Heart Failure

NEW ORLEANS – Myocardial viability failed to predict a significant survival benefit from coronary bypass surgery in patients with coronary artery disease and left ventricular dysfunction in the STICH Viability substudy.

The data are surprising and call into question the long-standing practice of assessing myocardial viability as a means to predict clinical benefit from coronary bypass surgery.

The substudy included 610 of the 1,212 patients in the Surgical Treatment for Ischemic Heart Failure (STICH) trial who underwent baseline myocardial viability testing using SPECT or dobutamine echocardiography, or both, and were randomly assigned to aggressive medical therapy with or without coronary artery bypass surgery (CABG).

At a median follow-up of 5 years, 51% of patients without viable myocardium and 37% with viable myocardium died. The presence of viable myocardium significantly reduced the risk of all-cause mortality by 36%, but the survival advantage lost statistical significance in a multivariable analysis that included other prognostic variables, Dr. Robert Bonow reported at the annual meeting of the American College of Cardiology.

The secondary outcome of cardiovascular mortality was also significantly lower in patients with myocardial viability compared with those without myocardial viability, at 29% and 43%, respectively, but once again, the association lost significance in multivariable analysis.

Notably, the secondary composite end point of death plus cardiovascular hospitalization, which is commonly used in heart failure trials, retained significance in multivariable analysis in favor of patients with myocardial viability, occurring in 63% of patients with viable myocardium and 82% of those without.

There was no significant interaction, however, between myocardial viability status and medical versus surgical treatment with respect to mortality, whether assessed according to treatment assigned or to the treatment actually received, said Dr. Bonow, professor of cardiology at Northwestern University in Chicago. Five-year all-cause mortality rates among the 114 patients without myocardial viability were 56% with medical therapy and 42% with CABG. Among the 487 patients with myocardial viability the rates were 35% vs. 31%, respectively.

"The lack of interaction between myocardial viability and benefit from CABG in this study indicates that assessment of myocardial viability, independent of other relevant variables, should not be the deciding factor in selecting the best therapy for patients with ischemic left ventricular function," he said.

Discussant Bernard Gersh, professor of medicine at Mayo Clinic in Rochester, Minn., asked what clinicians should analyze to determine which of their patients with heart failure and coronary disease to send to surgery, particularly in light of the benefits observed with CABG in the primary STICH analysis. Those data showed a 5% reduction in all-cause mortality at 6 years with the addition of CABG to medical therapy.

Dr. Bonow replied, "I think viability may be something you look at in some patients, but the point would be that there are other clinical variables, perhaps coronary anatomy, that one would bring into play."

Dr. Steven Bollings, with the Cardiovascular Center at the University of Michigan in Ann Arbor, said the primary STICH results provide a clear answer that patients with heart failure and left ventricular dysfunction benefit from coronary bypass surgery, but that the viability substudy raises a number of questions. He said that myocardial "may not be the No. 1 criterion by which we send patients to the operating room" and that other variables such as whether the patient has clear distal targets or is robust may be more important.

Dr. Gregg W. Stone of Columbia University, New York, said, "While I admit this is the clearly the best and most important viability study ever done, I don’t know that it definitively answers the question for us that viability doesn’t matter."

He pointed out that the viability data were based on only half of the STICH participants, the subsets were unbalanced with 80% of patients having viable myocardium and that some would say it’s not appropriate to look for interaction testing off of a negative end point.

"What I take away from this is that if there’s viability, I really want to be sure to revascularize," said Dr. Ted E. Feldman of NorthShore University HealthSystem in Evanston, Ill. "But prior to seeing these results, I was inclined to say if there wasn’t viability, not to vascularize. And the results of the trial challenge that historic bias," he added.

STICH Viability was supported by grants from the National Heart, Lung, and Blood Institute and Abbott Laboratories. Dr. Bonow had no relevant disclosures.

NEW ORLEANS – Myocardial viability failed to predict a significant survival benefit from coronary bypass surgery in patients with coronary artery disease and left ventricular dysfunction in the STICH Viability substudy.

The data are surprising and call into question the long-standing practice of assessing myocardial viability as a means to predict clinical benefit from coronary bypass surgery.

The substudy included 610 of the 1,212 patients in the Surgical Treatment for Ischemic Heart Failure (STICH) trial who underwent baseline myocardial viability testing using SPECT or dobutamine echocardiography, or both, and were randomly assigned to aggressive medical therapy with or without coronary artery bypass surgery (CABG).

At a median follow-up of 5 years, 51% of patients without viable myocardium and 37% with viable myocardium died. The presence of viable myocardium significantly reduced the risk of all-cause mortality by 36%, but the survival advantage lost statistical significance in a multivariable analysis that included other prognostic variables, Dr. Robert Bonow reported at the annual meeting of the American College of Cardiology.

The secondary outcome of cardiovascular mortality was also significantly lower in patients with myocardial viability compared with those without myocardial viability, at 29% and 43%, respectively, but once again, the association lost significance in multivariable analysis.

Notably, the secondary composite end point of death plus cardiovascular hospitalization, which is commonly used in heart failure trials, retained significance in multivariable analysis in favor of patients with myocardial viability, occurring in 63% of patients with viable myocardium and 82% of those without.

There was no significant interaction, however, between myocardial viability status and medical versus surgical treatment with respect to mortality, whether assessed according to treatment assigned or to the treatment actually received, said Dr. Bonow, professor of cardiology at Northwestern University in Chicago. Five-year all-cause mortality rates among the 114 patients without myocardial viability were 56% with medical therapy and 42% with CABG. Among the 487 patients with myocardial viability the rates were 35% vs. 31%, respectively.

"The lack of interaction between myocardial viability and benefit from CABG in this study indicates that assessment of myocardial viability, independent of other relevant variables, should not be the deciding factor in selecting the best therapy for patients with ischemic left ventricular function," he said.

Discussant Bernard Gersh, professor of medicine at Mayo Clinic in Rochester, Minn., asked what clinicians should analyze to determine which of their patients with heart failure and coronary disease to send to surgery, particularly in light of the benefits observed with CABG in the primary STICH analysis. Those data showed a 5% reduction in all-cause mortality at 6 years with the addition of CABG to medical therapy.

Dr. Bonow replied, "I think viability may be something you look at in some patients, but the point would be that there are other clinical variables, perhaps coronary anatomy, that one would bring into play."

Dr. Steven Bollings, with the Cardiovascular Center at the University of Michigan in Ann Arbor, said the primary STICH results provide a clear answer that patients with heart failure and left ventricular dysfunction benefit from coronary bypass surgery, but that the viability substudy raises a number of questions. He said that myocardial "may not be the No. 1 criterion by which we send patients to the operating room" and that other variables such as whether the patient has clear distal targets or is robust may be more important.

Dr. Gregg W. Stone of Columbia University, New York, said, "While I admit this is the clearly the best and most important viability study ever done, I don’t know that it definitively answers the question for us that viability doesn’t matter."

He pointed out that the viability data were based on only half of the STICH participants, the subsets were unbalanced with 80% of patients having viable myocardium and that some would say it’s not appropriate to look for interaction testing off of a negative end point.

"What I take away from this is that if there’s viability, I really want to be sure to revascularize," said Dr. Ted E. Feldman of NorthShore University HealthSystem in Evanston, Ill. "But prior to seeing these results, I was inclined to say if there wasn’t viability, not to vascularize. And the results of the trial challenge that historic bias," he added.

STICH Viability was supported by grants from the National Heart, Lung, and Blood Institute and Abbott Laboratories. Dr. Bonow had no relevant disclosures.

NEW ORLEANS – Myocardial viability failed to predict a significant survival benefit from coronary bypass surgery in patients with coronary artery disease and left ventricular dysfunction in the STICH Viability substudy.

The data are surprising and call into question the long-standing practice of assessing myocardial viability as a means to predict clinical benefit from coronary bypass surgery.

The substudy included 610 of the 1,212 patients in the Surgical Treatment for Ischemic Heart Failure (STICH) trial who underwent baseline myocardial viability testing using SPECT or dobutamine echocardiography, or both, and were randomly assigned to aggressive medical therapy with or without coronary artery bypass surgery (CABG).

At a median follow-up of 5 years, 51% of patients without viable myocardium and 37% with viable myocardium died. The presence of viable myocardium significantly reduced the risk of all-cause mortality by 36%, but the survival advantage lost statistical significance in a multivariable analysis that included other prognostic variables, Dr. Robert Bonow reported at the annual meeting of the American College of Cardiology.

The secondary outcome of cardiovascular mortality was also significantly lower in patients with myocardial viability compared with those without myocardial viability, at 29% and 43%, respectively, but once again, the association lost significance in multivariable analysis.

Notably, the secondary composite end point of death plus cardiovascular hospitalization, which is commonly used in heart failure trials, retained significance in multivariable analysis in favor of patients with myocardial viability, occurring in 63% of patients with viable myocardium and 82% of those without.

There was no significant interaction, however, between myocardial viability status and medical versus surgical treatment with respect to mortality, whether assessed according to treatment assigned or to the treatment actually received, said Dr. Bonow, professor of cardiology at Northwestern University in Chicago. Five-year all-cause mortality rates among the 114 patients without myocardial viability were 56% with medical therapy and 42% with CABG. Among the 487 patients with myocardial viability the rates were 35% vs. 31%, respectively.

"The lack of interaction between myocardial viability and benefit from CABG in this study indicates that assessment of myocardial viability, independent of other relevant variables, should not be the deciding factor in selecting the best therapy for patients with ischemic left ventricular function," he said.

Discussant Bernard Gersh, professor of medicine at Mayo Clinic in Rochester, Minn., asked what clinicians should analyze to determine which of their patients with heart failure and coronary disease to send to surgery, particularly in light of the benefits observed with CABG in the primary STICH analysis. Those data showed a 5% reduction in all-cause mortality at 6 years with the addition of CABG to medical therapy.

Dr. Bonow replied, "I think viability may be something you look at in some patients, but the point would be that there are other clinical variables, perhaps coronary anatomy, that one would bring into play."

Dr. Steven Bollings, with the Cardiovascular Center at the University of Michigan in Ann Arbor, said the primary STICH results provide a clear answer that patients with heart failure and left ventricular dysfunction benefit from coronary bypass surgery, but that the viability substudy raises a number of questions. He said that myocardial "may not be the No. 1 criterion by which we send patients to the operating room" and that other variables such as whether the patient has clear distal targets or is robust may be more important.

Dr. Gregg W. Stone of Columbia University, New York, said, "While I admit this is the clearly the best and most important viability study ever done, I don’t know that it definitively answers the question for us that viability doesn’t matter."

He pointed out that the viability data were based on only half of the STICH participants, the subsets were unbalanced with 80% of patients having viable myocardium and that some would say it’s not appropriate to look for interaction testing off of a negative end point.

"What I take away from this is that if there’s viability, I really want to be sure to revascularize," said Dr. Ted E. Feldman of NorthShore University HealthSystem in Evanston, Ill. "But prior to seeing these results, I was inclined to say if there wasn’t viability, not to vascularize. And the results of the trial challenge that historic bias," he added.

STICH Viability was supported by grants from the National Heart, Lung, and Blood Institute and Abbott Laboratories. Dr. Bonow had no relevant disclosures.

A program of regular tai chi exercises improved measures of quality of life in patients with chronic heart failure but failed to improve more conventional measures of exercise efficacy, compared with patients who only received education.

"Tai chi exercise, a multicomponent mind-body training modality that is safe and has good rates of adherence, may provide value in improving daily exercise, quality of life, self-efficacy, and mood in frail, deconditioned patients with systolic HF. A more restricted focus on traditional measured exercise capacity may underestimate the potential benefits of integrated interventions such as tai chi," wrote Dr. Gloria Y. Yeh and her coinvestigators in a study released April 25 in the Archives of Internal Medicine.

Photo credit: (c) Willie B. Thomas/iStockphoto.com

Tai chi is a gentle, meditative exercise of flowing circular movements, balance and weight shifting, breathing techniques, visualization, and focused internal awareness. "Tai chi may represent an additional exercise option for patients with HF because it integrates multiple relevant processes, including mild to moderate aerobic activity, upper and lower extremity training, and core strengthening," they said.

The researchers recruited 100 heart failure patients with a left ventricular ejection fraction of 40% or lower in the past 2 years, a stable medical regimen, and New York Heart Association class I-III from Boston medical practices.

They were randomly assigned to receive a 12-week tai chi exercise program or a heart health education program (attention control). All participants continued to receive usual care, noted Dr. Yeh, assistant professor of medicine at Beth Israel Deaconess and in the division for research and education in complementary and integrative medical therapies at Harvard Medical School, both in Boston, and her associates.

All assessments were performed at baseline and at 12 weeks. Patients performed a symptom-limited exercise test using a bicycle ramp protocol to determine peak oxygen uptake, a 6-minute walk test, and a Timed Up and Go functional assessment.

The researchers used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to assess disease-specific quality of life, the Profile of Mood States to assess emotional states expected to respond to clinical intervention, and the Cardiac Exercise Self-Efficacy Instrument to assess patient confidence in performing exercise-related activities.

The tai chi intervention consisted of 1-hour group classes held twice weekly for 12 weeks by certified instructors. Patients were encouraged to practice at home at least three times a week. Patients in the control group attended nurse practitioner–led education sessions twice weekly and were asked not to start tai chi during the study period.

The mean age of study participants was 67 years, the mean baseline LVEF was 29%, and the median NYHA class was II. Most patients were receiving beta-blockers (86%) and ACE inhibitors (85%).

At 12 weeks, significant improvements were seen in scores on the MLHFQ, Profile of Mood States (total mood disturbance, depression, and vigor subscales), and Cardiac Exercise Self-Efficacy Instrument in the tai chi group, compared with the heart health education group. There were no significant changes in serum biomarkers, which included B-type natriuretic peptide, catecholamines, and C-reactive protein, Dr. Yeh and her associates reported (Arch. Intern. Med. 2011;171:750-7).

Post hoc exploratory analyses pointed to subsets of patients who derived significant benefits from tai chi, compared with education only. Tai chi patients without implanted cardioverter defibrillators devices, those with NYHA class II and III symptoms, and those with a nonischemic etiology of HF improved significantly on the MLHFQ, compared with education-only patients. The researchers also found that participants with a higher baseline resting heart rate had greater improvements in the MLHFQ score in the tai chi group; there was no association in the control group.

"One of the purported mechanisms of mind-body exercises, such as tai chi, is favorable modulation of the autonomic nervous system. In our post hoc analyses, we found that, in participants with higher resting heart rates (and presumably more sympathetic nervous system ‘overdrive’), there was a greater benefit with tai chi," the investigators noted.

At the 6-month follow-up telephone contact, 34 patients in the tai chi group (68.0%) reported continued practice (including daily, weekly, and monthly). There were no adverse events related to the protocol.

Dr. Yeh and her associates reported no significant financial relationships.

A program of regular tai chi exercises improved measures of quality of life in patients with chronic heart failure but failed to improve more conventional measures of exercise efficacy, compared with patients who only received education.

"Tai chi exercise, a multicomponent mind-body training modality that is safe and has good rates of adherence, may provide value in improving daily exercise, quality of life, self-efficacy, and mood in frail, deconditioned patients with systolic HF. A more restricted focus on traditional measured exercise capacity may underestimate the potential benefits of integrated interventions such as tai chi," wrote Dr. Gloria Y. Yeh and her coinvestigators in a study released April 25 in the Archives of Internal Medicine.

Photo credit: (c) Willie B. Thomas/iStockphoto.com

Tai chi is a gentle, meditative exercise of flowing circular movements, balance and weight shifting, breathing techniques, visualization, and focused internal awareness. "Tai chi may represent an additional exercise option for patients with HF because it integrates multiple relevant processes, including mild to moderate aerobic activity, upper and lower extremity training, and core strengthening," they said.

The researchers recruited 100 heart failure patients with a left ventricular ejection fraction of 40% or lower in the past 2 years, a stable medical regimen, and New York Heart Association class I-III from Boston medical practices.

They were randomly assigned to receive a 12-week tai chi exercise program or a heart health education program (attention control). All participants continued to receive usual care, noted Dr. Yeh, assistant professor of medicine at Beth Israel Deaconess and in the division for research and education in complementary and integrative medical therapies at Harvard Medical School, both in Boston, and her associates.

All assessments were performed at baseline and at 12 weeks. Patients performed a symptom-limited exercise test using a bicycle ramp protocol to determine peak oxygen uptake, a 6-minute walk test, and a Timed Up and Go functional assessment.

The researchers used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to assess disease-specific quality of life, the Profile of Mood States to assess emotional states expected to respond to clinical intervention, and the Cardiac Exercise Self-Efficacy Instrument to assess patient confidence in performing exercise-related activities.

The tai chi intervention consisted of 1-hour group classes held twice weekly for 12 weeks by certified instructors. Patients were encouraged to practice at home at least three times a week. Patients in the control group attended nurse practitioner–led education sessions twice weekly and were asked not to start tai chi during the study period.

The mean age of study participants was 67 years, the mean baseline LVEF was 29%, and the median NYHA class was II. Most patients were receiving beta-blockers (86%) and ACE inhibitors (85%).

At 12 weeks, significant improvements were seen in scores on the MLHFQ, Profile of Mood States (total mood disturbance, depression, and vigor subscales), and Cardiac Exercise Self-Efficacy Instrument in the tai chi group, compared with the heart health education group. There were no significant changes in serum biomarkers, which included B-type natriuretic peptide, catecholamines, and C-reactive protein, Dr. Yeh and her associates reported (Arch. Intern. Med. 2011;171:750-7).

Post hoc exploratory analyses pointed to subsets of patients who derived significant benefits from tai chi, compared with education only. Tai chi patients without implanted cardioverter defibrillators devices, those with NYHA class II and III symptoms, and those with a nonischemic etiology of HF improved significantly on the MLHFQ, compared with education-only patients. The researchers also found that participants with a higher baseline resting heart rate had greater improvements in the MLHFQ score in the tai chi group; there was no association in the control group.

"One of the purported mechanisms of mind-body exercises, such as tai chi, is favorable modulation of the autonomic nervous system. In our post hoc analyses, we found that, in participants with higher resting heart rates (and presumably more sympathetic nervous system ‘overdrive’), there was a greater benefit with tai chi," the investigators noted.

At the 6-month follow-up telephone contact, 34 patients in the tai chi group (68.0%) reported continued practice (including daily, weekly, and monthly). There were no adverse events related to the protocol.

Dr. Yeh and her associates reported no significant financial relationships.

A program of regular tai chi exercises improved measures of quality of life in patients with chronic heart failure but failed to improve more conventional measures of exercise efficacy, compared with patients who only received education.

"Tai chi exercise, a multicomponent mind-body training modality that is safe and has good rates of adherence, may provide value in improving daily exercise, quality of life, self-efficacy, and mood in frail, deconditioned patients with systolic HF. A more restricted focus on traditional measured exercise capacity may underestimate the potential benefits of integrated interventions such as tai chi," wrote Dr. Gloria Y. Yeh and her coinvestigators in a study released April 25 in the Archives of Internal Medicine.

Photo credit: (c) Willie B. Thomas/iStockphoto.com

Tai chi is a gentle, meditative exercise of flowing circular movements, balance and weight shifting, breathing techniques, visualization, and focused internal awareness. "Tai chi may represent an additional exercise option for patients with HF because it integrates multiple relevant processes, including mild to moderate aerobic activity, upper and lower extremity training, and core strengthening," they said.

The researchers recruited 100 heart failure patients with a left ventricular ejection fraction of 40% or lower in the past 2 years, a stable medical regimen, and New York Heart Association class I-III from Boston medical practices.

They were randomly assigned to receive a 12-week tai chi exercise program or a heart health education program (attention control). All participants continued to receive usual care, noted Dr. Yeh, assistant professor of medicine at Beth Israel Deaconess and in the division for research and education in complementary and integrative medical therapies at Harvard Medical School, both in Boston, and her associates.

All assessments were performed at baseline and at 12 weeks. Patients performed a symptom-limited exercise test using a bicycle ramp protocol to determine peak oxygen uptake, a 6-minute walk test, and a Timed Up and Go functional assessment.

The researchers used the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to assess disease-specific quality of life, the Profile of Mood States to assess emotional states expected to respond to clinical intervention, and the Cardiac Exercise Self-Efficacy Instrument to assess patient confidence in performing exercise-related activities.

The tai chi intervention consisted of 1-hour group classes held twice weekly for 12 weeks by certified instructors. Patients were encouraged to practice at home at least three times a week. Patients in the control group attended nurse practitioner–led education sessions twice weekly and were asked not to start tai chi during the study period.

The mean age of study participants was 67 years, the mean baseline LVEF was 29%, and the median NYHA class was II. Most patients were receiving beta-blockers (86%) and ACE inhibitors (85%).

At 12 weeks, significant improvements were seen in scores on the MLHFQ, Profile of Mood States (total mood disturbance, depression, and vigor subscales), and Cardiac Exercise Self-Efficacy Instrument in the tai chi group, compared with the heart health education group. There were no significant changes in serum biomarkers, which included B-type natriuretic peptide, catecholamines, and C-reactive protein, Dr. Yeh and her associates reported (Arch. Intern. Med. 2011;171:750-7).

Post hoc exploratory analyses pointed to subsets of patients who derived significant benefits from tai chi, compared with education only. Tai chi patients without implanted cardioverter defibrillators devices, those with NYHA class II and III symptoms, and those with a nonischemic etiology of HF improved significantly on the MLHFQ, compared with education-only patients. The researchers also found that participants with a higher baseline resting heart rate had greater improvements in the MLHFQ score in the tai chi group; there was no association in the control group.

"One of the purported mechanisms of mind-body exercises, such as tai chi, is favorable modulation of the autonomic nervous system. In our post hoc analyses, we found that, in participants with higher resting heart rates (and presumably more sympathetic nervous system ‘overdrive’), there was a greater benefit with tai chi," the investigators noted.

At the 6-month follow-up telephone contact, 34 patients in the tai chi group (68.0%) reported continued practice (including daily, weekly, and monthly). There were no adverse events related to the protocol.

Dr. Yeh and her associates reported no significant financial relationships.

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

Nearly one-quarter of Medicare patients hospitalized for heart failure are subsequently discharged to a skilled nursing facility, and those patients are significantly more likely to be rehospitalized or die within 1 year than are similar patients discharged to home, according to the findings of a large observational study of more than 15,400 patients from 149 hospitals.

Absolute rehospitalization rates in those discharged to a skilled nursing facility vs. home were 27% vs. 23.5%, respectively, at 30 days, and 76.1% vs. 72.2%, respectively, at 1 year. All-cause mortality rates were 14.4% vs. 4.1% at 30 days and 53.5% vs. 29.1% at 1 year, Dr. Larry A. Allen and his colleagues reported online March 29 in Circulation: Heart Failure.

After adjustment for numerous demographic and health-related factors, discharge to a skilled nursing facility in these patients remained significantly associated with an increased risk of death (hazard ratio 1.76), said Dr. Allen of the Colorado Cardiovascular Outcomes Research Consortium, University of Colorado Denver, Aurora, Colo. (Circulation: Heart Failure 2011 March 29 [doi:10.1161/CIRCHEARTFAILURE.110.959171]).

Patients included in the analysis were 15,459 adults aged 65 years or older (median age 80 years) who were discharged to a skilled nursing facility (24.1%), to home with home health service (22.3%), or to home with self-care (53.6%). The patients had been hospitalized for heart failure for at least 3 days (median 5 days) during 2005-2006.

The patients were part of the Get With The Guidelines – Heart Failure Program registry, an ongoing, voluntary quality-improvement initiative of the American Heart Association, the investigators said.

Factors found to be significantly associated with discharge to a skilled nursing facility included longer hospital stay (odds ratio 1.12 per day); advanced age (OR 1.98 per 10-year increase); female sex (OR 1.53); systolic blood pressure (OR 0.94 per 10 mm Hg increase); left ventricular ejection fraction less than 40% (OR 0.91); sodium level (OR 1.05 per 10 mEq/L increase); and history of hyperlipidemia (OR 0.74), anemia (OR 1.31), diabetes (OR 1.19), valvular heart disease (OR 0.72), myocardial infarction (OR 0.86), bypass surgery or percutaneous coronary intervention (OR 0.80), implantable defibrillator (OR 0.76), depression (OR 2.11), stroke (OR 1.55), peripheral vascular disease (OR 1.13), or chronic obstructive pulmonary disease or asthma (OR 1.11).

Across the country, the rate of discharges to skilled nursing facilities was highest in the Northeast (30%) and lowest in the West (23.6%). Hospitals that treated more racial minorities and younger patients were among those with the lowest rates of discharge to skilled nursing facilities.

In this study, hospitalized heart failure patients who were discharged to a skilled nursing facility were 79% more likely to die than those discharged to home – even after adjusting for a wide range of patient factors known to be associated with adverse outcomes, the investigators said.

"However, discharge to [a skilled nursing facility] is by its very nature determined by criteria such as poor mobility, cognitive impairment, frailty, and poor in-home support, which are also important determinants of outcome," they wrote, noting that those determinants of outcome were not captured in this analysis. Therefore, the researchers said, conclusions about whether discharge to a skilled nursing facility directly impacts patient outcomes cannot be drawn.

Still, the findings have potential implications for communicating prognoses to patients and families, medical decision-making, and assessing care provided at skilled nursing facilities, they said.

The high absolute rates of death following discharge to skilled nursing facilities, in particular, have potential implications for communication, discharge planning, and goals of care, they said.

"Additionally, we must consider whether a different set of quality measures [is] needed for this unique group of patients," the investigators concluded.

This study was funded by the American Heart Association, GlaxoSmithKline, and Medtronic through their support of the Get With The Guidelines – Heart Failure Program, and the Agency for Healthcare Research and Quality. Dr. Allen had no conflicts of interest to disclose. Other authors on the study reported numerous relationships with various pharmaceutical companies and other organizations.

NEW ORLEANS – Using speckle tracking echocardiography to guide pacemaker lead placement improved the outcomes of cardiac resynchronization therapy for patients with severe heart failure in TARGET, said to be the first randomized clinical trial to study the feasibility and outcomes of a targeted approach to left ventricular lead placement.

When speckle-tracking echocardiography (STE) was used to identify target sites for pacemaker lead placement for individual patients, leads were more likely to be placed at concordant sites. The result was improved echocardiographic response at 6 months – defined as a greater than 15% change in left ventricular end systolic volume (LVESV) from baseline to 6-month follow-up. The STE group had a 70% response as compared with a 55% response in the group with conventional lead placement without echocardiography guidance (P = .031), reported Dr. Fakhar Z. Khan, of Cambridge (U.K.) University, who reported the results of TARGET on April 5 at the annual meeting of the American College of Cardiology.

Lower rates were also seen with STE for the combined end point of all-cause mortality and heart failure hospitalization. The difference was primarily driven by fewer heart failure hospitalizations. Looking at mortality alone at a mean follow-up of 400 days, the two groups did not significantly differ.

"This is a well-designed, well-conducted study with impressive differences in clinical outcomes," said Dr. Byron Kwock Lee, who is with the University of California, San Francisco, and chaired the session where the TARGET results were presented. "Other studies have shown echocardiographic outcomes but have had difficulty showing clinical differences."

"I am impressed that the modest echocardiographic changes translated to dramatic clinical effects," commented Dr. Michael Crawford, also of the University of California, San Francisco, and a panelist at the presentation of the study results.

Up to 40% of patients fail to gain significant clinical benefit from cardiac resynchronization therapy, Dr. Khan noted. The position of the left ventricular lead has emerged as an important determinant of response, with better results achieved when pacing at the latest site of contraction and lesser responses noted when pacing areas of scar.

Speckle tracking radial strain imaging correlates with delayed enhanced cardiac MRI for determination of scar, Dr. Khan said. In patients undergoing cardiac resynchronization therapy, less than 10% amplitude of radial strain at the left ventricular pacing site has a high negative predictive value (91%) for response.

Using STE, "we found that concordant lead placement, baseline dyssynchrony, and pacing away from areas of scar are strongly related to improved outcomes," he said.

The single blinded, randomized, controlled trial enrolled 220 patients recruited from three different hospitals in the U.K. Participants were in sinus rhythm, had severe heart failure (NYHA Class III/IV), left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 msec. Patients were randomized in a 1:1 ratio to receive either standard lead placement without the benefit of echocardiographic guidance or targeted lead placement using STE to position the lead at the latest site of contraction and away from areas of scar. Following implantation, all devices were optimized using echocardiography.

Concordant lead placement was achieved in 61% of the STE group vs. 45% of control group. Placement was adjacent in 25% of the STE group and 28% of the control group, and was remote in 10% and 24%, respectively.

At baseline, both groups were comparable in demographic and disease characteristics. Mean age was about 70 years, about 86% were male, about 94% had NYHA Class III heart failure, and 56% had underlying ischemic cardiomyopathy.

Both groups had a 14% rate of implant-related complications. Procedural length of time was similar for both groups.

In addition to the primary end point improvements in echocardiographic response at 6-month follow-up, the STE group also had significantly improved clinical end points, compared with the standard placement group. Statistically significant differences from baseline to follow-up for the STE group vs. the standard placement group included improvement in heart failure class (P = .002), 6-mile walk test results (P = .01), and quality-of-life scores. (P = .02).

Patients in the study will continue to have ongoing follow-up.

"STE software can be applied to any existing echocardiographic image at no additional risk to the patient," Dr. Khan said. "STE makes targeting of the lead feasible at any facility that performs echocardiography and has the software available to analyze their images, so it is widely accessible at smaller centers and nonacademic hospitals where more and more pacemakers are being implanted. That being said, it requires training and experience."

Dr. Khan had no relevant financial disclosures.

NEW ORLEANS – Using speckle tracking echocardiography to guide pacemaker lead placement improved the outcomes of cardiac resynchronization therapy for patients with severe heart failure in TARGET, said to be the first randomized clinical trial to study the feasibility and outcomes of a targeted approach to left ventricular lead placement.

When speckle-tracking echocardiography (STE) was used to identify target sites for pacemaker lead placement for individual patients, leads were more likely to be placed at concordant sites. The result was improved echocardiographic response at 6 months – defined as a greater than 15% change in left ventricular end systolic volume (LVESV) from baseline to 6-month follow-up. The STE group had a 70% response as compared with a 55% response in the group with conventional lead placement without echocardiography guidance (P = .031), reported Dr. Fakhar Z. Khan, of Cambridge (U.K.) University, who reported the results of TARGET on April 5 at the annual meeting of the American College of Cardiology.

Lower rates were also seen with STE for the combined end point of all-cause mortality and heart failure hospitalization. The difference was primarily driven by fewer heart failure hospitalizations. Looking at mortality alone at a mean follow-up of 400 days, the two groups did not significantly differ.

"This is a well-designed, well-conducted study with impressive differences in clinical outcomes," said Dr. Byron Kwock Lee, who is with the University of California, San Francisco, and chaired the session where the TARGET results were presented. "Other studies have shown echocardiographic outcomes but have had difficulty showing clinical differences."

"I am impressed that the modest echocardiographic changes translated to dramatic clinical effects," commented Dr. Michael Crawford, also of the University of California, San Francisco, and a panelist at the presentation of the study results.

Up to 40% of patients fail to gain significant clinical benefit from cardiac resynchronization therapy, Dr. Khan noted. The position of the left ventricular lead has emerged as an important determinant of response, with better results achieved when pacing at the latest site of contraction and lesser responses noted when pacing areas of scar.

Speckle tracking radial strain imaging correlates with delayed enhanced cardiac MRI for determination of scar, Dr. Khan said. In patients undergoing cardiac resynchronization therapy, less than 10% amplitude of radial strain at the left ventricular pacing site has a high negative predictive value (91%) for response.

Using STE, "we found that concordant lead placement, baseline dyssynchrony, and pacing away from areas of scar are strongly related to improved outcomes," he said.

The single blinded, randomized, controlled trial enrolled 220 patients recruited from three different hospitals in the U.K. Participants were in sinus rhythm, had severe heart failure (NYHA Class III/IV), left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 msec. Patients were randomized in a 1:1 ratio to receive either standard lead placement without the benefit of echocardiographic guidance or targeted lead placement using STE to position the lead at the latest site of contraction and away from areas of scar. Following implantation, all devices were optimized using echocardiography.

Concordant lead placement was achieved in 61% of the STE group vs. 45% of control group. Placement was adjacent in 25% of the STE group and 28% of the control group, and was remote in 10% and 24%, respectively.

At baseline, both groups were comparable in demographic and disease characteristics. Mean age was about 70 years, about 86% were male, about 94% had NYHA Class III heart failure, and 56% had underlying ischemic cardiomyopathy.

Both groups had a 14% rate of implant-related complications. Procedural length of time was similar for both groups.

In addition to the primary end point improvements in echocardiographic response at 6-month follow-up, the STE group also had significantly improved clinical end points, compared with the standard placement group. Statistically significant differences from baseline to follow-up for the STE group vs. the standard placement group included improvement in heart failure class (P = .002), 6-mile walk test results (P = .01), and quality-of-life scores. (P = .02).

Patients in the study will continue to have ongoing follow-up.

"STE software can be applied to any existing echocardiographic image at no additional risk to the patient," Dr. Khan said. "STE makes targeting of the lead feasible at any facility that performs echocardiography and has the software available to analyze their images, so it is widely accessible at smaller centers and nonacademic hospitals where more and more pacemakers are being implanted. That being said, it requires training and experience."

Dr. Khan had no relevant financial disclosures.

NEW ORLEANS – Using speckle tracking echocardiography to guide pacemaker lead placement improved the outcomes of cardiac resynchronization therapy for patients with severe heart failure in TARGET, said to be the first randomized clinical trial to study the feasibility and outcomes of a targeted approach to left ventricular lead placement.

When speckle-tracking echocardiography (STE) was used to identify target sites for pacemaker lead placement for individual patients, leads were more likely to be placed at concordant sites. The result was improved echocardiographic response at 6 months – defined as a greater than 15% change in left ventricular end systolic volume (LVESV) from baseline to 6-month follow-up. The STE group had a 70% response as compared with a 55% response in the group with conventional lead placement without echocardiography guidance (P = .031), reported Dr. Fakhar Z. Khan, of Cambridge (U.K.) University, who reported the results of TARGET on April 5 at the annual meeting of the American College of Cardiology.

Lower rates were also seen with STE for the combined end point of all-cause mortality and heart failure hospitalization. The difference was primarily driven by fewer heart failure hospitalizations. Looking at mortality alone at a mean follow-up of 400 days, the two groups did not significantly differ.

"This is a well-designed, well-conducted study with impressive differences in clinical outcomes," said Dr. Byron Kwock Lee, who is with the University of California, San Francisco, and chaired the session where the TARGET results were presented. "Other studies have shown echocardiographic outcomes but have had difficulty showing clinical differences."

"I am impressed that the modest echocardiographic changes translated to dramatic clinical effects," commented Dr. Michael Crawford, also of the University of California, San Francisco, and a panelist at the presentation of the study results.

Up to 40% of patients fail to gain significant clinical benefit from cardiac resynchronization therapy, Dr. Khan noted. The position of the left ventricular lead has emerged as an important determinant of response, with better results achieved when pacing at the latest site of contraction and lesser responses noted when pacing areas of scar.

Speckle tracking radial strain imaging correlates with delayed enhanced cardiac MRI for determination of scar, Dr. Khan said. In patients undergoing cardiac resynchronization therapy, less than 10% amplitude of radial strain at the left ventricular pacing site has a high negative predictive value (91%) for response.

Using STE, "we found that concordant lead placement, baseline dyssynchrony, and pacing away from areas of scar are strongly related to improved outcomes," he said.

The single blinded, randomized, controlled trial enrolled 220 patients recruited from three different hospitals in the U.K. Participants were in sinus rhythm, had severe heart failure (NYHA Class III/IV), left ventricular ejection fractions less than 35%, and QRS intervals greater than 120 msec. Patients were randomized in a 1:1 ratio to receive either standard lead placement without the benefit of echocardiographic guidance or targeted lead placement using STE to position the lead at the latest site of contraction and away from areas of scar. Following implantation, all devices were optimized using echocardiography.

Concordant lead placement was achieved in 61% of the STE group vs. 45% of control group. Placement was adjacent in 25% of the STE group and 28% of the control group, and was remote in 10% and 24%, respectively.

At baseline, both groups were comparable in demographic and disease characteristics. Mean age was about 70 years, about 86% were male, about 94% had NYHA Class III heart failure, and 56% had underlying ischemic cardiomyopathy.

Both groups had a 14% rate of implant-related complications. Procedural length of time was similar for both groups.

In addition to the primary end point improvements in echocardiographic response at 6-month follow-up, the STE group also had significantly improved clinical end points, compared with the standard placement group. Statistically significant differences from baseline to follow-up for the STE group vs. the standard placement group included improvement in heart failure class (P = .002), 6-mile walk test results (P = .01), and quality-of-life scores. (P = .02).

Patients in the study will continue to have ongoing follow-up.

"STE software can be applied to any existing echocardiographic image at no additional risk to the patient," Dr. Khan said. "STE makes targeting of the lead feasible at any facility that performs echocardiography and has the software available to analyze their images, so it is widely accessible at smaller centers and nonacademic hospitals where more and more pacemakers are being implanted. That being said, it requires training and experience."

Dr. Khan had no relevant financial disclosures.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

NEW ORLEANS – The addition of coronary bypass surgery to aggressive medical care failed to reduce the primary end point of all-cause death in patients with coronary artery disease and heart failure in the Surgical Treatment for Ischemic Heart Failure trial.

Still, several experts characterized the trial as a success and its lead author, Dr. Eric Velazquez, said the data support coronary artery disease (CAD) assessment in all patients presenting with heart failure.

After 6 years of follow-up among 1,202 randomized patients, there was a nonsignificant reduction in Kaplan Meier all-cause mortality rates with coronary artery bypass grafting (CABG) plus medical therapy, from 46% to 41%, Dr. Velazquez reported on April 4 at the annual meeting of the American College of Cardiology.

After adjusting this outcome for prespecified baseline variables, the hazard ratio was 0.82 and P value .039.

Crude all-cause mortality rates fell, albeit not significantly, from 41% to 36%, as simultaneously reported online (N. Engl. J. Med. 2011 [10.1056/NEJMa1100356]).

Among key secondary outcomes, however, bypass surgery significantly reduced Kaplan-Meier cardiovascular mortality event rates, from 39% to 32%, and crude cardiovascular mortality rates, from 33% to 28%.

Both Kaplan-Meier event rates and crude rates of death or cardiovascular hospitalization were significantly reduced with bypass, from 68% to 58%. The secondary outcomes remained significant after adjustment.

As anticipated, CABG was associated with an early risk of death that took 2 years to abate, observed Dr. Velazquez, director of the cardiac diagnostic unit and echocardiography laboratories at Duke University Medical Center in Durham, N.C.

"Decision making for CABG is complex," he said. "It should be individualized and now with the results of the STICH trial, patients should be informed of the short-term risk for a potential long-term benefit."

In all, 17% of the 602 patients randomly assigned to medical therapy alone crossed over to receive bypass surgery before the end of follow-up, and 9% of the 610 patients assigned to CABG received medical treatment only.

When the data were analyzed on an as-treated basis from the resulting 592 medical therapy and 620 CABG patients, the addition of bypass surgery significantly reduced deaths from any cause by 11%, from 49% to 38% (P value less than .001; HR, 0.70), Dr. Velazquez said.

The researchers then performed a per-protocol analysis of the 537 medical therapy patients who did not cross over to CABG during the first year of follow-up and the 555 CABG patients who actually underwent the procedure. Once again, the primary outcome of all-cause mortality was significantly reduced 11%, this time from 48% to 37% (P = .005, HR 0.76).

Current guidelines don’t support evaluation of coronary artery disease in patients with heart failure who present without chest pain, resulting in a lost opportunity for clinicians and leaving the exact number of patients for whom the results of STICH would apply unclear, Dr. Velazquez said in an interview.

"I think the guidelines need to recognize that coronary artery disease presents in many ways in our patients and that evaluation of coronary artery disease is important not only for consideration of bypass surgery, but also to optimize medical therapy and CAD medication," he said.

Despite the medical adherence and operative results achieved in the trial, STICH-like patients remain at substantial risk with a 5-year mortality rate of 40% with medication only.

Invited discussant Dr. Bernard Gersch said "We have known for decades that, in patients with left-ventricular dysfunction and ischemia, left-ventricular dysfunction is the major cause of mortality. And you have now proven the concept. This is an incredible trial. It’s a stunning achievement and very difficult to do."

Future analyses of the mechanisms of benefit associated with bypass surgery will prove important in determining whether the benefit is from an improvement in diastolic dysfunction or perhaps a reduction in sudden cardiac death or recurrent infarction, added Dr. Gersch, professor of medicine at the Mayo Clinic, Rochester, Minn.

Fellow discussant Dr. Steven Bolling said he agreed that STICH is a landmark trial and called the difference in outcomes between the intention-to-treat and actual treatment analyses "interesting."

Yet, "if the biological effect that our patients feel is really what treatment they receive, then under that analysis, of course, as a surgeon, you must conclude that patients with left-ventricular dysfunction should receive coronary artery bypass," added professor of surgery and director of the mitral valve clinic at the University of Michigan, Ann Arbor.

Patients in STICH were randomized at 99 medical centers in 22 countries and had a left ventricular ejection fraction of 35% or less and coronary artery disease suitable for CABG. The median time to CABG was 10 days. In all, 91% of patients received at least one arterial conduit, 86% received at least one venous conduit, and 88% received a total of at least two grafts. The median hospital stay was 9 days (range 7-13).

Only 5 of the 1,202 patients were not evaluable with a median follow-up of 40 months. The overall duration of follow-up was 56 months.

The STICH Extension study will test the durability of the current results at 10 years.

STICH was supported by grants from the National Heart, Lung, and Blood Institute (90%) and Abbott Laboratories (2%). Dr. Velazquez reported receiving consulting fees from Novartis, Gilead, and Boehringer-Ingelheim Pharmaceuticals. Two of his coauthors reported similar relationships with Medtronic, St. Jude Medical, Biotronik, CardioMEMS, and Novartis.

Dr. Gersch has financial relationships with several device and pharmaceutical companies, including Boston Scientific, Merck, Ortho-McNeil, and Abbott Laboratories. Dr. Bolling has received remuneration from Edwards Lifesciences.

CHICAGO – Exposing patients with heart failure to altitude training using a portable simulated altitude device appears to provide clinical benefits.

The 10 patients with systolic heart failure enrolled to date in a pilot study responded to a maximum simulated altitude of 2,700 m with significant improvements in left ventricular ejection fraction, quality of life, and three different measures of exercise performance, Dr. Philip Formica reported at the meeting.

Importantly, these benefits were sustained for at least 4 weeks after completion of the simulated altitude treatment sessions using the Hypoxico Inc. altitude tent, added Dr. Formica of Albert Einstein College of Medicine and Montefiore Medical Center, New York.

Commercially available high-altitude simulators such as this are popular with elite bicycle racers, distance runners, and other endurance athletes because adaptation to altitude results in physiologic changes that enhance oxygen delivery to the periphery. Athletes use the devices at home in order to, as their coaches preach, “sleep high and train low.”

The hypothesis tested in this study was that patients with heart failure would also benefit from acclimatization to altitude. The physiologic changes accompanying this acclimatization include an erythropoietin-induced increase in RBC mass, a rightward shift of the oxyhemoglobulin dissociation curve, improved oxygen transport stemming from increased tidal volume and hypoxic ventilatory response, improved left ventricular end-systolic diameter and stroke volume, and greater skeletal muscle capillary density.

The treatment protocol consisted of 10 sessions with the patient sitting in the normobaric hypoxic enclosure; the sessions, each lasting 3–4 hours, were spread over the course of 22 days and were done on an alternate-day schedule. Forty-eight hours prior to the first session, patients went on twice-daily 125-mg oral acetazolamide, a drug long used to prevent headache and other altitude sickness symptoms. Patients started at a simulated altitude of 1,500 m, increasing by 300 m per session to a maximum elevation of 2,700 m.

The altitude simulation device draws in ambient air, separates the oxygen from the nitrogen, and then pumps high-flow hypoxic air into a semisealed enclosure. Altitudes of up to 6,500 m can be simulated.

The patients had a mean 83-month duration of heart failure. All of them tolerated the treatment sessions without any adverse effects. A mean 91% oxygen saturation was maintained at maximum simulated altitude. Nine of 10 patients showed significant improvement in all three measures of exercise performance (see table).

These results are promising, but need to be confirmed in a larger number of heart failure patients, said Dr. Formica, who had no relevant financial disclosures.

Source Elsevier Global Medical News

CHICAGO – Exposing patients with heart failure to altitude training using a portable simulated altitude device appears to provide clinical benefits.

The 10 patients with systolic heart failure enrolled to date in a pilot study responded to a maximum simulated altitude of 2,700 m with significant improvements in left ventricular ejection fraction, quality of life, and three different measures of exercise performance, Dr. Philip Formica reported at the meeting.

Importantly, these benefits were sustained for at least 4 weeks after completion of the simulated altitude treatment sessions using the Hypoxico Inc. altitude tent, added Dr. Formica of Albert Einstein College of Medicine and Montefiore Medical Center, New York.

Commercially available high-altitude simulators such as this are popular with elite bicycle racers, distance runners, and other endurance athletes because adaptation to altitude results in physiologic changes that enhance oxygen delivery to the periphery. Athletes use the devices at home in order to, as their coaches preach, “sleep high and train low.”

The hypothesis tested in this study was that patients with heart failure would also benefit from acclimatization to altitude. The physiologic changes accompanying this acclimatization include an erythropoietin-induced increase in RBC mass, a rightward shift of the oxyhemoglobulin dissociation curve, improved oxygen transport stemming from increased tidal volume and hypoxic ventilatory response, improved left ventricular end-systolic diameter and stroke volume, and greater skeletal muscle capillary density.

The treatment protocol consisted of 10 sessions with the patient sitting in the normobaric hypoxic enclosure; the sessions, each lasting 3–4 hours, were spread over the course of 22 days and were done on an alternate-day schedule. Forty-eight hours prior to the first session, patients went on twice-daily 125-mg oral acetazolamide, a drug long used to prevent headache and other altitude sickness symptoms. Patients started at a simulated altitude of 1,500 m, increasing by 300 m per session to a maximum elevation of 2,700 m.

The altitude simulation device draws in ambient air, separates the oxygen from the nitrogen, and then pumps high-flow hypoxic air into a semisealed enclosure. Altitudes of up to 6,500 m can be simulated.

The patients had a mean 83-month duration of heart failure. All of them tolerated the treatment sessions without any adverse effects. A mean 91% oxygen saturation was maintained at maximum simulated altitude. Nine of 10 patients showed significant improvement in all three measures of exercise performance (see table).

These results are promising, but need to be confirmed in a larger number of heart failure patients, said Dr. Formica, who had no relevant financial disclosures.

Source Elsevier Global Medical News

CHICAGO – Exposing patients with heart failure to altitude training using a portable simulated altitude device appears to provide clinical benefits.

The 10 patients with systolic heart failure enrolled to date in a pilot study responded to a maximum simulated altitude of 2,700 m with significant improvements in left ventricular ejection fraction, quality of life, and three different measures of exercise performance, Dr. Philip Formica reported at the meeting.

Importantly, these benefits were sustained for at least 4 weeks after completion of the simulated altitude treatment sessions using the Hypoxico Inc. altitude tent, added Dr. Formica of Albert Einstein College of Medicine and Montefiore Medical Center, New York.

Commercially available high-altitude simulators such as this are popular with elite bicycle racers, distance runners, and other endurance athletes because adaptation to altitude results in physiologic changes that enhance oxygen delivery to the periphery. Athletes use the devices at home in order to, as their coaches preach, “sleep high and train low.”

The hypothesis tested in this study was that patients with heart failure would also benefit from acclimatization to altitude. The physiologic changes accompanying this acclimatization include an erythropoietin-induced increase in RBC mass, a rightward shift of the oxyhemoglobulin dissociation curve, improved oxygen transport stemming from increased tidal volume and hypoxic ventilatory response, improved left ventricular end-systolic diameter and stroke volume, and greater skeletal muscle capillary density.

The treatment protocol consisted of 10 sessions with the patient sitting in the normobaric hypoxic enclosure; the sessions, each lasting 3–4 hours, were spread over the course of 22 days and were done on an alternate-day schedule. Forty-eight hours prior to the first session, patients went on twice-daily 125-mg oral acetazolamide, a drug long used to prevent headache and other altitude sickness symptoms. Patients started at a simulated altitude of 1,500 m, increasing by 300 m per session to a maximum elevation of 2,700 m.

The altitude simulation device draws in ambient air, separates the oxygen from the nitrogen, and then pumps high-flow hypoxic air into a semisealed enclosure. Altitudes of up to 6,500 m can be simulated.

The patients had a mean 83-month duration of heart failure. All of them tolerated the treatment sessions without any adverse effects. A mean 91% oxygen saturation was maintained at maximum simulated altitude. Nine of 10 patients showed significant improvement in all three measures of exercise performance (see table).

These results are promising, but need to be confirmed in a larger number of heart failure patients, said Dr. Formica, who had no relevant financial disclosures.

Source Elsevier Global Medical News

Left ventricular unloading in patients with end-stage heart failure has been shown to improve with the use of a left-ventricular assist device, according to the results of several recent clinical studies. This improvement includes favorable changes in myocardial structure and function, including beta-adrenergic responsiveness and myocyte contractility.

Several molecular and genetic mechanisms have been correlated with these changes and might provide the basis for improvements in device behavior, as well as indications for potential targets for new therapeutic drugs and altered regimens for existing drugs.

Such new treatments may have the potential to benefit not only patients who have received LVADs, but also heart failure patients as a whole, as reported in a state-of-the-art article (J. Am. Coll. Cardiol. 2011;57:641-52).

The LVAD population presents a unique and valuable opportunity to obtain myocardial tissue of patients with end-stage heart failure (HF) at the time of implantation, and often at the time of heart and/or LVAD explantation, after a period of unloading, according to Jennifer L. Hall, Ph.D., of the University of Minnesota, Minneapolis, and her colleagues in the United States and Europe. These tissue samples allow paired comparisons of before and after changes in molecular, genetic, and cytologic markers indicative of improvements that occur with the reverse remodeling of the human heart seen in response to LVADs.

The researchers supported their conclusions with a review of recent clinical trials and assembled data from a report by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) covering the years 2006–2009, which included the introduction of continuous-flow technology as well as the original pulsatile flow devices.

Mechanical improvements in failing hearts treated with LVADS have been characterized by partial recovery of the contractile performance of myocytes. This includes improvements of the magnitude of shortening in isolated myocytes in response to beta-adrenergic agonists, of basal relaxation, and in the rise and fall in tension in trabecular muscle preparations.

Relevant markers and pathways found to be improved or normalized by LVAD support included:

Beta-adrenergic signalling. Improvements in developed tension with LVADs have been shown to be associated with an increased beta-adrenergic receptor density. Because a novel combination of LVAD support and pharmacologic therapy – including the selective beta-2 agonist clenbuterol – showed promise in restoring ventricular function in patients with heart failure, investigators analyzed six paired human heart samples isolated at the time of LVAD implantation and at the time of LVAD explantation due to sufficient myocardial recovery. Significant changes to a number of genes in the beta-adrenergic signaling pathway occurred in recovering hearts.

Calcium handling. Although improvements in basal relaxation rates with LVADs have not been definitively linked to changes in calcium handling, the largest improvements in action potential and sarcoplasmic reticulum calcium content occurred in patients who achieved clinical recovery in response to LVADs and pharmacological therapy. However, improvements in calcium handling and contractility appear time dependent, with patients with shorter durations of support (less than 115 days) showing improvement, which reverted back to failing levels in patients with longer durations of support.

Metabolism and growth factor–related genes. Several genes that regulated metabolism were found to change their expression during LVAD-supported recovery. These included arginine:glycine amidinotransferase (AGAT), a rate-limiting enzyme in the creatine synthesis pathway, which was significantly down-regulated after unloading in the recovered hearts, returning to normal levels, in direct contrast to the up-regulation of AGAT seen in patients with heart failure. Insulin growth factor was elevated in patients at the time of LVAD explantation due to recovery. This was thought to aid in limiting atrophy and apoptosis during reverse remodeling and to promote repair and regeneration.

Natriuretic peptides and chromogranin A. Unloading a failing heart with an LVAD was associated with a decrease in natriuretic peptides (which are activated during heart failure) and reestablishment of the local responsiveness of a key enzyme, chromogranin A, to cardiac atrial natriuretic peptide.

But all is not perfect in the LVAD-supported heart. In one study, there was a significant increase in total and cross-linked collagen in the myocardium, compared with nonfailing and medically managed patients with heart failure, which correlated with increased left ventricular stiffness. “Interestingly, the majority of [these] LVAD patients after implantation were not on ACE inhibitors, which have been demonstrated to improve fibrosis and remodeling,” the authors wrote.

A subsequent retrospective cohort study of the same group, comparing LVAD patients who did and did not receive ACE inhibitor therapy after implantation, showed a significant decrease in collagen content and myocardial stiffness in the cohort with LVADs and ACE inhibitors. “These findings support the hypothesis that maximizing optimal medical management after ventricular unloading with LVADs may promote myocardial recovery.”

The study was sponsored by the National Institutes of Health, the American Heart Association, and the National Institutes for Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London. Several of the authors reported receiving research support and/or honoraria or speakers fees from Thoratec, Heartware Inc., and Medtronic, all manufacturers of LVADs.

Left ventricular unloading in patients with end-stage heart failure has been shown to improve with the use of a left-ventricular assist device, according to the results of several recent clinical studies. This improvement includes favorable changes in myocardial structure and function, including beta-adrenergic responsiveness and myocyte contractility.

Several molecular and genetic mechanisms have been correlated with these changes and might provide the basis for improvements in device behavior, as well as indications for potential targets for new therapeutic drugs and altered regimens for existing drugs.

Such new treatments may have the potential to benefit not only patients who have received LVADs, but also heart failure patients as a whole, as reported in a state-of-the-art article (J. Am. Coll. Cardiol. 2011;57:641-52).

The LVAD population presents a unique and valuable opportunity to obtain myocardial tissue of patients with end-stage heart failure (HF) at the time of implantation, and often at the time of heart and/or LVAD explantation, after a period of unloading, according to Jennifer L. Hall, Ph.D., of the University of Minnesota, Minneapolis, and her colleagues in the United States and Europe. These tissue samples allow paired comparisons of before and after changes in molecular, genetic, and cytologic markers indicative of improvements that occur with the reverse remodeling of the human heart seen in response to LVADs.

The researchers supported their conclusions with a review of recent clinical trials and assembled data from a report by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) covering the years 2006–2009, which included the introduction of continuous-flow technology as well as the original pulsatile flow devices.

Mechanical improvements in failing hearts treated with LVADS have been characterized by partial recovery of the contractile performance of myocytes. This includes improvements of the magnitude of shortening in isolated myocytes in response to beta-adrenergic agonists, of basal relaxation, and in the rise and fall in tension in trabecular muscle preparations.

Relevant markers and pathways found to be improved or normalized by LVAD support included:

Beta-adrenergic signalling. Improvements in developed tension with LVADs have been shown to be associated with an increased beta-adrenergic receptor density. Because a novel combination of LVAD support and pharmacologic therapy – including the selective beta-2 agonist clenbuterol – showed promise in restoring ventricular function in patients with heart failure, investigators analyzed six paired human heart samples isolated at the time of LVAD implantation and at the time of LVAD explantation due to sufficient myocardial recovery. Significant changes to a number of genes in the beta-adrenergic signaling pathway occurred in recovering hearts.

Calcium handling. Although improvements in basal relaxation rates with LVADs have not been definitively linked to changes in calcium handling, the largest improvements in action potential and sarcoplasmic reticulum calcium content occurred in patients who achieved clinical recovery in response to LVADs and pharmacological therapy. However, improvements in calcium handling and contractility appear time dependent, with patients with shorter durations of support (less than 115 days) showing improvement, which reverted back to failing levels in patients with longer durations of support.

Metabolism and growth factor–related genes. Several genes that regulated metabolism were found to change their expression during LVAD-supported recovery. These included arginine:glycine amidinotransferase (AGAT), a rate-limiting enzyme in the creatine synthesis pathway, which was significantly down-regulated after unloading in the recovered hearts, returning to normal levels, in direct contrast to the up-regulation of AGAT seen in patients with heart failure. Insulin growth factor was elevated in patients at the time of LVAD explantation due to recovery. This was thought to aid in limiting atrophy and apoptosis during reverse remodeling and to promote repair and regeneration.

Natriuretic peptides and chromogranin A. Unloading a failing heart with an LVAD was associated with a decrease in natriuretic peptides (which are activated during heart failure) and reestablishment of the local responsiveness of a key enzyme, chromogranin A, to cardiac atrial natriuretic peptide.

But all is not perfect in the LVAD-supported heart. In one study, there was a significant increase in total and cross-linked collagen in the myocardium, compared with nonfailing and medically managed patients with heart failure, which correlated with increased left ventricular stiffness. “Interestingly, the majority of [these] LVAD patients after implantation were not on ACE inhibitors, which have been demonstrated to improve fibrosis and remodeling,” the authors wrote.

A subsequent retrospective cohort study of the same group, comparing LVAD patients who did and did not receive ACE inhibitor therapy after implantation, showed a significant decrease in collagen content and myocardial stiffness in the cohort with LVADs and ACE inhibitors. “These findings support the hypothesis that maximizing optimal medical management after ventricular unloading with LVADs may promote myocardial recovery.”

The study was sponsored by the National Institutes of Health, the American Heart Association, and the National Institutes for Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London. Several of the authors reported receiving research support and/or honoraria or speakers fees from Thoratec, Heartware Inc., and Medtronic, all manufacturers of LVADs.

Left ventricular unloading in patients with end-stage heart failure has been shown to improve with the use of a left-ventricular assist device, according to the results of several recent clinical studies. This improvement includes favorable changes in myocardial structure and function, including beta-adrenergic responsiveness and myocyte contractility.

Several molecular and genetic mechanisms have been correlated with these changes and might provide the basis for improvements in device behavior, as well as indications for potential targets for new therapeutic drugs and altered regimens for existing drugs.

Such new treatments may have the potential to benefit not only patients who have received LVADs, but also heart failure patients as a whole, as reported in a state-of-the-art article (J. Am. Coll. Cardiol. 2011;57:641-52).

The LVAD population presents a unique and valuable opportunity to obtain myocardial tissue of patients with end-stage heart failure (HF) at the time of implantation, and often at the time of heart and/or LVAD explantation, after a period of unloading, according to Jennifer L. Hall, Ph.D., of the University of Minnesota, Minneapolis, and her colleagues in the United States and Europe. These tissue samples allow paired comparisons of before and after changes in molecular, genetic, and cytologic markers indicative of improvements that occur with the reverse remodeling of the human heart seen in response to LVADs.

The researchers supported their conclusions with a review of recent clinical trials and assembled data from a report by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) covering the years 2006–2009, which included the introduction of continuous-flow technology as well as the original pulsatile flow devices.

Mechanical improvements in failing hearts treated with LVADS have been characterized by partial recovery of the contractile performance of myocytes. This includes improvements of the magnitude of shortening in isolated myocytes in response to beta-adrenergic agonists, of basal relaxation, and in the rise and fall in tension in trabecular muscle preparations.

Relevant markers and pathways found to be improved or normalized by LVAD support included:

Beta-adrenergic signalling. Improvements in developed tension with LVADs have been shown to be associated with an increased beta-adrenergic receptor density. Because a novel combination of LVAD support and pharmacologic therapy – including the selective beta-2 agonist clenbuterol – showed promise in restoring ventricular function in patients with heart failure, investigators analyzed six paired human heart samples isolated at the time of LVAD implantation and at the time of LVAD explantation due to sufficient myocardial recovery. Significant changes to a number of genes in the beta-adrenergic signaling pathway occurred in recovering hearts.

Calcium handling. Although improvements in basal relaxation rates with LVADs have not been definitively linked to changes in calcium handling, the largest improvements in action potential and sarcoplasmic reticulum calcium content occurred in patients who achieved clinical recovery in response to LVADs and pharmacological therapy. However, improvements in calcium handling and contractility appear time dependent, with patients with shorter durations of support (less than 115 days) showing improvement, which reverted back to failing levels in patients with longer durations of support.

Metabolism and growth factor–related genes. Several genes that regulated metabolism were found to change their expression during LVAD-supported recovery. These included arginine:glycine amidinotransferase (AGAT), a rate-limiting enzyme in the creatine synthesis pathway, which was significantly down-regulated after unloading in the recovered hearts, returning to normal levels, in direct contrast to the up-regulation of AGAT seen in patients with heart failure. Insulin growth factor was elevated in patients at the time of LVAD explantation due to recovery. This was thought to aid in limiting atrophy and apoptosis during reverse remodeling and to promote repair and regeneration.

Natriuretic peptides and chromogranin A. Unloading a failing heart with an LVAD was associated with a decrease in natriuretic peptides (which are activated during heart failure) and reestablishment of the local responsiveness of a key enzyme, chromogranin A, to cardiac atrial natriuretic peptide.

But all is not perfect in the LVAD-supported heart. In one study, there was a significant increase in total and cross-linked collagen in the myocardium, compared with nonfailing and medically managed patients with heart failure, which correlated with increased left ventricular stiffness. “Interestingly, the majority of [these] LVAD patients after implantation were not on ACE inhibitors, which have been demonstrated to improve fibrosis and remodeling,” the authors wrote.

A subsequent retrospective cohort study of the same group, comparing LVAD patients who did and did not receive ACE inhibitor therapy after implantation, showed a significant decrease in collagen content and myocardial stiffness in the cohort with LVADs and ACE inhibitors. “These findings support the hypothesis that maximizing optimal medical management after ventricular unloading with LVADs may promote myocardial recovery.”

The study was sponsored by the National Institutes of Health, the American Heart Association, and the National Institutes for Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton and Harefield National Health Service Foundation Trust, and Imperial College London. Several of the authors reported receiving research support and/or honoraria or speakers fees from Thoratec, Heartware Inc., and Medtronic, all manufacturers of LVADs.

Major Finding: The 1-year survival rate improved significantly from 76% in the original HeartMate II trial to 85% in a commercial use trial of the device.

Data Source: A study of 1,496 patients at 83 centers who received the device between April 2008 and September 2010 for bridge to transplantation.

Disclosures: Dr. John disclosed that he received a research grant from Thoratec Corp. to conduct the study. One of the study investigators is employed by the company.

SAN DIEGO – Survival rates of patients implanted with the HeartMate II ventricular assist device have improved significantly, according to a long-term multicenter analysis designed to compare outcomes from the time of the clinical trial to those in the post–Food and Drug Administration approval period.

Excellent outcomes have been maintained and the incidence of adverse events has trended downward with the HeartMate II, a continuous-flow left ventricular assist device (LVAD) for bridge to heart transplantation, Dr. Ranjit John said at the meeting.

A multicenter trial of the HeartMate II, manufactured by Thoratec Corp., was conducted from 2005 to 2008 and led to FDA clearance of the device for bridge to transplantation. Since FDA clearance in April 2008, more than 1,400 additional patients implanted with the device for bridge to transplantation have been tracked by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), which is funded by the National Institutes of Health.

The HeartMate II, also cleared for destination therapy, has been implanted in more than 6,000 patients worldwide, with more than 5,000 patient years of support, according to Dr. John, of the department of cardiothoracic surgery at the University of Minnesota, Minneapolis.

The original trial of the device enrolled 486 bridge to transplantation patients at 36 centers in North America between March 2005 and April 2008. The post-trial commercial use study enrolled 1,496 patients at 83 centers between April 2008 and September 2010. The study's primary end point was survival. Secondary end points included frequency of adverse events and complications, functional status as assessed by the 6-minute walk, and quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire in the original trial and the EuroQol (EQ-5D) instrument in the post trial.

Dr. John reported that the 1-year survival rate improved significantly from 76% in the original trial to 85% in post trial. “With every era of the trial, there was a stepwise incremental improvement in survival, probably from all lessons learned from the early phases of the original trial,” he commented.

The percentage of patients transplanted by 1 year decreased from 48% in the original trial to 39% in the post trial, while the percentage of patients receiving ongoing support increased from 32% in the original trial to 45% in the post trial.

The overall incidences of bleeding and infection in the post trial were 36% and 38%, respectively. Specifically, the incidence of bleeding requiring surgical reexploration was 7%, while the incidence of driveline infections was 13%.

The incidence of adverse events trended downward in the post trial, compared with the original trial. For example, the incidence of bleeding requiring reexploration was 21% in the original trial vs. 7% in the post-trial group. Similar declines were seen in the incidence of percutaneous lead infections (20% vs. 13%, respectively), right heart failure requiring right ventricular assist device (7% vs. 1%), and the need for device replacement (5% vs. 1%).

At baseline, only 13% of patients in the original trial and 16% of patients in the post trial could complete the 6-minute walk test. At 6 months, the proportion of patients who could complete the test improved to 92% and 94%, respectively.

Dr. John also reported that quality of life measures improved in up to 6 months in the original trial and up to 12 months in the post trial.

The invited discussant, Dr. Michael A. Acker, said that the results of the post trial demonstrate “that new VAD technology that utilizes continuous flow – a disruptive concept compared to pulsatile flow – can be taught, along with appropriate patient selection, and can be disseminated to a broad range of clinical centers. If similar successful dissemination occurs after the destination therapy approval, small continuous-flow pumps will constitute a paradigm shift for the treatment of end-stage heart failure.”

Dr. Acker, who heads the cardiovascular surgery division at the University of Pennsylvania Medical Center, Philadelphia, noted that the trial also demonstrates “that mandatory prospective databases such as INTERMACS are essential for monitoring outcomes and providing feedback needed to improve results.”

'With every era of the trial, there was a stepwise incremental improvement in survival.'

Source DR. JOHN

Major Finding: The 1-year survival rate improved significantly from 76% in the original HeartMate II trial to 85% in a commercial use trial of the device.

Data Source: A study of 1,496 patients at 83 centers who received the device between April 2008 and September 2010 for bridge to transplantation.

Disclosures: Dr. John disclosed that he received a research grant from Thoratec Corp. to conduct the study. One of the study investigators is employed by the company.

SAN DIEGO – Survival rates of patients implanted with the HeartMate II ventricular assist device have improved significantly, according to a long-term multicenter analysis designed to compare outcomes from the time of the clinical trial to those in the post–Food and Drug Administration approval period.

Excellent outcomes have been maintained and the incidence of adverse events has trended downward with the HeartMate II, a continuous-flow left ventricular assist device (LVAD) for bridge to heart transplantation, Dr. Ranjit John said at the meeting.

A multicenter trial of the HeartMate II, manufactured by Thoratec Corp., was conducted from 2005 to 2008 and led to FDA clearance of the device for bridge to transplantation. Since FDA clearance in April 2008, more than 1,400 additional patients implanted with the device for bridge to transplantation have been tracked by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), which is funded by the National Institutes of Health.

The HeartMate II, also cleared for destination therapy, has been implanted in more than 6,000 patients worldwide, with more than 5,000 patient years of support, according to Dr. John, of the department of cardiothoracic surgery at the University of Minnesota, Minneapolis.

The original trial of the device enrolled 486 bridge to transplantation patients at 36 centers in North America between March 2005 and April 2008. The post-trial commercial use study enrolled 1,496 patients at 83 centers between April 2008 and September 2010. The study's primary end point was survival. Secondary end points included frequency of adverse events and complications, functional status as assessed by the 6-minute walk, and quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire in the original trial and the EuroQol (EQ-5D) instrument in the post trial.

Dr. John reported that the 1-year survival rate improved significantly from 76% in the original trial to 85% in post trial. “With every era of the trial, there was a stepwise incremental improvement in survival, probably from all lessons learned from the early phases of the original trial,” he commented.

The percentage of patients transplanted by 1 year decreased from 48% in the original trial to 39% in the post trial, while the percentage of patients receiving ongoing support increased from 32% in the original trial to 45% in the post trial.

The overall incidences of bleeding and infection in the post trial were 36% and 38%, respectively. Specifically, the incidence of bleeding requiring surgical reexploration was 7%, while the incidence of driveline infections was 13%.

The incidence of adverse events trended downward in the post trial, compared with the original trial. For example, the incidence of bleeding requiring reexploration was 21% in the original trial vs. 7% in the post-trial group. Similar declines were seen in the incidence of percutaneous lead infections (20% vs. 13%, respectively), right heart failure requiring right ventricular assist device (7% vs. 1%), and the need for device replacement (5% vs. 1%).

At baseline, only 13% of patients in the original trial and 16% of patients in the post trial could complete the 6-minute walk test. At 6 months, the proportion of patients who could complete the test improved to 92% and 94%, respectively.

Dr. John also reported that quality of life measures improved in up to 6 months in the original trial and up to 12 months in the post trial.

The invited discussant, Dr. Michael A. Acker, said that the results of the post trial demonstrate “that new VAD technology that utilizes continuous flow – a disruptive concept compared to pulsatile flow – can be taught, along with appropriate patient selection, and can be disseminated to a broad range of clinical centers. If similar successful dissemination occurs after the destination therapy approval, small continuous-flow pumps will constitute a paradigm shift for the treatment of end-stage heart failure.”

Dr. Acker, who heads the cardiovascular surgery division at the University of Pennsylvania Medical Center, Philadelphia, noted that the trial also demonstrates “that mandatory prospective databases such as INTERMACS are essential for monitoring outcomes and providing feedback needed to improve results.”

'With every era of the trial, there was a stepwise incremental improvement in survival.'

Source DR. JOHN

Major Finding: The 1-year survival rate improved significantly from 76% in the original HeartMate II trial to 85% in a commercial use trial of the device.

Data Source: A study of 1,496 patients at 83 centers who received the device between April 2008 and September 2010 for bridge to transplantation.

Disclosures: Dr. John disclosed that he received a research grant from Thoratec Corp. to conduct the study. One of the study investigators is employed by the company.

SAN DIEGO – Survival rates of patients implanted with the HeartMate II ventricular assist device have improved significantly, according to a long-term multicenter analysis designed to compare outcomes from the time of the clinical trial to those in the post–Food and Drug Administration approval period.

Excellent outcomes have been maintained and the incidence of adverse events has trended downward with the HeartMate II, a continuous-flow left ventricular assist device (LVAD) for bridge to heart transplantation, Dr. Ranjit John said at the meeting.

A multicenter trial of the HeartMate II, manufactured by Thoratec Corp., was conducted from 2005 to 2008 and led to FDA clearance of the device for bridge to transplantation. Since FDA clearance in April 2008, more than 1,400 additional patients implanted with the device for bridge to transplantation have been tracked by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), which is funded by the National Institutes of Health.

The HeartMate II, also cleared for destination therapy, has been implanted in more than 6,000 patients worldwide, with more than 5,000 patient years of support, according to Dr. John, of the department of cardiothoracic surgery at the University of Minnesota, Minneapolis.

The original trial of the device enrolled 486 bridge to transplantation patients at 36 centers in North America between March 2005 and April 2008. The post-trial commercial use study enrolled 1,496 patients at 83 centers between April 2008 and September 2010. The study's primary end point was survival. Secondary end points included frequency of adverse events and complications, functional status as assessed by the 6-minute walk, and quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire in the original trial and the EuroQol (EQ-5D) instrument in the post trial.

Dr. John reported that the 1-year survival rate improved significantly from 76% in the original trial to 85% in post trial. “With every era of the trial, there was a stepwise incremental improvement in survival, probably from all lessons learned from the early phases of the original trial,” he commented.

The percentage of patients transplanted by 1 year decreased from 48% in the original trial to 39% in the post trial, while the percentage of patients receiving ongoing support increased from 32% in the original trial to 45% in the post trial.

The overall incidences of bleeding and infection in the post trial were 36% and 38%, respectively. Specifically, the incidence of bleeding requiring surgical reexploration was 7%, while the incidence of driveline infections was 13%.

The incidence of adverse events trended downward in the post trial, compared with the original trial. For example, the incidence of bleeding requiring reexploration was 21% in the original trial vs. 7% in the post-trial group. Similar declines were seen in the incidence of percutaneous lead infections (20% vs. 13%, respectively), right heart failure requiring right ventricular assist device (7% vs. 1%), and the need for device replacement (5% vs. 1%).

At baseline, only 13% of patients in the original trial and 16% of patients in the post trial could complete the 6-minute walk test. At 6 months, the proportion of patients who could complete the test improved to 92% and 94%, respectively.

Dr. John also reported that quality of life measures improved in up to 6 months in the original trial and up to 12 months in the post trial.

The invited discussant, Dr. Michael A. Acker, said that the results of the post trial demonstrate “that new VAD technology that utilizes continuous flow – a disruptive concept compared to pulsatile flow – can be taught, along with appropriate patient selection, and can be disseminated to a broad range of clinical centers. If similar successful dissemination occurs after the destination therapy approval, small continuous-flow pumps will constitute a paradigm shift for the treatment of end-stage heart failure.”

Dr. Acker, who heads the cardiovascular surgery division at the University of Pennsylvania Medical Center, Philadelphia, noted that the trial also demonstrates “that mandatory prospective databases such as INTERMACS are essential for monitoring outcomes and providing feedback needed to improve results.”

'With every era of the trial, there was a stepwise incremental improvement in survival.'

Source DR. JOHN

Major Finding: In patients who received a cardiac resynchronization device to treat severe heart failure, three different methods for setting the atrioventricular delay – an echocardiographic assessment, a built-in program of the device, and a fixed, 120-msec delay used for all patients – produced no statistically significant differences in the change in left ventricular end systolic volume at 6 months after device placement.

Data Source: The SMART-AV trial, which randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009.

Disclosures: The study was sponsored by Boston Scientific. Dr. Ellenbogen said that he has served as a consultant or an advisory board member to, lectured on behalf of, and/or received research grants from, Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group, Cardionet, Atricare, EBR, Sanofi-Aventis, and Biosense Webster. Dr. Tomaselli said that he had no disclosures.

CHICAGO – The standard, atrioventricular delay built into many cardiac resynchronization devices worked as effectively as did an automated patient-tailored delay or a delay based on a time-consuming echocardiography assessment in a randomized trial that involved nearly 1,000 patients.

“The routine use of AV [atrioventricular] optimization techniques assessed in this trial is not warranted,” Dr. Kenneth A. Ellenbogen said at the meeting. But it may help patients who don't initially respond to cardiac resynchronization therapy (CRT), he added, although the results he reported did not assess this possibility.

The findings refuted a recommendation made in 2008 by a panel of the American Society of Echocardiography to routinely use an echo assessment to set the AV delay in patients receiving a CRT device (J. Am. Soc. Echocardiogr. 2008;21:191-213).

“The algorithms [for determining an optimal AV delay] made excellent sense hemodynamically, but you need a clinical trial to look at clinical outcomes,” said Dr. Ellenbogen, vice-chairman of cardiology and director of clinical cardiac electrophysiology and pacing at Virginia Commonwealth University in Richmond, Va.

“The bottom line is we can save patients an expensive and time-consuming study that really doesn't benefit the majority of patients. The out-of-the-box settings seem to work in most patients,” he added.

A detailed echo study “is about an hour long and uses resources,” and was no better than the alternatives, commented Dr. Gordon F. Tomaselli, professor and chief of cardiology at Johns Hopkins University in Baltimore. “The key comparison of the study was do we need to do a detailed echo study on everyone to optimize the hemodynamics, and the answer was no,” he said in an interview.

The results also called into question the usefulness of a feature in all CRT devices on the U.S. market that automatically attempts to optimize the AV delay based on what the device detects as the patient's intrinsic AV interval and baseline QRS width. In the Boston Scientific CRT unit used in the new study, this feature is called “SmartDelay.” The study results showed no stagnificant benefit from the SmartDelay feature compared with a fixed AV delay of 120 msec for all patients.

“All the companies have their algorithms” for setting the AV delay, said Dr. Tomaselli. He also noted that while the new results showed no significant difference between the fixed delay of 120 msec and the variable delays applied by the device's built-in programming function, several outcomes showed trends toward superiority using the built-in program.

For example, in the study's primary outcome – the median change in left ventricular end systolic volume at 6 months after placement of the CRT device – the results showed a median 21-mL reduction in patients whose delay got set by the device's internal program (which produced an average delay of 48 msec) and a median 15-mL reduction in patients who received a device set to the fixed, 120-msec delay. Patients who underwent an echo-guided procedure to set the delay had a median reduction of 19 mL.

The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) trial randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009. The researchers were able to perform follow-up assessments on 86% of the randomized patients. The patients' average age was 66, two-thirds were men, and more than 90% had New York Heart Association class III heart failure.

The study's secondary outcomes analyses also showed no significant differences between the three methods used to set the AV delay for changes in left ventricular end diastolic volume, ejection fraction, 6-minute walk, quality of life, or NYHA heart failure class. A series of post hoc subgroup analyses also generally showed no differenceinetween the three methods. These included patients with ischemic or nonischemic heart failure etiology, patients with either greater or less than 30% atrial pacing, patients with or without bundle branch block, and those with a QRS duration of less than 150 msec and those with a duration of at least 150 msec.

The only subgroup that showed a differential effect was in women, who had a significantly better response to either the device-selected AV delay or an echo-guided delay compared with the fixed, 120-msec delay. In men, the three approaches had identical effects. The implications of this finding for selecting a CRT delay in women will need further study, Dr. Ellenbogen said. He also stressed the need to compare the efficacy of the three delay-setting approaches in the roughly 25% of patients who don't initially respond to their CRT device.

Concurrently with Dr. Ellenbogen's report at the meeting, the results were published online (Circulation 2010 Nov. 15 [doi:10.1161/circulationaha.110.992552]).

Major Finding: In patients who received a cardiac resynchronization device to treat severe heart failure, three different methods for setting the atrioventricular delay – an echocardiographic assessment, a built-in program of the device, and a fixed, 120-msec delay used for all patients – produced no statistically significant differences in the change in left ventricular end systolic volume at 6 months after device placement.

Data Source: The SMART-AV trial, which randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009.

Disclosures: The study was sponsored by Boston Scientific. Dr. Ellenbogen said that he has served as a consultant or an advisory board member to, lectured on behalf of, and/or received research grants from, Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group, Cardionet, Atricare, EBR, Sanofi-Aventis, and Biosense Webster. Dr. Tomaselli said that he had no disclosures.

CHICAGO – The standard, atrioventricular delay built into many cardiac resynchronization devices worked as effectively as did an automated patient-tailored delay or a delay based on a time-consuming echocardiography assessment in a randomized trial that involved nearly 1,000 patients.

“The routine use of AV [atrioventricular] optimization techniques assessed in this trial is not warranted,” Dr. Kenneth A. Ellenbogen said at the meeting. But it may help patients who don't initially respond to cardiac resynchronization therapy (CRT), he added, although the results he reported did not assess this possibility.

The findings refuted a recommendation made in 2008 by a panel of the American Society of Echocardiography to routinely use an echo assessment to set the AV delay in patients receiving a CRT device (J. Am. Soc. Echocardiogr. 2008;21:191-213).

“The algorithms [for determining an optimal AV delay] made excellent sense hemodynamically, but you need a clinical trial to look at clinical outcomes,” said Dr. Ellenbogen, vice-chairman of cardiology and director of clinical cardiac electrophysiology and pacing at Virginia Commonwealth University in Richmond, Va.

“The bottom line is we can save patients an expensive and time-consuming study that really doesn't benefit the majority of patients. The out-of-the-box settings seem to work in most patients,” he added.

A detailed echo study “is about an hour long and uses resources,” and was no better than the alternatives, commented Dr. Gordon F. Tomaselli, professor and chief of cardiology at Johns Hopkins University in Baltimore. “The key comparison of the study was do we need to do a detailed echo study on everyone to optimize the hemodynamics, and the answer was no,” he said in an interview.

The results also called into question the usefulness of a feature in all CRT devices on the U.S. market that automatically attempts to optimize the AV delay based on what the device detects as the patient's intrinsic AV interval and baseline QRS width. In the Boston Scientific CRT unit used in the new study, this feature is called “SmartDelay.” The study results showed no stagnificant benefit from the SmartDelay feature compared with a fixed AV delay of 120 msec for all patients.

“All the companies have their algorithms” for setting the AV delay, said Dr. Tomaselli. He also noted that while the new results showed no significant difference between the fixed delay of 120 msec and the variable delays applied by the device's built-in programming function, several outcomes showed trends toward superiority using the built-in program.

For example, in the study's primary outcome – the median change in left ventricular end systolic volume at 6 months after placement of the CRT device – the results showed a median 21-mL reduction in patients whose delay got set by the device's internal program (which produced an average delay of 48 msec) and a median 15-mL reduction in patients who received a device set to the fixed, 120-msec delay. Patients who underwent an echo-guided procedure to set the delay had a median reduction of 19 mL.

The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) trial randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009. The researchers were able to perform follow-up assessments on 86% of the randomized patients. The patients' average age was 66, two-thirds were men, and more than 90% had New York Heart Association class III heart failure.

The study's secondary outcomes analyses also showed no significant differences between the three methods used to set the AV delay for changes in left ventricular end diastolic volume, ejection fraction, 6-minute walk, quality of life, or NYHA heart failure class. A series of post hoc subgroup analyses also generally showed no differenceinetween the three methods. These included patients with ischemic or nonischemic heart failure etiology, patients with either greater or less than 30% atrial pacing, patients with or without bundle branch block, and those with a QRS duration of less than 150 msec and those with a duration of at least 150 msec.

The only subgroup that showed a differential effect was in women, who had a significantly better response to either the device-selected AV delay or an echo-guided delay compared with the fixed, 120-msec delay. In men, the three approaches had identical effects. The implications of this finding for selecting a CRT delay in women will need further study, Dr. Ellenbogen said. He also stressed the need to compare the efficacy of the three delay-setting approaches in the roughly 25% of patients who don't initially respond to their CRT device.

Concurrently with Dr. Ellenbogen's report at the meeting, the results were published online (Circulation 2010 Nov. 15 [doi:10.1161/circulationaha.110.992552]).

Major Finding: In patients who received a cardiac resynchronization device to treat severe heart failure, three different methods for setting the atrioventricular delay – an echocardiographic assessment, a built-in program of the device, and a fixed, 120-msec delay used for all patients – produced no statistically significant differences in the change in left ventricular end systolic volume at 6 months after device placement.

Data Source: The SMART-AV trial, which randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009.

Disclosures: The study was sponsored by Boston Scientific. Dr. Ellenbogen said that he has served as a consultant or an advisory board member to, lectured on behalf of, and/or received research grants from, Boston Scientific, Biotronik, Medtronic, St. Jude Medical, Sorin Group, Cardionet, Atricare, EBR, Sanofi-Aventis, and Biosense Webster. Dr. Tomaselli said that he had no disclosures.

CHICAGO – The standard, atrioventricular delay built into many cardiac resynchronization devices worked as effectively as did an automated patient-tailored delay or a delay based on a time-consuming echocardiography assessment in a randomized trial that involved nearly 1,000 patients.

“The routine use of AV [atrioventricular] optimization techniques assessed in this trial is not warranted,” Dr. Kenneth A. Ellenbogen said at the meeting. But it may help patients who don't initially respond to cardiac resynchronization therapy (CRT), he added, although the results he reported did not assess this possibility.

The findings refuted a recommendation made in 2008 by a panel of the American Society of Echocardiography to routinely use an echo assessment to set the AV delay in patients receiving a CRT device (J. Am. Soc. Echocardiogr. 2008;21:191-213).

“The algorithms [for determining an optimal AV delay] made excellent sense hemodynamically, but you need a clinical trial to look at clinical outcomes,” said Dr. Ellenbogen, vice-chairman of cardiology and director of clinical cardiac electrophysiology and pacing at Virginia Commonwealth University in Richmond, Va.

“The bottom line is we can save patients an expensive and time-consuming study that really doesn't benefit the majority of patients. The out-of-the-box settings seem to work in most patients,” he added.

A detailed echo study “is about an hour long and uses resources,” and was no better than the alternatives, commented Dr. Gordon F. Tomaselli, professor and chief of cardiology at Johns Hopkins University in Baltimore. “The key comparison of the study was do we need to do a detailed echo study on everyone to optimize the hemodynamics, and the answer was no,” he said in an interview.

The results also called into question the usefulness of a feature in all CRT devices on the U.S. market that automatically attempts to optimize the AV delay based on what the device detects as the patient's intrinsic AV interval and baseline QRS width. In the Boston Scientific CRT unit used in the new study, this feature is called “SmartDelay.” The study results showed no stagnificant benefit from the SmartDelay feature compared with a fixed AV delay of 120 msec for all patients.

“All the companies have their algorithms” for setting the AV delay, said Dr. Tomaselli. He also noted that while the new results showed no significant difference between the fixed delay of 120 msec and the variable delays applied by the device's built-in programming function, several outcomes showed trends toward superiority using the built-in program.

For example, in the study's primary outcome – the median change in left ventricular end systolic volume at 6 months after placement of the CRT device – the results showed a median 21-mL reduction in patients whose delay got set by the device's internal program (which produced an average delay of 48 msec) and a median 15-mL reduction in patients who received a device set to the fixed, 120-msec delay. Patients who underwent an echo-guided procedure to set the delay had a median reduction of 19 mL.

The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) trial randomized and implanted 980 patients at 100 centers in the United States and Europe during May 2008–December 2009. The researchers were able to perform follow-up assessments on 86% of the randomized patients. The patients' average age was 66, two-thirds were men, and more than 90% had New York Heart Association class III heart failure.

The study's secondary outcomes analyses also showed no significant differences between the three methods used to set the AV delay for changes in left ventricular end diastolic volume, ejection fraction, 6-minute walk, quality of life, or NYHA heart failure class. A series of post hoc subgroup analyses also generally showed no differenceinetween the three methods. These included patients with ischemic or nonischemic heart failure etiology, patients with either greater or less than 30% atrial pacing, patients with or without bundle branch block, and those with a QRS duration of less than 150 msec and those with a duration of at least 150 msec.

The only subgroup that showed a differential effect was in women, who had a significantly better response to either the device-selected AV delay or an echo-guided delay compared with the fixed, 120-msec delay. In men, the three approaches had identical effects. The implications of this finding for selecting a CRT delay in women will need further study, Dr. Ellenbogen said. He also stressed the need to compare the efficacy of the three delay-setting approaches in the roughly 25% of patients who don't initially respond to their CRT device.

Concurrently with Dr. Ellenbogen's report at the meeting, the results were published online (Circulation 2010 Nov. 15 [doi:10.1161/circulationaha.110.992552]).

CHICAGO – A high-normal hematocrit was associated with an increased risk of new-onset heart failure in a Framingham Heart Study analysis.

“To our knowledge, this is the only study to show such a relationship in men and women in middle age. … Our results should prompt consideration of a cautious and measured approach to the aggressive treatment of low hematocrit in a variety of disease states,” Dr. Erin E. Coglianese said at the meeting.

The mechanism by which a hematocrit (HCT) within normal range is linked to heart failure is unclear. However, animal studies suggest one possibility – that a high-normal HCT could impair vasodilation owing to scavenging of nitric oxide by hemoglobin, said Dr. Coglianese of Massachusetts General Hospital, Boston.

To explore the relationship between HCT and risk of heart failure, she and her colleagues turned to the Framingham Heart Study. They documented a strong, graded relationship between HCT level and the risk of developing heart failure in 3,523 Framingham participants aged 50-65 who were free of a history of heart failure at baseline and were followed for up to 20 years.

Indeed, individuals with a high-normal baseline HCT had almost double the risk of new-onset heart failure during follow-up, compared with those with a low HCT, even after adjustment for conventional risk factors for heart failure.

A low HCT was defined as 39% to less than 44% in men and 36% to less than 40% in women. Men with an HCT of 44% to less than 46% and women with a level of 40% to less than 42% were deemed as having a low-normal level. A normal HCT was defined as 46% to less than 50% in men and 42% to less than 46% in women. And a high-normal HCT was one greater than 50% in men or 46% in women.

When these definitions were used, the incidence of new-onset heart failure was 25/10,000 person-years in people with a low HCT level, 31/10,000 with a low-normal HCT, 38/10,000 with a normal HCT, and 48/10,000 in Framingham participants with high-normal HCT.

Analysis, showed that the risk of new-onset heart failure, compared with the risk in those with a low HCT, was 27% greater in those with a low-normal HCT, 47% greater in those with a normal HCT, and 78% greater in those with a high-normal level. The analysis was adjusted for age, sex, total cholesterol, hypertension, body mass index, left ventricular hypertrophy, pack-years of smoking, and physical activity.

The big limitation of this study is that the original Framingham cohort, included in this analysis, looks in some ways quite different from contemporary patient populations. Specifically, roughly half of the men in the original cohort were smokers, Dr. Coglianese noted.

In contrast to these new findings, many studies have shown that in patients who already have heart failure, a low HCT is associated with an increased risk of heart failure hospitalization and all-cause mortality. It is unclear whether this increased risk is due to changes induced by low HCT, or if low HCT is a marker of disease severity, she said.

Dr. Coglianese said he had no relevant financial disclosures.

CHICAGO – A high-normal hematocrit was associated with an increased risk of new-onset heart failure in a Framingham Heart Study analysis.

“To our knowledge, this is the only study to show such a relationship in men and women in middle age. … Our results should prompt consideration of a cautious and measured approach to the aggressive treatment of low hematocrit in a variety of disease states,” Dr. Erin E. Coglianese said at the meeting.

The mechanism by which a hematocrit (HCT) within normal range is linked to heart failure is unclear. However, animal studies suggest one possibility – that a high-normal HCT could impair vasodilation owing to scavenging of nitric oxide by hemoglobin, said Dr. Coglianese of Massachusetts General Hospital, Boston.

To explore the relationship between HCT and risk of heart failure, she and her colleagues turned to the Framingham Heart Study. They documented a strong, graded relationship between HCT level and the risk of developing heart failure in 3,523 Framingham participants aged 50-65 who were free of a history of heart failure at baseline and were followed for up to 20 years.

Indeed, individuals with a high-normal baseline HCT had almost double the risk of new-onset heart failure during follow-up, compared with those with a low HCT, even after adjustment for conventional risk factors for heart failure.

A low HCT was defined as 39% to less than 44% in men and 36% to less than 40% in women. Men with an HCT of 44% to less than 46% and women with a level of 40% to less than 42% were deemed as having a low-normal level. A normal HCT was defined as 46% to less than 50% in men and 42% to less than 46% in women. And a high-normal HCT was one greater than 50% in men or 46% in women.

When these definitions were used, the incidence of new-onset heart failure was 25/10,000 person-years in people with a low HCT level, 31/10,000 with a low-normal HCT, 38/10,000 with a normal HCT, and 48/10,000 in Framingham participants with high-normal HCT.

Analysis, showed that the risk of new-onset heart failure, compared with the risk in those with a low HCT, was 27% greater in those with a low-normal HCT, 47% greater in those with a normal HCT, and 78% greater in those with a high-normal level. The analysis was adjusted for age, sex, total cholesterol, hypertension, body mass index, left ventricular hypertrophy, pack-years of smoking, and physical activity.

The big limitation of this study is that the original Framingham cohort, included in this analysis, looks in some ways quite different from contemporary patient populations. Specifically, roughly half of the men in the original cohort were smokers, Dr. Coglianese noted.

In contrast to these new findings, many studies have shown that in patients who already have heart failure, a low HCT is associated with an increased risk of heart failure hospitalization and all-cause mortality. It is unclear whether this increased risk is due to changes induced by low HCT, or if low HCT is a marker of disease severity, she said.

Dr. Coglianese said he had no relevant financial disclosures.

CHICAGO – A high-normal hematocrit was associated with an increased risk of new-onset heart failure in a Framingham Heart Study analysis.

“To our knowledge, this is the only study to show such a relationship in men and women in middle age. … Our results should prompt consideration of a cautious and measured approach to the aggressive treatment of low hematocrit in a variety of disease states,” Dr. Erin E. Coglianese said at the meeting.

The mechanism by which a hematocrit (HCT) within normal range is linked to heart failure is unclear. However, animal studies suggest one possibility – that a high-normal HCT could impair vasodilation owing to scavenging of nitric oxide by hemoglobin, said Dr. Coglianese of Massachusetts General Hospital, Boston.

To explore the relationship between HCT and risk of heart failure, she and her colleagues turned to the Framingham Heart Study. They documented a strong, graded relationship between HCT level and the risk of developing heart failure in 3,523 Framingham participants aged 50-65 who were free of a history of heart failure at baseline and were followed for up to 20 years.

Indeed, individuals with a high-normal baseline HCT had almost double the risk of new-onset heart failure during follow-up, compared with those with a low HCT, even after adjustment for conventional risk factors for heart failure.

A low HCT was defined as 39% to less than 44% in men and 36% to less than 40% in women. Men with an HCT of 44% to less than 46% and women with a level of 40% to less than 42% were deemed as having a low-normal level. A normal HCT was defined as 46% to less than 50% in men and 42% to less than 46% in women. And a high-normal HCT was one greater than 50% in men or 46% in women.

When these definitions were used, the incidence of new-onset heart failure was 25/10,000 person-years in people with a low HCT level, 31/10,000 with a low-normal HCT, 38/10,000 with a normal HCT, and 48/10,000 in Framingham participants with high-normal HCT.

Analysis, showed that the risk of new-onset heart failure, compared with the risk in those with a low HCT, was 27% greater in those with a low-normal HCT, 47% greater in those with a normal HCT, and 78% greater in those with a high-normal level. The analysis was adjusted for age, sex, total cholesterol, hypertension, body mass index, left ventricular hypertrophy, pack-years of smoking, and physical activity.

The big limitation of this study is that the original Framingham cohort, included in this analysis, looks in some ways quite different from contemporary patient populations. Specifically, roughly half of the men in the original cohort were smokers, Dr. Coglianese noted.

In contrast to these new findings, many studies have shown that in patients who already have heart failure, a low HCT is associated with an increased risk of heart failure hospitalization and all-cause mortality. It is unclear whether this increased risk is due to changes induced by low HCT, or if low HCT is a marker of disease severity, she said.

Dr. Coglianese said he had no relevant financial disclosures.