial fibrillation (Pacing Clin. Electrophysiol. 2007;30:458-62). "So it’s better than a 24-hour Holter, even now, and our very intermittent 7-day Holters."

Heart rate, the second index, may be a key therapeutic target in heart failure. Here, too, the smartphone-assessed heart rate is just as accurate as clinically measured heart rate, with sensitivity exceeding 99% for QRS detection (and thus R to R intervals), putting it on par with the 12-lead ECG, according to Dr. Albert.

Heart rate variability, the third index, potentially could be used as an index to guide the need for intervention before progression to decompensated heart failure.

Decompensation develops through a series of changes beginning with increasing preload and autonomic adaptation, and culminating in weight gain, symptoms, and hospitalization (Curr. Heart Fail. Rep. 2009;6:287-92). "Obviously, we want to operate on the left side of this graph, where filling and autonomic adaptation are the places we can intervene early," he noted.

Short-term heart rate variability obtained during 8 minutes of paced breathing has been shown to predict sudden cardiac death in patients having chronic heart failure (Circulation 2003;107:565-70), and smartphones can readily be used for such measurement.

The timing of events during the cardiac cycle may also be informative, according to Dr. Albert. These events can be assessed with seismocardiography, whereby vibrations in the chest are measured with an accelerometer placed on the sternum (Chest 1991;100:991-3) and can be combined with ECG data to derive the Tei index, a global measure of cardiac performance (J. Cardiol. 1995;26:135-6). Although the necessary data can be collected with a somewhat elaborate laboratory setup (J. Med. Biol. Engineer 2012;32:103-10), they can also be obtained easily with a smartphone placed on the chest.

"We can measure isovolumic contraction time, isovolumic relaxation time, and ejection time, and develop in 30 seconds not only rate, rhythm, variability, but now a modified Tei index, an index of performance, and as many papers have said, an index of preload status," he noted.

"With today’s smartphones, which will only get more powerful, we can evaluate cardiac rhythm, or our patients can. They can evaluate their cardiac rate, their heart rate variability, and probably potentially – unproven yet very interesting – their ventricular performance and their preload status, enabling that [information] to be injected into the network, enabling certainly intervention and maybe self-care," Dr. Albert concluded.

A session attendee said that this new technology "sounds very good. But we know even when [clinical devices] are used just to study time intervals, there were a lot of artifacts, and accuracy was not very easily determined. Certainly, with this kind of platform, there must be problems with accuracy and artifact in recordings."

It is still early in development of this technology, Dr. Albert acknowledged. "But understand that we have processing power that’s quite unbelievable. ... What I can tell you is that we can measure these variables; what I can’t tell you is how valuable they are going to be."

Another attendee expressed concern over the vast amount of data that would be generated and then require analysis. "How far are we going to go before we get to the point where we need a different layer besides the physician, the nurses, the PAs? If you are going to swamp us with this much data, there is no way a busy doctor seeing 20 heart patients a day, going to the cath lab, can possibly figure out so much data, what’s important, what’s not," he said.

Recently, the venture capitalist Vinod Khosla put forth a paper calling for fewer doctors and more algorithms, Dr. Albert replied. "I don’t think we will disenfranchise physicians, but I do believe the power of big data will become more and more important for all of us in the management of all our patients," he predicted.

"Apps will be in our pockets as professionals; they will be in our patients’ pockets. And we must figure out how to utilize them to help us deal with major health care issues of the day."

Dr. Albert disclosed that he is member of the board of directors of, a full-time salaried employee of, and an equity shareholder in AliveCor.

SEATTLE – Smartphones may soon be harnessed for monitoring patients with heart failure, offering advantages such as remote assessment and early prediction of decompensation.

A recent survey suggested that 88% of physicians would like to be able to monitor measures of their patients’ health status at home, including many relevant to heart failure. "Those metrics will become more and more available" with smartphone technology, noted Dr. David E. Albert, founder and chief scientific officer of AliveCor Inc., a manufacturer of mobile monitors, including the investigational AliveCor Smartphone System.

Image Courtesy AliveCor

The device is an ECG monitor that is in clinical trials and under review by the Food and Drug Administration. A patient uses a smartphone and an app to record a clinical-quality ECG that is securely stored and processed in cloud computing-based server, and can be accessed by a physician anywhere in the world.

The device can evaluate at least three cardiac indices used in the monitoring of heart failure, according to Dr. Albert: cardiac rhythm, heart rate, and heart rate variability.

When it comes to cardiac rhythm, smartphones can be used to detect arrhythmias such as atrial fibrillation (J. Am. Coll. Cardiol. 2012;59:E726). He recounted the story of a man in Mumbai, India, experiencing asymptomatic ischemia-induced rhythm changes that were recorded with a smartphone. Physicians in Oklahoma City and Los Angeles identified the arrhythmia and notified the patient, who then went to his physician.

The ECG obtained with the smartphone has the same quality as a 12-lead ECG obtained with state-of-the-art equipment in the clinic, he said. Also, data suggest that a daily ECG is second only to implanted devices for detecting atrial fibrillation (Pacing Clin. Electrophysiol. 2007;30:458-62). "So it’s better than a 24-hour Holter, even now, and our very intermittent 7-day Holters."

Heart rate, the second index, may be a key therapeutic target in heart failure. Here, too, the smartphone-assessed heart rate is just as accurate as clinically measured heart rate, with sensitivity exceeding 99% for QRS detection (and thus R to R intervals), putting it on par with the 12-lead ECG, according to Dr. Albert.

Heart rate variability, the third index, potentially could be used as an index to guide the need for intervention before progression to decompensated heart failure.

Decompensation develops through a series of changes beginning with increasing preload and autonomic adaptation, and culminating in weight gain, symptoms, and hospitalization (Curr. Heart Fail. Rep. 2009;6:287-92). "Obviously, we want to operate on the left side of this graph, where filling and autonomic adaptation are the places we can intervene early," he noted.

Short-term heart rate variability obtained during 8 minutes of paced breathing has been shown to predict sudden cardiac death in patients having chronic heart failure (Circulation 2003;107:565-70), and smartphones can readily be used for such measurement.

The timing of events during the cardiac cycle may also be informative, according to Dr. Albert. These events can be assessed with seismocardiography, whereby vibrations in the chest are measured with an accelerometer placed on the sternum (Chest 1991;100:991-3) and can be combined with ECG data to derive the Tei index, a global measure of cardiac performance (J. Cardiol. 1995;26:135-6). Although the necessary data can be collected with a somewhat elaborate laboratory setup (J. Med. Biol. Engineer 2012;32:103-10), they can also be obtained easily with a smartphone placed on the chest.

"We can measure isovolumic contraction time, isovolumic relaxation time, and ejection time, and develop in 30 seconds not only rate, rhythm, variability, but now a modified Tei index, an index of performance, and as many papers have said, an index of preload status," he noted.

"With today’s smartphones, which will only get more powerful, we can evaluate cardiac rhythm, or our patients can. They can evaluate their cardiac rate, their heart rate variability, and probably potentially – unproven yet very interesting – their ventricular performance and their preload status, enabling that [information] to be injected into the network, enabling certainly intervention and maybe self-care," Dr. Albert concluded.

A session attendee said that this new technology "sounds very good. But we know even when [clinical devices] are used just to study time intervals, there were a lot of artifacts, and accuracy was not very easily determined. Certainly, with this kind of platform, there must be problems with accuracy and artifact in recordings."

It is still early in development of this technology, Dr. Albert acknowledged. "But understand that we have processing power that’s quite unbelievable. ... What I can tell you is that we can measure these variables; what I can’t tell you is how valuable they are going to be."

Another attendee expressed concern over the vast amount of data that would be generated and then require analysis. "How far are we going to go before we get to the point where we need a different layer besides the physician, the nurses, the PAs? If you are going to swamp us with this much data, there is no way a busy doctor seeing 20 heart patients a day, going to the cath lab, can possibly figure out so much data, what’s important, what’s not," he said.

Recently, the venture capitalist Vinod Khosla put forth a paper calling for fewer doctors and more algorithms, Dr. Albert replied. "I don’t think we will disenfranchise physicians, but I do believe the power of big data will become more and more important for all of us in the management of all our patients," he predicted.

"Apps will be in our pockets as professionals; they will be in our patients’ pockets. And we must figure out how to utilize them to help us deal with major health care issues of the day."

Dr. Albert disclosed that he is member of the board of directors of, a full-time salaried employee of, and an equity shareholder in AliveCor.

SEATTLE – Aldosterone antagonists can be used safely and effectively to treat heart failure in real-world practice, and their underuse likely accounts for a sizable share of deaths in this patient population, according to Dr. Gregg C. Fonarow, cochief of the division of cardiology at the University of California, Los Angeles.

These agents are among six heart failure therapies having a class I (highest) recommendation in national guidelines for managing heart failure, he said at the annual meeting of the Heart Failure Society of America. Yet, nearly 68,000 patients with heart failure and reduced left ventricular ejection fraction (LVEF) die each year in the United States because they do not receive these therapies (Am. Heart J. 2011;161:1024-30).

"If we bridged that gap, and assuming the efficacy and effectiveness match, you can see the potential number of lives saved each year. ... And, in fact, the greatest number of lives saved [roughly 21,400] could result from the improved use of aldosterone antagonists, if there were optimal implementation," he said.

Indeed, analyses show that only about one-third of eligible heart failure outpatients (Circ. Heart Fail. 2008;1:98-106) and inpatients (JAMA 2009;302:1658-65) in real-world U.S. practice receive drugs in this class.

Some resistance to the use of aldosterone antagonists – such as spironolactone (brand name Aldactone) and eplerenone (Inspra) – has stemmed from uncertainty as to whether the risk-benefit profile in clinical trials translates to real-world practice, according to Dr. Fonarow.

A recent analysis suggests that among patients with heart failure and reduced LVEF, aldosterone antagonist therapy decreases the risk of death by about 30% and the risk of hospitalization by 35% (Am. Heart J. 2011;161:1024-30). The number needed to treat to prevent a single death in a 36-month period is just eight, and the benefit is incremental to that of other standard therapies.

"There was just a moderate increase in the risk of hyperkalemia and increased creatinine, but overall, safe and well tolerated," he said. "They were shown to be highly cost effective even with fully branded medications at full cost, and the benefits greatly outweighed the potential risks."

However, an analysis of Canadian administrative data showed that after publication of the Randomized Aldactone Evaluation Study (RALES), which found significant benefit of spironolactone in heart failure, there was an increase in prescriptions for the drug but also a concomitant increase in hyperkalemia-related hospitalizations and deaths (N. Engl. J. Med. 2004;351:543-51).

The analysis did not assess benefits and had some limitations, according to Dr. Fonarow. "But after that publication and a few others, a number of notable heart failure experts stated pretty strong viewpoints that aldosterone antagonists are really not safe in real-world clinical practice, the risks outweigh any potential benefits, and they should be reserved only for the most severe heart failure patients and only after all other therapies have been tried and failed."

Yet, other studies have suggested, for example, that every 10% increase in aldosterone antagonist use among hospitalized patients is associated with a 6% reduction in all-cause mortality over the following year (Am. Heart J. 2010;159:406-13). Furthermore, in the context of careful monitoring, with increasing use of spironolactone, hyperkalemia is not problematic (BMJ 2010;340:c1768).

"Certainly, some of the data have had a number of individuals saying, ‘We need to get away from evidence guidelines and performance measures, and individualize therapy,’ and ‘I should pick and choose therapy as I think,’ and ‘Findings from clinical trials are not applicable to my patients, they are much more complex, and I know my patients are going to do well because I give them highly personalized care rather than cookbook medicine,’" Dr. Fonarow commented. "That is certainly not a very scientific or satisfying type of approach."

Experience from IMPROVE HF suggests that a performance improvement program can safely and effectively increase the use of aldosterone antagonists for heart failure in a real-world setting (Circulation 2010;122:585-96). The program led to a near doubling of use of these agents over 2 years. "At the same time, did we see any increase in inappropriate or ineligible patients being treated? No, the rates for patients with absolute contraindications or relative contraindications was very small, below 1%, and did not increase," he said.

"Treatment gaps between guidelines and practice exist for heart failure and, as a result, large numbers of patients are having hospitalizations and fatal events that could have been prevented. This is particularly true for aldosterone antagonists," Dr. Fonarow concluded. "Bridging the gap between evidence and clinical practice systems is needed, and by applying these evidence-based therapies with the appropriate monitoring and the appropriate selection of patients, we can do this in a way that truly will improve outcomes."

Dr. Fonarow disclosed that he is a consultant to and/or receives honoraria or research funding from Novartis and Medtronic.

SEATTLE – Aldosterone antagonists can be used safely and effectively to treat heart failure in real-world practice, and their underuse likely accounts for a sizable share of deaths in this patient population, according to Dr. Gregg C. Fonarow, cochief of the division of cardiology at the University of California, Los Angeles.

These agents are among six heart failure therapies having a class I (highest) recommendation in national guidelines for managing heart failure, he said at the annual meeting of the Heart Failure Society of America. Yet, nearly 68,000 patients with heart failure and reduced left ventricular ejection fraction (LVEF) die each year in the United States because they do not receive these therapies (Am. Heart J. 2011;161:1024-30).

"If we bridged that gap, and assuming the efficacy and effectiveness match, you can see the potential number of lives saved each year. ... And, in fact, the greatest number of lives saved [roughly 21,400] could result from the improved use of aldosterone antagonists, if there were optimal implementation," he said.

Indeed, analyses show that only about one-third of eligible heart failure outpatients (Circ. Heart Fail. 2008;1:98-106) and inpatients (JAMA 2009;302:1658-65) in real-world U.S. practice receive drugs in this class.

Some resistance to the use of aldosterone antagonists – such as spironolactone (brand name Aldactone) and eplerenone (Inspra) – has stemmed from uncertainty as to whether the risk-benefit profile in clinical trials translates to real-world practice, according to Dr. Fonarow.

A recent analysis suggests that among patients with heart failure and reduced LVEF, aldosterone antagonist therapy decreases the risk of death by about 30% and the risk of hospitalization by 35% (Am. Heart J. 2011;161:1024-30). The number needed to treat to prevent a single death in a 36-month period is just eight, and the benefit is incremental to that of other standard therapies.

"There was just a moderate increase in the risk of hyperkalemia and increased creatinine, but overall, safe and well tolerated," he said. "They were shown to be highly cost effective even with fully branded medications at full cost, and the benefits greatly outweighed the potential risks."

However, an analysis of Canadian administrative data showed that after publication of the Randomized Aldactone Evaluation Study (RALES), which found significant benefit of spironolactone in heart failure, there was an increase in prescriptions for the drug but also a concomitant increase in hyperkalemia-related hospitalizations and deaths (N. Engl. J. Med. 2004;351:543-51).

The analysis did not assess benefits and had some limitations, according to Dr. Fonarow. "But after that publication and a few others, a number of notable heart failure experts stated pretty strong viewpoints that aldosterone antagonists are really not safe in real-world clinical practice, the risks outweigh any potential benefits, and they should be reserved only for the most severe heart failure patients and only after all other therapies have been tried and failed."

Yet, other studies have suggested, for example, that every 10% increase in aldosterone antagonist use among hospitalized patients is associated with a 6% reduction in all-cause mortality over the following year (Am. Heart J. 2010;159:406-13). Furthermore, in the context of careful monitoring, with increasing use of spironolactone, hyperkalemia is not problematic (BMJ 2010;340:c1768).

"Certainly, some of the data have had a number of individuals saying, ‘We need to get away from evidence guidelines and performance measures, and individualize therapy,’ and ‘I should pick and choose therapy as I think,’ and ‘Findings from clinical trials are not applicable to my patients, they are much more complex, and I know my patients are going to do well because I give them highly personalized care rather than cookbook medicine,’" Dr. Fonarow commented. "That is certainly not a very scientific or satisfying type of approach."

Experience from IMPROVE HF suggests that a performance improvement program can safely and effectively increase the use of aldosterone antagonists for heart failure in a real-world setting (Circulation 2010;122:585-96). The program led to a near doubling of use of these agents over 2 years. "At the same time, did we see any increase in inappropriate or ineligible patients being treated? No, the rates for patients with absolute contraindications or relative contraindications was very small, below 1%, and did not increase," he said.

"Treatment gaps between guidelines and practice exist for heart failure and, as a result, large numbers of patients are having hospitalizations and fatal events that could have been prevented. This is particularly true for aldosterone antagonists," Dr. Fonarow concluded. "Bridging the gap between evidence and clinical practice systems is needed, and by applying these evidence-based therapies with the appropriate monitoring and the appropriate selection of patients, we can do this in a way that truly will improve outcomes."

Dr. Fonarow disclosed that he is a consultant to and/or receives honoraria or research funding from Novartis and Medtronic.

SEATTLE – Aldosterone antagonists can be used safely and effectively to treat heart failure in real-world practice, and their underuse likely accounts for a sizable share of deaths in this patient population, according to Dr. Gregg C. Fonarow, cochief of the division of cardiology at the University of California, Los Angeles.

These agents are among six heart failure therapies having a class I (highest) recommendation in national guidelines for managing heart failure, he said at the annual meeting of the Heart Failure Society of America. Yet, nearly 68,000 patients with heart failure and reduced left ventricular ejection fraction (LVEF) die each year in the United States because they do not receive these therapies (Am. Heart J. 2011;161:1024-30).

"If we bridged that gap, and assuming the efficacy and effectiveness match, you can see the potential number of lives saved each year. ... And, in fact, the greatest number of lives saved [roughly 21,400] could result from the improved use of aldosterone antagonists, if there were optimal implementation," he said.

Indeed, analyses show that only about one-third of eligible heart failure outpatients (Circ. Heart Fail. 2008;1:98-106) and inpatients (JAMA 2009;302:1658-65) in real-world U.S. practice receive drugs in this class.

Some resistance to the use of aldosterone antagonists – such as spironolactone (brand name Aldactone) and eplerenone (Inspra) – has stemmed from uncertainty as to whether the risk-benefit profile in clinical trials translates to real-world practice, according to Dr. Fonarow.

A recent analysis suggests that among patients with heart failure and reduced LVEF, aldosterone antagonist therapy decreases the risk of death by about 30% and the risk of hospitalization by 35% (Am. Heart J. 2011;161:1024-30). The number needed to treat to prevent a single death in a 36-month period is just eight, and the benefit is incremental to that of other standard therapies.

"There was just a moderate increase in the risk of hyperkalemia and increased creatinine, but overall, safe and well tolerated," he said. "They were shown to be highly cost effective even with fully branded medications at full cost, and the benefits greatly outweighed the potential risks."

However, an analysis of Canadian administrative data showed that after publication of the Randomized Aldactone Evaluation Study (RALES), which found significant benefit of spironolactone in heart failure, there was an increase in prescriptions for the drug but also a concomitant increase in hyperkalemia-related hospitalizations and deaths (N. Engl. J. Med. 2004;351:543-51).

The analysis did not assess benefits and had some limitations, according to Dr. Fonarow. "But after that publication and a few others, a number of notable heart failure experts stated pretty strong viewpoints that aldosterone antagonists are really not safe in real-world clinical practice, the risks outweigh any potential benefits, and they should be reserved only for the most severe heart failure patients and only after all other therapies have been tried and failed."

Yet, other studies have suggested, for example, that every 10% increase in aldosterone antagonist use among hospitalized patients is associated with a 6% reduction in all-cause mortality over the following year (Am. Heart J. 2010;159:406-13). Furthermore, in the context of careful monitoring, with increasing use of spironolactone, hyperkalemia is not problematic (BMJ 2010;340:c1768).

"Certainly, some of the data have had a number of individuals saying, ‘We need to get away from evidence guidelines and performance measures, and individualize therapy,’ and ‘I should pick and choose therapy as I think,’ and ‘Findings from clinical trials are not applicable to my patients, they are much more complex, and I know my patients are going to do well because I give them highly personalized care rather than cookbook medicine,’" Dr. Fonarow commented. "That is certainly not a very scientific or satisfying type of approach."

Experience from IMPROVE HF suggests that a performance improvement program can safely and effectively increase the use of aldosterone antagonists for heart failure in a real-world setting (Circulation 2010;122:585-96). The program led to a near doubling of use of these agents over 2 years. "At the same time, did we see any increase in inappropriate or ineligible patients being treated? No, the rates for patients with absolute contraindications or relative contraindications was very small, below 1%, and did not increase," he said.

"Treatment gaps between guidelines and practice exist for heart failure and, as a result, large numbers of patients are having hospitalizations and fatal events that could have been prevented. This is particularly true for aldosterone antagonists," Dr. Fonarow concluded. "Bridging the gap between evidence and clinical practice systems is needed, and by applying these evidence-based therapies with the appropriate monitoring and the appropriate selection of patients, we can do this in a way that truly will improve outcomes."

Dr. Fonarow disclosed that he is a consultant to and/or receives honoraria or research funding from Novartis and Medtronic.

SEATTLE – Isolated left ventricular diastolic dysfunction should not be viewed as a reason to withhold ablation therapy in patients with atrial fibrillation and preserved ejection fraction, new data suggest.

Investigators led by Dr. Rosita Zakeri studied a series of 707 patients who were undergoing a first catheter ablation at the Mayo Clinic for symptomatic, drug-refractory atrial fibrillation and who had preserved left ventricular ejection fraction.

Fully 34% had isolated diastolic dysfunction (a left atrial pressure of greater than 15 mm as measured directly by the transseptal approach), according to results reported at the annual meeting of the Heart Failure Society of America.

Patients with isolated diastolic dysfunction had a marginally elevated risk of recurrence of atrial fibrillation at 1 year in a univariate analysis but not after multivariate adjustment. In addition, they derived a similar improvement in quality of life from ablation.

"Although diastolic dysfunction was associated with an increased risk of atrial fibrillation recurrence, in and of itself, it does not appear to be a key arrhythmogenic factor nor strongly related to quality of life at 1 year after ablation," commented Dr. Zakeri, who is a cardiology fellow at the Mayo Clinic in Rochester, Minn.

"Therefore ... the presence of left ventricular diastolic dysfunction should not necessarily discourage the use of catheter ablation for treatment of symptomatic atrial fibrillation in this patient group," she said.

Diastolic dysfunction increases susceptibility to atrial fibrillation, but it is unclear whether it has a continued proarrhythmic effect after ablation, Dr. Zakeri noted.

"We also know that diastolic dysfunction predisposes to heart failure and is one of the hemodynamic hallmarks of heart failure with preserved ejection fraction," she continued. And some patients with atrial fibrillation having diastolic dysfunction may have early heart failure, with the arrhythmia accelerating the severity or presentation of symptoms.

Study results showed that relative to other patients, the patients with isolated diastolic dysfunction had a higher body mass index; had greater prevalences of diabetes, hypertension, and heart failure; were more likely to have nonparoxysmal atrial fibrillation; and had poorer quality of life as assessed with both the Medical Outcomes Study 36-item questionnaire (SF-36) and the Mayo AF-specific Symptom Inventory (MAFSI).

Overall, 21.1% of patients had a recurrence of atrial fibrillation at 1 year, Dr. Zakeri reported. The rate was 25.3% in patients with diastolic dysfunction and 18.9% in patients without it.

The difference corresponded to a marginally elevated risk of recurrence for the group with diastolic dysfunction in unadjusted analyses (odds ratio, 1.45; P = .05), but after adjustment for age, sex, type of atrial fibrillation, and left atrial volume index, there was no significant association.

When patients were stratified by baseline left atrial pressure – less than 12 mm Hg, 12-15 mm Hg, or greater than 15 mm Hg – all three groups had significant improvements at 1 year in scores on the quality of life scales, with no significant difference in the magnitude of improvement between them.

Dr. Zakeri disclosed no relevant conflicts of interest.

SEATTLE – Isolated left ventricular diastolic dysfunction should not be viewed as a reason to withhold ablation therapy in patients with atrial fibrillation and preserved ejection fraction, new data suggest.

Investigators led by Dr. Rosita Zakeri studied a series of 707 patients who were undergoing a first catheter ablation at the Mayo Clinic for symptomatic, drug-refractory atrial fibrillation and who had preserved left ventricular ejection fraction.

Fully 34% had isolated diastolic dysfunction (a left atrial pressure of greater than 15 mm as measured directly by the transseptal approach), according to results reported at the annual meeting of the Heart Failure Society of America.

Patients with isolated diastolic dysfunction had a marginally elevated risk of recurrence of atrial fibrillation at 1 year in a univariate analysis but not after multivariate adjustment. In addition, they derived a similar improvement in quality of life from ablation.

"Although diastolic dysfunction was associated with an increased risk of atrial fibrillation recurrence, in and of itself, it does not appear to be a key arrhythmogenic factor nor strongly related to quality of life at 1 year after ablation," commented Dr. Zakeri, who is a cardiology fellow at the Mayo Clinic in Rochester, Minn.

"Therefore ... the presence of left ventricular diastolic dysfunction should not necessarily discourage the use of catheter ablation for treatment of symptomatic atrial fibrillation in this patient group," she said.

Diastolic dysfunction increases susceptibility to atrial fibrillation, but it is unclear whether it has a continued proarrhythmic effect after ablation, Dr. Zakeri noted.

"We also know that diastolic dysfunction predisposes to heart failure and is one of the hemodynamic hallmarks of heart failure with preserved ejection fraction," she continued. And some patients with atrial fibrillation having diastolic dysfunction may have early heart failure, with the arrhythmia accelerating the severity or presentation of symptoms.

Study results showed that relative to other patients, the patients with isolated diastolic dysfunction had a higher body mass index; had greater prevalences of diabetes, hypertension, and heart failure; were more likely to have nonparoxysmal atrial fibrillation; and had poorer quality of life as assessed with both the Medical Outcomes Study 36-item questionnaire (SF-36) and the Mayo AF-specific Symptom Inventory (MAFSI).

Overall, 21.1% of patients had a recurrence of atrial fibrillation at 1 year, Dr. Zakeri reported. The rate was 25.3% in patients with diastolic dysfunction and 18.9% in patients without it.

The difference corresponded to a marginally elevated risk of recurrence for the group with diastolic dysfunction in unadjusted analyses (odds ratio, 1.45; P = .05), but after adjustment for age, sex, type of atrial fibrillation, and left atrial volume index, there was no significant association.

When patients were stratified by baseline left atrial pressure – less than 12 mm Hg, 12-15 mm Hg, or greater than 15 mm Hg – all three groups had significant improvements at 1 year in scores on the quality of life scales, with no significant difference in the magnitude of improvement between them.

Dr. Zakeri disclosed no relevant conflicts of interest.

SEATTLE – Isolated left ventricular diastolic dysfunction should not be viewed as a reason to withhold ablation therapy in patients with atrial fibrillation and preserved ejection fraction, new data suggest.

Investigators led by Dr. Rosita Zakeri studied a series of 707 patients who were undergoing a first catheter ablation at the Mayo Clinic for symptomatic, drug-refractory atrial fibrillation and who had preserved left ventricular ejection fraction.

Fully 34% had isolated diastolic dysfunction (a left atrial pressure of greater than 15 mm as measured directly by the transseptal approach), according to results reported at the annual meeting of the Heart Failure Society of America.

Patients with isolated diastolic dysfunction had a marginally elevated risk of recurrence of atrial fibrillation at 1 year in a univariate analysis but not after multivariate adjustment. In addition, they derived a similar improvement in quality of life from ablation.

"Although diastolic dysfunction was associated with an increased risk of atrial fibrillation recurrence, in and of itself, it does not appear to be a key arrhythmogenic factor nor strongly related to quality of life at 1 year after ablation," commented Dr. Zakeri, who is a cardiology fellow at the Mayo Clinic in Rochester, Minn.

"Therefore ... the presence of left ventricular diastolic dysfunction should not necessarily discourage the use of catheter ablation for treatment of symptomatic atrial fibrillation in this patient group," she said.

Diastolic dysfunction increases susceptibility to atrial fibrillation, but it is unclear whether it has a continued proarrhythmic effect after ablation, Dr. Zakeri noted.

"We also know that diastolic dysfunction predisposes to heart failure and is one of the hemodynamic hallmarks of heart failure with preserved ejection fraction," she continued. And some patients with atrial fibrillation having diastolic dysfunction may have early heart failure, with the arrhythmia accelerating the severity or presentation of symptoms.

Study results showed that relative to other patients, the patients with isolated diastolic dysfunction had a higher body mass index; had greater prevalences of diabetes, hypertension, and heart failure; were more likely to have nonparoxysmal atrial fibrillation; and had poorer quality of life as assessed with both the Medical Outcomes Study 36-item questionnaire (SF-36) and the Mayo AF-specific Symptom Inventory (MAFSI).

Overall, 21.1% of patients had a recurrence of atrial fibrillation at 1 year, Dr. Zakeri reported. The rate was 25.3% in patients with diastolic dysfunction and 18.9% in patients without it.

The difference corresponded to a marginally elevated risk of recurrence for the group with diastolic dysfunction in unadjusted analyses (odds ratio, 1.45; P = .05), but after adjustment for age, sex, type of atrial fibrillation, and left atrial volume index, there was no significant association.

When patients were stratified by baseline left atrial pressure – less than 12 mm Hg, 12-15 mm Hg, or greater than 15 mm Hg – all three groups had significant improvements at 1 year in scores on the quality of life scales, with no significant difference in the magnitude of improvement between them.

Dr. Zakeri disclosed no relevant conflicts of interest.

SEATTLE – Patients with heart failure still benefit from spironolactone therapy even when they develop elevated potassium levels, a well-known and potentially life-threatening side effect of the medication, new data suggest.

Investigators led by Orly Vardeny, Pharm.D., conducted a secondary analysis of data from the RALES (Randomized Aldactone Evaluation Study) trial, in which more than 1,500 patients with heart failure were assigned to spironolactone (Aldactone) or placebo.

The spironolactone group had nearly quadruple the risk of hyperkalemia compared with the placebo group, she reported at the annual meeting of the Heart Failure Society of America. And hyperkalemia was indeed associated with a higher mortality rate.

But relative to their placebo-treated counterparts who did not have elevated potassium levels, spironolactone-treated patients who had elevated potassium levels, up to a serum potassium level of at least 5.5 mEq/L, were still less likely to die.

"The benefits of spironolactone are maintained in patients with mild to moderate hyperkalemia, and even in patients with potassium levels approaching 6.0 mEq/L," commented Dr. Vardeny, who is an associate professor of pharmacy at the University of Wisconsin in Madison.

"Our data argue for strategies that maintain spironolactone or aldosterone antagonist therapy even in the setting of mild to moderate hyperkalemia," she maintained.

"How many of these patients were on digoxin, and did you factor that into the analysis?" asked session comoderator Dr. Carl V. Leier of the Ohio State University Medical Center in Columbus.

Dr. Vardeny replied that analyses did not adjust for digoxin use, but they did adjust for age, estimated glomerular filtration rate, baseline potassium level, and diabetes.

"It seems that hypokalemia was more dangerous than hyperkalemia," commented attendee Dr. Edward Gilbert of the University of Utah in Salt Lake City. Might some of the benefit of spironolactone actually be related to reduced hypokalemia, he wondered.

"My personal bias is that there could be an association. This is really difficult to prove, only because potassium will vary so much, so the data will inform multiple categories of potassium," Dr. Vardeny replied. "But yes, we are investigating that as well."

The 1,663 patients in RALES had moderate to severe heart failure with a left ventricular ejection fraction of less than 35%, and were already receiving an angiotensin-converting enzyme inhibitor with or without a diuretic. They were randomized evenly to 25 mg of spironolactone daily, with optional titration up to 50 mg daily or placebo.

Serum potassium levels were monitored regularly. If patients developed hyperkalemia, investigators could reduce the dose of study medication but were encouraged to first adjust doses of other medications.

Main RALES results, previously reported, showed that spironolactone treatment was associated with a 30% reduction in the risk of all-cause mortality and a 35% reduction in the risk of hospitalization for worsening of heart failure (N. Engl. J. Med. 1999;341:709-17).

The new analysis showed that both treatment groups had mean potassium levels of 4.3 mEq/L at baseline. But levels increased within the first month in the spironolactone group and remained persistently higher than those in the placebo group, by 0.25 mEq/L on average, throughout the trial.

Relative to their peers in the placebo group, patients in the spironolactone group were significantly less likely to develop hypokalemia (6.5% vs. 16.2%) and more likely to develop hyperkalemia (14.5% vs. 4.2%), Dr. Vardeny reported. Hypokalemia was defined as a potassium level of less than 3.5 mEq/L; hyperkalemia equalled a potassium level of greater than 5.5 mEq/L.

In the spironolactone group, the rate of death was fairly stable – at about 17 per 100 patient-years – for patients with potassium levels ranging from 3.5 to 6.0 mEq/L. But it was higher among patients with lower levels (about 42 per 100 patient-years) or higher levels (about 25 per 100 patient-years).

In a multivariate analysis, patients were more likely to develop hypokalemia if they were black (hazard ratio, 2.0) or had a higher New York Heart Association functional class (HR, 1.5), whereas they were less likely if they had a higher baseline potassium level (HR, 0.25) or received spironolactone (HR, 0.36).

Patients were more likely to develop hyperkalemia if they received spironolactone (HR, 3.7), had a higher baseline potassium level (HR, 2.4), or had a history of diabetes (HR, 1.9).

Compared with placebo-treated patients having potassium levels of less than 5.0 mEq/L, spironolactone-treated patients with elevated potassium levels still had a significantly lower risk of death with potassium levels up to 5.5 mEq/L, and they had a nonsignificantly lower risk with levels up to about 6.0 mEq/L.

Dr. Vardeny reported having no relevant conflicts of interest. The RALES trial was sponsored by Searle, manufacturer of Aldactone.

SEATTLE – Patients with heart failure still benefit from spironolactone therapy even when they develop elevated potassium levels, a well-known and potentially life-threatening side effect of the medication, new data suggest.

Investigators led by Orly Vardeny, Pharm.D., conducted a secondary analysis of data from the RALES (Randomized Aldactone Evaluation Study) trial, in which more than 1,500 patients with heart failure were assigned to spironolactone (Aldactone) or placebo.

The spironolactone group had nearly quadruple the risk of hyperkalemia compared with the placebo group, she reported at the annual meeting of the Heart Failure Society of America. And hyperkalemia was indeed associated with a higher mortality rate.

But relative to their placebo-treated counterparts who did not have elevated potassium levels, spironolactone-treated patients who had elevated potassium levels, up to a serum potassium level of at least 5.5 mEq/L, were still less likely to die.

"The benefits of spironolactone are maintained in patients with mild to moderate hyperkalemia, and even in patients with potassium levels approaching 6.0 mEq/L," commented Dr. Vardeny, who is an associate professor of pharmacy at the University of Wisconsin in Madison.

"Our data argue for strategies that maintain spironolactone or aldosterone antagonist therapy even in the setting of mild to moderate hyperkalemia," she maintained.

"How many of these patients were on digoxin, and did you factor that into the analysis?" asked session comoderator Dr. Carl V. Leier of the Ohio State University Medical Center in Columbus.

Dr. Vardeny replied that analyses did not adjust for digoxin use, but they did adjust for age, estimated glomerular filtration rate, baseline potassium level, and diabetes.

"It seems that hypokalemia was more dangerous than hyperkalemia," commented attendee Dr. Edward Gilbert of the University of Utah in Salt Lake City. Might some of the benefit of spironolactone actually be related to reduced hypokalemia, he wondered.

"My personal bias is that there could be an association. This is really difficult to prove, only because potassium will vary so much, so the data will inform multiple categories of potassium," Dr. Vardeny replied. "But yes, we are investigating that as well."

The 1,663 patients in RALES had moderate to severe heart failure with a left ventricular ejection fraction of less than 35%, and were already receiving an angiotensin-converting enzyme inhibitor with or without a diuretic. They were randomized evenly to 25 mg of spironolactone daily, with optional titration up to 50 mg daily or placebo.

Serum potassium levels were monitored regularly. If patients developed hyperkalemia, investigators could reduce the dose of study medication but were encouraged to first adjust doses of other medications.

Main RALES results, previously reported, showed that spironolactone treatment was associated with a 30% reduction in the risk of all-cause mortality and a 35% reduction in the risk of hospitalization for worsening of heart failure (N. Engl. J. Med. 1999;341:709-17).

The new analysis showed that both treatment groups had mean potassium levels of 4.3 mEq/L at baseline. But levels increased within the first month in the spironolactone group and remained persistently higher than those in the placebo group, by 0.25 mEq/L on average, throughout the trial.

Relative to their peers in the placebo group, patients in the spironolactone group were significantly less likely to develop hypokalemia (6.5% vs. 16.2%) and more likely to develop hyperkalemia (14.5% vs. 4.2%), Dr. Vardeny reported. Hypokalemia was defined as a potassium level of less than 3.5 mEq/L; hyperkalemia equalled a potassium level of greater than 5.5 mEq/L.

In the spironolactone group, the rate of death was fairly stable – at about 17 per 100 patient-years – for patients with potassium levels ranging from 3.5 to 6.0 mEq/L. But it was higher among patients with lower levels (about 42 per 100 patient-years) or higher levels (about 25 per 100 patient-years).

In a multivariate analysis, patients were more likely to develop hypokalemia if they were black (hazard ratio, 2.0) or had a higher New York Heart Association functional class (HR, 1.5), whereas they were less likely if they had a higher baseline potassium level (HR, 0.25) or received spironolactone (HR, 0.36).

Patients were more likely to develop hyperkalemia if they received spironolactone (HR, 3.7), had a higher baseline potassium level (HR, 2.4), or had a history of diabetes (HR, 1.9).

Compared with placebo-treated patients having potassium levels of less than 5.0 mEq/L, spironolactone-treated patients with elevated potassium levels still had a significantly lower risk of death with potassium levels up to 5.5 mEq/L, and they had a nonsignificantly lower risk with levels up to about 6.0 mEq/L.

Dr. Vardeny reported having no relevant conflicts of interest. The RALES trial was sponsored by Searle, manufacturer of Aldactone.

SEATTLE – Patients with heart failure still benefit from spironolactone therapy even when they develop elevated potassium levels, a well-known and potentially life-threatening side effect of the medication, new data suggest.

Investigators led by Orly Vardeny, Pharm.D., conducted a secondary analysis of data from the RALES (Randomized Aldactone Evaluation Study) trial, in which more than 1,500 patients with heart failure were assigned to spironolactone (Aldactone) or placebo.

The spironolactone group had nearly quadruple the risk of hyperkalemia compared with the placebo group, she reported at the annual meeting of the Heart Failure Society of America. And hyperkalemia was indeed associated with a higher mortality rate.

But relative to their placebo-treated counterparts who did not have elevated potassium levels, spironolactone-treated patients who had elevated potassium levels, up to a serum potassium level of at least 5.5 mEq/L, were still less likely to die.

"The benefits of spironolactone are maintained in patients with mild to moderate hyperkalemia, and even in patients with potassium levels approaching 6.0 mEq/L," commented Dr. Vardeny, who is an associate professor of pharmacy at the University of Wisconsin in Madison.

"Our data argue for strategies that maintain spironolactone or aldosterone antagonist therapy even in the setting of mild to moderate hyperkalemia," she maintained.

"How many of these patients were on digoxin, and did you factor that into the analysis?" asked session comoderator Dr. Carl V. Leier of the Ohio State University Medical Center in Columbus.

Dr. Vardeny replied that analyses did not adjust for digoxin use, but they did adjust for age, estimated glomerular filtration rate, baseline potassium level, and diabetes.

"It seems that hypokalemia was more dangerous than hyperkalemia," commented attendee Dr. Edward Gilbert of the University of Utah in Salt Lake City. Might some of the benefit of spironolactone actually be related to reduced hypokalemia, he wondered.

"My personal bias is that there could be an association. This is really difficult to prove, only because potassium will vary so much, so the data will inform multiple categories of potassium," Dr. Vardeny replied. "But yes, we are investigating that as well."

The 1,663 patients in RALES had moderate to severe heart failure with a left ventricular ejection fraction of less than 35%, and were already receiving an angiotensin-converting enzyme inhibitor with or without a diuretic. They were randomized evenly to 25 mg of spironolactone daily, with optional titration up to 50 mg daily or placebo.

Serum potassium levels were monitored regularly. If patients developed hyperkalemia, investigators could reduce the dose of study medication but were encouraged to first adjust doses of other medications.

Main RALES results, previously reported, showed that spironolactone treatment was associated with a 30% reduction in the risk of all-cause mortality and a 35% reduction in the risk of hospitalization for worsening of heart failure (N. Engl. J. Med. 1999;341:709-17).

The new analysis showed that both treatment groups had mean potassium levels of 4.3 mEq/L at baseline. But levels increased within the first month in the spironolactone group and remained persistently higher than those in the placebo group, by 0.25 mEq/L on average, throughout the trial.

Relative to their peers in the placebo group, patients in the spironolactone group were significantly less likely to develop hypokalemia (6.5% vs. 16.2%) and more likely to develop hyperkalemia (14.5% vs. 4.2%), Dr. Vardeny reported. Hypokalemia was defined as a potassium level of less than 3.5 mEq/L; hyperkalemia equalled a potassium level of greater than 5.5 mEq/L.

In the spironolactone group, the rate of death was fairly stable – at about 17 per 100 patient-years – for patients with potassium levels ranging from 3.5 to 6.0 mEq/L. But it was higher among patients with lower levels (about 42 per 100 patient-years) or higher levels (about 25 per 100 patient-years).

In a multivariate analysis, patients were more likely to develop hypokalemia if they were black (hazard ratio, 2.0) or had a higher New York Heart Association functional class (HR, 1.5), whereas they were less likely if they had a higher baseline potassium level (HR, 0.25) or received spironolactone (HR, 0.36).

Patients were more likely to develop hyperkalemia if they received spironolactone (HR, 3.7), had a higher baseline potassium level (HR, 2.4), or had a history of diabetes (HR, 1.9).

Compared with placebo-treated patients having potassium levels of less than 5.0 mEq/L, spironolactone-treated patients with elevated potassium levels still had a significantly lower risk of death with potassium levels up to 5.5 mEq/L, and they had a nonsignificantly lower risk with levels up to about 6.0 mEq/L.

Dr. Vardeny reported having no relevant conflicts of interest. The RALES trial was sponsored by Searle, manufacturer of Aldactone.

SEATTLE – A brief cognitive biobehavioral intervention focused on preventing and managing depression reduces adverse outcomes of heart failure, according to results from a randomized trial reported at the annual meeting of the Heart Failure Society of America.

"A 6-week biobehavioral intervention in patients with heart failure really was successful in severing the link between depression and poor outcomes," according to the study’s lead investigator, Debra K. Moser, D.N.Sc., professor and chair of the College of Nursing at the University of Kentucky, Lexington. "These findings provide evidence for the effectiveness of biobehavioral approaches" in this population.

Dr. Moser also noted that more than one-fifth of patients with heart failure have depression, as well as higher depressive symptoms – not necessarily clinical depression. Evidence suggests that in the heart failure population, such symptoms triple the risk of rehospitalization and double the risk of death (J. Am. Coll. Cardiol. 2006;48:1527-37).

Dr. Moser and her colleagues studied 278 patients with heart failure, assigning them to a biobehavioral intervention group (given both cognitive-behavioral therapy and biofeedback-relaxation therapy), an attention control group, or a usual-care control group. At baseline, patients were an average of 60 years old, roughly a third were women, and nearly half had New York Heart Association class III or IV heart failure. Mean depression scores on the 27-point Patient Health Questionnaire-9 were about 5.5; one-fourth of patients were taking antidepressants. Patients with heart failure were eligible for the trial if they had been on stable medication doses for at least 1 month, had not experienced a myocardial infarction or stroke in the previous 3 months, and did not have any cognitive impairment.

At 12 months’ follow-up, the biobehavioral intervention patients were about one-third less likely to have had a cardiac hospitalization or to die (28%) compared with the attention control group (40%) and the usual-care control group (38%).

Patients in the biobehavioral intervention group also had an improvement at 1 year in scores for health-related quality of life, measured with the Minnesota Living with Heart Failure questionnaire, whereas scores worsened in the other groups (P = .005).

Similarly, patients in the biobehavioral intervention group had an improvement at 1 year in scores for depression symptoms, whereas scores worsened in the other groups (P = .001). Some 13% of patients in the biobehavioral intervention group had depression at this time point, compared with 21% of those in the attention control group and 24% of those in the usual-care control group.

The biobehavioral intervention lasted 6 weeks, and consisted of 1-hour weekly sessions conducted by a therapist; it was designed to address depression and comorbid anxiety. "The therapist was a psychiatric nurse practitioner with extensive cardiac experience, and she was well suited to this project because she is from the part of Kentucky where many of the patients come from, so ... there is a lot of concordance between her style and her patients’," Dr. Moser explained.

The attention control condition also lasted 6 weeks, and consisted of 1-hour weekly sessions with the same nurse practitioner present, but entailed only unguided relaxation and the opportunity to speak with her.

Christine Moravec, Ph.D., of the Cleveland Clinic, pointed out that at this point it’s difficult to dissect out whether the benefits seen in the biobehavioral intervention were due to the cognitive-behavioral therapy or the biofeedback.

"That’s our next trial" Dr. Moser noted. "We will be looking at the combination of the two and [each] separately."

Reproducibility is another issue, noted Dr. Javed Butler of Emory University in Atlanta. "Can anybody who does this biobehavioral intervention expect the same results?"

"That’s actually the major question that I have," Dr. Moser acknowledged. The particular nurse practitioner who ran the biobehavioral intervention "is probably the best therapist for these people that I have ever seen, so I really do worry about the reproducibility.

"But also, it sort of speaks to maybe some of the failure of the other clinical trials that we have seen in treating depression for cardiac patients. We have had some colossal failures," she continued. "I don’t think that any therapist can do it. It takes a special therapist who can really connect with patients, and a lot of patients, who can individualize therapy and is concordant with the group. ... The negative impact of depression is so powerful that it bears looking at to try to really define what it is in the therapist-patient relationship that is important and that does need to be reproduced."

Interestingly, depression levels in the biobehavioral intervention group continued to decline over a year, whereas they increased in the control groups, according to Dr. Moser. "We think that that is how cognitive-behavioral therapy should work. It doesn’t of course work for everyone, but if it works, it should give you the skills to manage depressive symptoms in the long term," she said.

"Future research should examine the combined effects of pharmacological and biobehavioral therapy, and ... we need to think about the practicality of this intensive intervention in widespread clinical practice," she added.

Dr. Moser reported having no relevant conflicts of interest.

SEATTLE – A brief cognitive biobehavioral intervention focused on preventing and managing depression reduces adverse outcomes of heart failure, according to results from a randomized trial reported at the annual meeting of the Heart Failure Society of America.

"A 6-week biobehavioral intervention in patients with heart failure really was successful in severing the link between depression and poor outcomes," according to the study’s lead investigator, Debra K. Moser, D.N.Sc., professor and chair of the College of Nursing at the University of Kentucky, Lexington. "These findings provide evidence for the effectiveness of biobehavioral approaches" in this population.

Dr. Moser also noted that more than one-fifth of patients with heart failure have depression, as well as higher depressive symptoms – not necessarily clinical depression. Evidence suggests that in the heart failure population, such symptoms triple the risk of rehospitalization and double the risk of death (J. Am. Coll. Cardiol. 2006;48:1527-37).

Dr. Moser and her colleagues studied 278 patients with heart failure, assigning them to a biobehavioral intervention group (given both cognitive-behavioral therapy and biofeedback-relaxation therapy), an attention control group, or a usual-care control group. At baseline, patients were an average of 60 years old, roughly a third were women, and nearly half had New York Heart Association class III or IV heart failure. Mean depression scores on the 27-point Patient Health Questionnaire-9 were about 5.5; one-fourth of patients were taking antidepressants. Patients with heart failure were eligible for the trial if they had been on stable medication doses for at least 1 month, had not experienced a myocardial infarction or stroke in the previous 3 months, and did not have any cognitive impairment.

At 12 months’ follow-up, the biobehavioral intervention patients were about one-third less likely to have had a cardiac hospitalization or to die (28%) compared with the attention control group (40%) and the usual-care control group (38%).

Patients in the biobehavioral intervention group also had an improvement at 1 year in scores for health-related quality of life, measured with the Minnesota Living with Heart Failure questionnaire, whereas scores worsened in the other groups (P = .005).

Similarly, patients in the biobehavioral intervention group had an improvement at 1 year in scores for depression symptoms, whereas scores worsened in the other groups (P = .001). Some 13% of patients in the biobehavioral intervention group had depression at this time point, compared with 21% of those in the attention control group and 24% of those in the usual-care control group.

The biobehavioral intervention lasted 6 weeks, and consisted of 1-hour weekly sessions conducted by a therapist; it was designed to address depression and comorbid anxiety. "The therapist was a psychiatric nurse practitioner with extensive cardiac experience, and she was well suited to this project because she is from the part of Kentucky where many of the patients come from, so ... there is a lot of concordance between her style and her patients’," Dr. Moser explained.

The attention control condition also lasted 6 weeks, and consisted of 1-hour weekly sessions with the same nurse practitioner present, but entailed only unguided relaxation and the opportunity to speak with her.

Christine Moravec, Ph.D., of the Cleveland Clinic, pointed out that at this point it’s difficult to dissect out whether the benefits seen in the biobehavioral intervention were due to the cognitive-behavioral therapy or the biofeedback.

"That’s our next trial" Dr. Moser noted. "We will be looking at the combination of the two and [each] separately."

Reproducibility is another issue, noted Dr. Javed Butler of Emory University in Atlanta. "Can anybody who does this biobehavioral intervention expect the same results?"

"That’s actually the major question that I have," Dr. Moser acknowledged. The particular nurse practitioner who ran the biobehavioral intervention "is probably the best therapist for these people that I have ever seen, so I really do worry about the reproducibility.

"But also, it sort of speaks to maybe some of the failure of the other clinical trials that we have seen in treating depression for cardiac patients. We have had some colossal failures," she continued. "I don’t think that any therapist can do it. It takes a special therapist who can really connect with patients, and a lot of patients, who can individualize therapy and is concordant with the group. ... The negative impact of depression is so powerful that it bears looking at to try to really define what it is in the therapist-patient relationship that is important and that does need to be reproduced."

Interestingly, depression levels in the biobehavioral intervention group continued to decline over a year, whereas they increased in the control groups, according to Dr. Moser. "We think that that is how cognitive-behavioral therapy should work. It doesn’t of course work for everyone, but if it works, it should give you the skills to manage depressive symptoms in the long term," she said.

"Future research should examine the combined effects of pharmacological and biobehavioral therapy, and ... we need to think about the practicality of this intensive intervention in widespread clinical practice," she added.

Dr. Moser reported having no relevant conflicts of interest.

SEATTLE – A brief cognitive biobehavioral intervention focused on preventing and managing depression reduces adverse outcomes of heart failure, according to results from a randomized trial reported at the annual meeting of the Heart Failure Society of America.

"A 6-week biobehavioral intervention in patients with heart failure really was successful in severing the link between depression and poor outcomes," according to the study’s lead investigator, Debra K. Moser, D.N.Sc., professor and chair of the College of Nursing at the University of Kentucky, Lexington. "These findings provide evidence for the effectiveness of biobehavioral approaches" in this population.

Dr. Moser also noted that more than one-fifth of patients with heart failure have depression, as well as higher depressive symptoms – not necessarily clinical depression. Evidence suggests that in the heart failure population, such symptoms triple the risk of rehospitalization and double the risk of death (J. Am. Coll. Cardiol. 2006;48:1527-37).

Dr. Moser and her colleagues studied 278 patients with heart failure, assigning them to a biobehavioral intervention group (given both cognitive-behavioral therapy and biofeedback-relaxation therapy), an attention control group, or a usual-care control group. At baseline, patients were an average of 60 years old, roughly a third were women, and nearly half had New York Heart Association class III or IV heart failure. Mean depression scores on the 27-point Patient Health Questionnaire-9 were about 5.5; one-fourth of patients were taking antidepressants. Patients with heart failure were eligible for the trial if they had been on stable medication doses for at least 1 month, had not experienced a myocardial infarction or stroke in the previous 3 months, and did not have any cognitive impairment.

At 12 months’ follow-up, the biobehavioral intervention patients were about one-third less likely to have had a cardiac hospitalization or to die (28%) compared with the attention control group (40%) and the usual-care control group (38%).

Patients in the biobehavioral intervention group also had an improvement at 1 year in scores for health-related quality of life, measured with the Minnesota Living with Heart Failure questionnaire, whereas scores worsened in the other groups (P = .005).

Similarly, patients in the biobehavioral intervention group had an improvement at 1 year in scores for depression symptoms, whereas scores worsened in the other groups (P = .001). Some 13% of patients in the biobehavioral intervention group had depression at this time point, compared with 21% of those in the attention control group and 24% of those in the usual-care control group.

The biobehavioral intervention lasted 6 weeks, and consisted of 1-hour weekly sessions conducted by a therapist; it was designed to address depression and comorbid anxiety. "The therapist was a psychiatric nurse practitioner with extensive cardiac experience, and she was well suited to this project because she is from the part of Kentucky where many of the patients come from, so ... there is a lot of concordance between her style and her patients’," Dr. Moser explained.

The attention control condition also lasted 6 weeks, and consisted of 1-hour weekly sessions with the same nurse practitioner present, but entailed only unguided relaxation and the opportunity to speak with her.

Christine Moravec, Ph.D., of the Cleveland Clinic, pointed out that at this point it’s difficult to dissect out whether the benefits seen in the biobehavioral intervention were due to the cognitive-behavioral therapy or the biofeedback.

"That’s our next trial" Dr. Moser noted. "We will be looking at the combination of the two and [each] separately."

Reproducibility is another issue, noted Dr. Javed Butler of Emory University in Atlanta. "Can anybody who does this biobehavioral intervention expect the same results?"

"That’s actually the major question that I have," Dr. Moser acknowledged. The particular nurse practitioner who ran the biobehavioral intervention "is probably the best therapist for these people that I have ever seen, so I really do worry about the reproducibility.

"But also, it sort of speaks to maybe some of the failure of the other clinical trials that we have seen in treating depression for cardiac patients. We have had some colossal failures," she continued. "I don’t think that any therapist can do it. It takes a special therapist who can really connect with patients, and a lot of patients, who can individualize therapy and is concordant with the group. ... The negative impact of depression is so powerful that it bears looking at to try to really define what it is in the therapist-patient relationship that is important and that does need to be reproduced."

Interestingly, depression levels in the biobehavioral intervention group continued to decline over a year, whereas they increased in the control groups, according to Dr. Moser. "We think that that is how cognitive-behavioral therapy should work. It doesn’t of course work for everyone, but if it works, it should give you the skills to manage depressive symptoms in the long term," she said.

"Future research should examine the combined effects of pharmacological and biobehavioral therapy, and ... we need to think about the practicality of this intensive intervention in widespread clinical practice," she added.

Dr. Moser reported having no relevant conflicts of interest.