Heart Failure

NEW ORLEANS — In the largest study of exercise training as part of the management of heart failure to date, a guided exercise program was safe and modestly effective, although investigators acknowledged that patients found it hard to keep up the routine.

The safety of exercise training in heart failure patients, outside of a supervised environment, has been a concern, but this study proved benefits could be obtained without excess risk, said Dr. Christopher M. O'Connor, presenting results of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial at the annual scientific sessions of the American Heart Association.

“Over 30 randomized trials have shown increased exercise capacity and possibly improved survival with exercise training, but these were largely single-center studies that were underpowered or lacked adequate controls and produced limited data on safety,” he noted at a press conference.

HF-ACTION, a randomized, phase III trial sponsored by the National Heart, Lung, and Blood Institute, followed 2,331 heart failure patients at 82 international sites for an average of 2.5 years. The relatively young population, median age 59 years, had an average left ventricular ejection fraction (LVEF) of 25%, indicating moderate HF. History of coronary occlusion and prior myocardial infarction was common.

Patients were randomized to an exercise training program aimed at increasing workout intensity and duration or to usual care, where they were encouraged to exercise, based on the American College of Cardiology/AHA recommendations of 30 minutes of moderate exercise most days of the week. Both groups received optimized medical treatment, patient education, and follow-up phone calls.

The exercise training followed the cardiac rehabilitation model. Patients were prescribed a multistage, guided workout of 36 supervised training sessions of 30 minutes of exercise three times a week. At the 18th session, patients received a treadmill or exercise bicycle for home use, learned how to monitor their heart rate during exercise, and were encouraged to complete five weekly sessions of similar intensity and 40 minutes' duration.

At 4–6 weeks, patients were exercising a median of 95 minutes per week, a little short of the goal of 120 minutes. This was consistent for the first year and then diminished further, reported Dr. O'Connor, professor of medicine and director of the heart center at Duke University Medical Center, Durham, N.C.

The diminished adherence is not surprising, he said, because “lifestyle intervention trials are very difficult. At the completion of a drug trial, for example, 85% of patients would still be on the drug. Here, after 3 years people were exercising for about 50 minutes. We had wanted them to exercise for 120 minutes. So adherence is extremely difficult.”

Exercise training was not associated with a significant reduction in the primary end point, all-cause mortality and hospitalization. Adjusted for heart failure etiology, this group experienced a 7% relative risk reduction that was not statistically significant. Secondary composite end points also failed to reach significance: cardiovascular (CV) mortality plus CV hospitalization was reduced by 8%, and CV mortality plus HF hospitalization was reduced by 13%, Dr. O'Connor reported.

However, improvements in outcomes emerged in the prespecified adjusted analysis that accounted for additional key prognostic variables related to heart failure outcomes. These included exercise duration, LVEF, Beck Depression Inventory score, and history of atrial fibrillation flutter.

In the adjusted analysis, the primary end point was significantly reduced by 11%, and CV mortality plus heart failure hospitalization was significantly reduced by 15%. The reduction in CV mortality plus CV hospitalization remained a nonsignificant 8%.

“The prespecified adjusted analysis is a fair analysis of these data and is probably closest to the truth,” Dr. O'Connor maintained. “Prognostic factors are most important. The reductions in risk were in the range of 11%–15%.”

The study found no excess risk for CV events or fractures with intensive exercise. “Perhaps the most important finding is that exercise training of this degree was safe,” Dr. O'Connor added. There was no increase in CV events or fractures with intensive exercise.

The improvements in outcomes were obtained in a setting of excellent overall cardiac care, he added, as more than 90% of patients received evidence-based medical therapy for their disease. “We achieved an 11%–15% meaningful reduction in clinical end points above that, with a safe intervention,” he emphasized.

Discussant Dr. Philip Poole-Wilson said, “This study stresses that the advice to exercise is correct and important. Now, how to persuade the patient is harder.”

“The study missed the primary end point, and some would say that's the end of it. But that would be wrong,” said Dr. Poole-Wilson, professor of medicine at the Imperial College London. “After adjustments, it met many end points, and this means it was a positive trial. The study supports the use of exercise and will strengthen guidelines for the treatment of heart failure, which has wide implications.”

Dr. Clyde Yancy spoke to the financial implications of the study in an interview. He pointed out that the paradigm for exercise has long been established in the form of the cardiac rehabilitation model in which patients enroll in a program over 9–12 weeks to define a new lifestyle,” he said. “When exercise emanates from a structured rehab program, it quadruples adherence rates.

“The important question is whether the study data are sufficient to say that enrollment in a rehab program should become an evidence-based treatment strategy in heart failure. Because if it is guideline-generated then the expectation is that CMS and payers would cover the cost,” said Dr. Yancy, medical director of Baylor University, Dallas.

NEW ORLEANS — In the largest study of exercise training as part of the management of heart failure to date, a guided exercise program was safe and modestly effective, although investigators acknowledged that patients found it hard to keep up the routine.

The safety of exercise training in heart failure patients, outside of a supervised environment, has been a concern, but this study proved benefits could be obtained without excess risk, said Dr. Christopher M. O'Connor, presenting results of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial at the annual scientific sessions of the American Heart Association.

“Over 30 randomized trials have shown increased exercise capacity and possibly improved survival with exercise training, but these were largely single-center studies that were underpowered or lacked adequate controls and produced limited data on safety,” he noted at a press conference.

HF-ACTION, a randomized, phase III trial sponsored by the National Heart, Lung, and Blood Institute, followed 2,331 heart failure patients at 82 international sites for an average of 2.5 years. The relatively young population, median age 59 years, had an average left ventricular ejection fraction (LVEF) of 25%, indicating moderate HF. History of coronary occlusion and prior myocardial infarction was common.

Patients were randomized to an exercise training program aimed at increasing workout intensity and duration or to usual care, where they were encouraged to exercise, based on the American College of Cardiology/AHA recommendations of 30 minutes of moderate exercise most days of the week. Both groups received optimized medical treatment, patient education, and follow-up phone calls.

The exercise training followed the cardiac rehabilitation model. Patients were prescribed a multistage, guided workout of 36 supervised training sessions of 30 minutes of exercise three times a week. At the 18th session, patients received a treadmill or exercise bicycle for home use, learned how to monitor their heart rate during exercise, and were encouraged to complete five weekly sessions of similar intensity and 40 minutes' duration.

At 4–6 weeks, patients were exercising a median of 95 minutes per week, a little short of the goal of 120 minutes. This was consistent for the first year and then diminished further, reported Dr. O'Connor, professor of medicine and director of the heart center at Duke University Medical Center, Durham, N.C.

The diminished adherence is not surprising, he said, because “lifestyle intervention trials are very difficult. At the completion of a drug trial, for example, 85% of patients would still be on the drug. Here, after 3 years people were exercising for about 50 minutes. We had wanted them to exercise for 120 minutes. So adherence is extremely difficult.”

Exercise training was not associated with a significant reduction in the primary end point, all-cause mortality and hospitalization. Adjusted for heart failure etiology, this group experienced a 7% relative risk reduction that was not statistically significant. Secondary composite end points also failed to reach significance: cardiovascular (CV) mortality plus CV hospitalization was reduced by 8%, and CV mortality plus HF hospitalization was reduced by 13%, Dr. O'Connor reported.

However, improvements in outcomes emerged in the prespecified adjusted analysis that accounted for additional key prognostic variables related to heart failure outcomes. These included exercise duration, LVEF, Beck Depression Inventory score, and history of atrial fibrillation flutter.

In the adjusted analysis, the primary end point was significantly reduced by 11%, and CV mortality plus heart failure hospitalization was significantly reduced by 15%. The reduction in CV mortality plus CV hospitalization remained a nonsignificant 8%.

“The prespecified adjusted analysis is a fair analysis of these data and is probably closest to the truth,” Dr. O'Connor maintained. “Prognostic factors are most important. The reductions in risk were in the range of 11%–15%.”

The study found no excess risk for CV events or fractures with intensive exercise. “Perhaps the most important finding is that exercise training of this degree was safe,” Dr. O'Connor added. There was no increase in CV events or fractures with intensive exercise.

The improvements in outcomes were obtained in a setting of excellent overall cardiac care, he added, as more than 90% of patients received evidence-based medical therapy for their disease. “We achieved an 11%–15% meaningful reduction in clinical end points above that, with a safe intervention,” he emphasized.

Discussant Dr. Philip Poole-Wilson said, “This study stresses that the advice to exercise is correct and important. Now, how to persuade the patient is harder.”

“The study missed the primary end point, and some would say that's the end of it. But that would be wrong,” said Dr. Poole-Wilson, professor of medicine at the Imperial College London. “After adjustments, it met many end points, and this means it was a positive trial. The study supports the use of exercise and will strengthen guidelines for the treatment of heart failure, which has wide implications.”

Dr. Clyde Yancy spoke to the financial implications of the study in an interview. He pointed out that the paradigm for exercise has long been established in the form of the cardiac rehabilitation model in which patients enroll in a program over 9–12 weeks to define a new lifestyle,” he said. “When exercise emanates from a structured rehab program, it quadruples adherence rates.

“The important question is whether the study data are sufficient to say that enrollment in a rehab program should become an evidence-based treatment strategy in heart failure. Because if it is guideline-generated then the expectation is that CMS and payers would cover the cost,” said Dr. Yancy, medical director of Baylor University, Dallas.

NEW ORLEANS — In the largest study of exercise training as part of the management of heart failure to date, a guided exercise program was safe and modestly effective, although investigators acknowledged that patients found it hard to keep up the routine.

The safety of exercise training in heart failure patients, outside of a supervised environment, has been a concern, but this study proved benefits could be obtained without excess risk, said Dr. Christopher M. O'Connor, presenting results of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) trial at the annual scientific sessions of the American Heart Association.

“Over 30 randomized trials have shown increased exercise capacity and possibly improved survival with exercise training, but these were largely single-center studies that were underpowered or lacked adequate controls and produced limited data on safety,” he noted at a press conference.

HF-ACTION, a randomized, phase III trial sponsored by the National Heart, Lung, and Blood Institute, followed 2,331 heart failure patients at 82 international sites for an average of 2.5 years. The relatively young population, median age 59 years, had an average left ventricular ejection fraction (LVEF) of 25%, indicating moderate HF. History of coronary occlusion and prior myocardial infarction was common.

Patients were randomized to an exercise training program aimed at increasing workout intensity and duration or to usual care, where they were encouraged to exercise, based on the American College of Cardiology/AHA recommendations of 30 minutes of moderate exercise most days of the week. Both groups received optimized medical treatment, patient education, and follow-up phone calls.

The exercise training followed the cardiac rehabilitation model. Patients were prescribed a multistage, guided workout of 36 supervised training sessions of 30 minutes of exercise three times a week. At the 18th session, patients received a treadmill or exercise bicycle for home use, learned how to monitor their heart rate during exercise, and were encouraged to complete five weekly sessions of similar intensity and 40 minutes' duration.

At 4–6 weeks, patients were exercising a median of 95 minutes per week, a little short of the goal of 120 minutes. This was consistent for the first year and then diminished further, reported Dr. O'Connor, professor of medicine and director of the heart center at Duke University Medical Center, Durham, N.C.

The diminished adherence is not surprising, he said, because “lifestyle intervention trials are very difficult. At the completion of a drug trial, for example, 85% of patients would still be on the drug. Here, after 3 years people were exercising for about 50 minutes. We had wanted them to exercise for 120 minutes. So adherence is extremely difficult.”

Exercise training was not associated with a significant reduction in the primary end point, all-cause mortality and hospitalization. Adjusted for heart failure etiology, this group experienced a 7% relative risk reduction that was not statistically significant. Secondary composite end points also failed to reach significance: cardiovascular (CV) mortality plus CV hospitalization was reduced by 8%, and CV mortality plus HF hospitalization was reduced by 13%, Dr. O'Connor reported.

However, improvements in outcomes emerged in the prespecified adjusted analysis that accounted for additional key prognostic variables related to heart failure outcomes. These included exercise duration, LVEF, Beck Depression Inventory score, and history of atrial fibrillation flutter.

In the adjusted analysis, the primary end point was significantly reduced by 11%, and CV mortality plus heart failure hospitalization was significantly reduced by 15%. The reduction in CV mortality plus CV hospitalization remained a nonsignificant 8%.

“The prespecified adjusted analysis is a fair analysis of these data and is probably closest to the truth,” Dr. O'Connor maintained. “Prognostic factors are most important. The reductions in risk were in the range of 11%–15%.”

The study found no excess risk for CV events or fractures with intensive exercise. “Perhaps the most important finding is that exercise training of this degree was safe,” Dr. O'Connor added. There was no increase in CV events or fractures with intensive exercise.

The improvements in outcomes were obtained in a setting of excellent overall cardiac care, he added, as more than 90% of patients received evidence-based medical therapy for their disease. “We achieved an 11%–15% meaningful reduction in clinical end points above that, with a safe intervention,” he emphasized.

Discussant Dr. Philip Poole-Wilson said, “This study stresses that the advice to exercise is correct and important. Now, how to persuade the patient is harder.”

“The study missed the primary end point, and some would say that's the end of it. But that would be wrong,” said Dr. Poole-Wilson, professor of medicine at the Imperial College London. “After adjustments, it met many end points, and this means it was a positive trial. The study supports the use of exercise and will strengthen guidelines for the treatment of heart failure, which has wide implications.”

Dr. Clyde Yancy spoke to the financial implications of the study in an interview. He pointed out that the paradigm for exercise has long been established in the form of the cardiac rehabilitation model in which patients enroll in a program over 9–12 weeks to define a new lifestyle,” he said. “When exercise emanates from a structured rehab program, it quadruples adherence rates.

“The important question is whether the study data are sufficient to say that enrollment in a rehab program should become an evidence-based treatment strategy in heart failure. Because if it is guideline-generated then the expectation is that CMS and payers would cover the cost,” said Dr. Yancy, medical director of Baylor University, Dallas.

NEW ORLEANS — Heart failure patients with preserved systolic function did not benefit from treatment with an angiotensin II receptor blocker, according to results of the I-PRESERVE trial, the world's largest placebo-controlled trial of an ARB.

“Disappointingly, for this large group of patients—almost half the patients with heart failure—there remains no specific evidence-based therapy,” concluded Dr. Barry M. Massie, who presented the results of the Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) trial at the annual scientific sessions of the American Heart Association.

Although no pharmacologic therapy has been shown to be effective in improving outcomes in this type of heart failure, inhibitors of the renin-angiotensin-aldosterone system have been of interest because that system is involved in many of the processes associated with this syndrome, such as hypertension, left ventricular hypertrophy, myocardial fibrosis, and vascular dysfunction. Previous studies have hinted at benefits from ARBs and from ACE inhibitors, but statistically significant improvements have not been established, said Dr. Massie, professor of medicine at the University of California, San Francisco and chief of cardiology at the San Francisco Veterans Affairs Medical Center.

I-PRESERVE included 4,128 patients with class II-IV heart failure and a left ventricular ejection fraction of at least 45%. The population was similar to that seen in prior epidemiologic studies in several important ways. The patients were mostly women, were elderly (median age 72 years), and about 9 of 10 had a history of hypertension. The average left ventricular ejection fraction was 59%.

Patients were randomized to either irbesartan up to 300 mg daily or usual care (placebo). The primary end point was a composite of all-cause death, hospitalization for heart failure, myocardial infarction, unstable angina, arrhythmia, and stroke.

After a mean follow-up of approximately 4 years, the primary outcome rates were nearly identical, occurring in 36% (742 of 2,067) of the irbesartan patients and 37% (763 of 2,061) of the placebo group. Similarly, there were no significant differences in the major secondary end points of cardiovascular death and death or hospitalization due to heart failure, or in any of the eight prespecified subgroups, Dr. Massie reported.

“Irbesartan was unsuccessful in achieving its primary or secondary outcomes,” Dr. Massie announced. The results are consistent with two previous trials in patients with heart failure and preserved ejection fraction that did not show a positive treatment effect with either candesartan or perindopril, he added.

Dr. Massie acknowledged that this was a “very well treated population,” with most patients receiving diuretics and many receiving other medications. “After randomization, there was an intensification of all these therapies,” he observed, explaining that this can confound outcomes.

“For this field to move forward, we need a better understanding of the mechanisms underlying this syndrome, and we need to find potential targets above and beyond those used for low ejection fraction patients. We need to do something. This affects more than 2 million individuals in the United States alone.”

Dr. Margaret M. Redfield, professor of medicine at the Mayo Clinic, Rochester, Minn., called I-PRESERVE, “a very important trial, if only for the fact that ARBs and ACE inhibitors are already widely used for the treatment of heart failure with preserved ejection fraction, even though no randomized trial has shown a benefit. Two huge registries have shown that 60% are treated with these agents despite the lack of evidence.”

In this form of heart failure, she said there is little evidence that activation of the renin-angiotensin system is associated with disease progression, unlike in patients with reduced ejection fractions. “This may be why the trial was negative,” she speculated.

She also observed that patients in I-PRESERVE were largely similar to those in observational studies, but that they had fairly normal hemoglobin levels and renal function, “which is uncommon in the elderly with heart failure,” she pointed out. “Few had concentric hypertrophy, though some had concentric remodeling, and very few had advanced diastolic dysfunction or high filling pressures. So, this was a relatively healthy cohort and not as reflective of this syndrome as we would have hoped.”

The study was funded by Bristol-Myers Squibb Co. and Sanofi-Aventis. The results were simultaneously published online in the New England Journal of Medicine (doi:10.1056/NEJMoa08005450).

NEW ORLEANS — Heart failure patients with preserved systolic function did not benefit from treatment with an angiotensin II receptor blocker, according to results of the I-PRESERVE trial, the world's largest placebo-controlled trial of an ARB.

“Disappointingly, for this large group of patients—almost half the patients with heart failure—there remains no specific evidence-based therapy,” concluded Dr. Barry M. Massie, who presented the results of the Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) trial at the annual scientific sessions of the American Heart Association.

Although no pharmacologic therapy has been shown to be effective in improving outcomes in this type of heart failure, inhibitors of the renin-angiotensin-aldosterone system have been of interest because that system is involved in many of the processes associated with this syndrome, such as hypertension, left ventricular hypertrophy, myocardial fibrosis, and vascular dysfunction. Previous studies have hinted at benefits from ARBs and from ACE inhibitors, but statistically significant improvements have not been established, said Dr. Massie, professor of medicine at the University of California, San Francisco and chief of cardiology at the San Francisco Veterans Affairs Medical Center.

I-PRESERVE included 4,128 patients with class II-IV heart failure and a left ventricular ejection fraction of at least 45%. The population was similar to that seen in prior epidemiologic studies in several important ways. The patients were mostly women, were elderly (median age 72 years), and about 9 of 10 had a history of hypertension. The average left ventricular ejection fraction was 59%.

Patients were randomized to either irbesartan up to 300 mg daily or usual care (placebo). The primary end point was a composite of all-cause death, hospitalization for heart failure, myocardial infarction, unstable angina, arrhythmia, and stroke.

After a mean follow-up of approximately 4 years, the primary outcome rates were nearly identical, occurring in 36% (742 of 2,067) of the irbesartan patients and 37% (763 of 2,061) of the placebo group. Similarly, there were no significant differences in the major secondary end points of cardiovascular death and death or hospitalization due to heart failure, or in any of the eight prespecified subgroups, Dr. Massie reported.

“Irbesartan was unsuccessful in achieving its primary or secondary outcomes,” Dr. Massie announced. The results are consistent with two previous trials in patients with heart failure and preserved ejection fraction that did not show a positive treatment effect with either candesartan or perindopril, he added.

Dr. Massie acknowledged that this was a “very well treated population,” with most patients receiving diuretics and many receiving other medications. “After randomization, there was an intensification of all these therapies,” he observed, explaining that this can confound outcomes.

“For this field to move forward, we need a better understanding of the mechanisms underlying this syndrome, and we need to find potential targets above and beyond those used for low ejection fraction patients. We need to do something. This affects more than 2 million individuals in the United States alone.”

Dr. Margaret M. Redfield, professor of medicine at the Mayo Clinic, Rochester, Minn., called I-PRESERVE, “a very important trial, if only for the fact that ARBs and ACE inhibitors are already widely used for the treatment of heart failure with preserved ejection fraction, even though no randomized trial has shown a benefit. Two huge registries have shown that 60% are treated with these agents despite the lack of evidence.”

In this form of heart failure, she said there is little evidence that activation of the renin-angiotensin system is associated with disease progression, unlike in patients with reduced ejection fractions. “This may be why the trial was negative,” she speculated.

She also observed that patients in I-PRESERVE were largely similar to those in observational studies, but that they had fairly normal hemoglobin levels and renal function, “which is uncommon in the elderly with heart failure,” she pointed out. “Few had concentric hypertrophy, though some had concentric remodeling, and very few had advanced diastolic dysfunction or high filling pressures. So, this was a relatively healthy cohort and not as reflective of this syndrome as we would have hoped.”

The study was funded by Bristol-Myers Squibb Co. and Sanofi-Aventis. The results were simultaneously published online in the New England Journal of Medicine (doi:10.1056/NEJMoa08005450).

NEW ORLEANS — Heart failure patients with preserved systolic function did not benefit from treatment with an angiotensin II receptor blocker, according to results of the I-PRESERVE trial, the world's largest placebo-controlled trial of an ARB.

“Disappointingly, for this large group of patients—almost half the patients with heart failure—there remains no specific evidence-based therapy,” concluded Dr. Barry M. Massie, who presented the results of the Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) trial at the annual scientific sessions of the American Heart Association.

Although no pharmacologic therapy has been shown to be effective in improving outcomes in this type of heart failure, inhibitors of the renin-angiotensin-aldosterone system have been of interest because that system is involved in many of the processes associated with this syndrome, such as hypertension, left ventricular hypertrophy, myocardial fibrosis, and vascular dysfunction. Previous studies have hinted at benefits from ARBs and from ACE inhibitors, but statistically significant improvements have not been established, said Dr. Massie, professor of medicine at the University of California, San Francisco and chief of cardiology at the San Francisco Veterans Affairs Medical Center.

I-PRESERVE included 4,128 patients with class II-IV heart failure and a left ventricular ejection fraction of at least 45%. The population was similar to that seen in prior epidemiologic studies in several important ways. The patients were mostly women, were elderly (median age 72 years), and about 9 of 10 had a history of hypertension. The average left ventricular ejection fraction was 59%.

Patients were randomized to either irbesartan up to 300 mg daily or usual care (placebo). The primary end point was a composite of all-cause death, hospitalization for heart failure, myocardial infarction, unstable angina, arrhythmia, and stroke.

After a mean follow-up of approximately 4 years, the primary outcome rates were nearly identical, occurring in 36% (742 of 2,067) of the irbesartan patients and 37% (763 of 2,061) of the placebo group. Similarly, there were no significant differences in the major secondary end points of cardiovascular death and death or hospitalization due to heart failure, or in any of the eight prespecified subgroups, Dr. Massie reported.

“Irbesartan was unsuccessful in achieving its primary or secondary outcomes,” Dr. Massie announced. The results are consistent with two previous trials in patients with heart failure and preserved ejection fraction that did not show a positive treatment effect with either candesartan or perindopril, he added.

Dr. Massie acknowledged that this was a “very well treated population,” with most patients receiving diuretics and many receiving other medications. “After randomization, there was an intensification of all these therapies,” he observed, explaining that this can confound outcomes.

“For this field to move forward, we need a better understanding of the mechanisms underlying this syndrome, and we need to find potential targets above and beyond those used for low ejection fraction patients. We need to do something. This affects more than 2 million individuals in the United States alone.”

Dr. Margaret M. Redfield, professor of medicine at the Mayo Clinic, Rochester, Minn., called I-PRESERVE, “a very important trial, if only for the fact that ARBs and ACE inhibitors are already widely used for the treatment of heart failure with preserved ejection fraction, even though no randomized trial has shown a benefit. Two huge registries have shown that 60% are treated with these agents despite the lack of evidence.”

In this form of heart failure, she said there is little evidence that activation of the renin-angiotensin system is associated with disease progression, unlike in patients with reduced ejection fractions. “This may be why the trial was negative,” she speculated.

She also observed that patients in I-PRESERVE were largely similar to those in observational studies, but that they had fairly normal hemoglobin levels and renal function, “which is uncommon in the elderly with heart failure,” she pointed out. “Few had concentric hypertrophy, though some had concentric remodeling, and very few had advanced diastolic dysfunction or high filling pressures. So, this was a relatively healthy cohort and not as reflective of this syndrome as we would have hoped.”

The study was funded by Bristol-Myers Squibb Co. and Sanofi-Aventis. The results were simultaneously published online in the New England Journal of Medicine (doi:10.1056/NEJMoa08005450).

MUNICH — Metformin-treated diabetic patients with heart failure had strikingly lower morbidity and mortality than did those on oral sulfonylureas, in a long-term observational study.

“Our data suggest metformin is probably safe—and potentially effective—in congestive heart failure patients compared to treatment with sulfonylureas alone,” Dr. Chim C. Lang reported at the annual congress of the European Society of Cardiology.

The safety issue is key. Heart failure has long been considered a relative contraindication to metformin because of a supposedly increased risk of drug-related, potentially fatal, lactic acidosis. The concern has its origins in problems with phenformin, another insulin-sensitizing biguanide. But several lines of evidence suggest the concern over metformin has little or no merit, said Dr. Lang of Ninewells Hospital and Medical School, Dundee, Scotland.

How best to manage diabetes in patients with heart failure is a pressing issue, particularly in light of recent problems with the use of thiazolidinediones in this setting. Metformin could be a cheaper and safer alternative in this extremely common clinical situation. The incidence of heart failure in type 2 diabetic patients is 30.9 cases per 1,000 person-years, Dr. Lang noted.

He reported on all 774 type 2 diabetic patients who developed new-onset chronic heart failure in Tayside, Scotland, during 1994–2003. Ninety were managed with metformin monotherapy, 381 with sulfonylurea monotherapy, and 303 with both.

At 10 years of follow-up, 60% of patients in the metformin group were dead, compared with 77% who received sulfonyl-ureas alone and 66% with combination therapy.

Patients managed with sulfonylureas alone tended to be older, to be sicker, and to have worse renal function, and were less likely to be on β-blockers and aspirin, so those differences were adjusted for in a Cox regression analysis. The result: an adjusted 28% relative risk reduction in mortality with metformin alone.

The mortality curves diverged within the first year of follow-up. At 1 year, 90% of patients in the metformin group remained alive. They had an adjusted 55% relative risk reduction in 1-year mortality compared with the sulfonylurea-only group, while patients on both forms of therapy had a 34% relative risk reduction.

The combined risk of death or all-cause hospitalization was reduced by 26% in the metformin group compared with those on sulfonylureas alone. However, there was no significant difference between the sulfonylurea-only and combination therapy groups in the combined end point.

In an interview, Dr. Lang noted that he is conducting an ongoing, double-blind, placebo-controlled, randomized trial assessing whether 4 months of metformin improves exercise capacity, flow-mediated dilatation, and muscle enzyme activity in insulin-resistant patients with heart failure. It's a highly practical question, as poor exercise tolerance is one of the most debilitating aspects of heart failure.

The notion that metformin is safe in the setting of heart failure received a boost from a recent systematic review by investigators at the University of Alberta, Edmonton. They concluded, “Of the current antidiabetic agents, metformin is the only one not associated with any measurable harm in people with diabetes and heart failure and is associated with reduced mortality” (BMJ 2007;335:497).

In addition, the most recent Cochrane review concluded there were no cases of fatal or nonfatal lactic acidosis in 274 studies involving nearly 60,000 patient-years of metformin use (Cochrane Database Syst. Rev. Jan. 25, 2006 [epub doi:10.1002/14651858.CD002967.pub2

The observational Tayside study was funded by the British Heart Foundation. Dr. Lang's ongoing randomized trial is sponsored by the University of Dundee.

MUNICH — Metformin-treated diabetic patients with heart failure had strikingly lower morbidity and mortality than did those on oral sulfonylureas, in a long-term observational study.

“Our data suggest metformin is probably safe—and potentially effective—in congestive heart failure patients compared to treatment with sulfonylureas alone,” Dr. Chim C. Lang reported at the annual congress of the European Society of Cardiology.

The safety issue is key. Heart failure has long been considered a relative contraindication to metformin because of a supposedly increased risk of drug-related, potentially fatal, lactic acidosis. The concern has its origins in problems with phenformin, another insulin-sensitizing biguanide. But several lines of evidence suggest the concern over metformin has little or no merit, said Dr. Lang of Ninewells Hospital and Medical School, Dundee, Scotland.

How best to manage diabetes in patients with heart failure is a pressing issue, particularly in light of recent problems with the use of thiazolidinediones in this setting. Metformin could be a cheaper and safer alternative in this extremely common clinical situation. The incidence of heart failure in type 2 diabetic patients is 30.9 cases per 1,000 person-years, Dr. Lang noted.

He reported on all 774 type 2 diabetic patients who developed new-onset chronic heart failure in Tayside, Scotland, during 1994–2003. Ninety were managed with metformin monotherapy, 381 with sulfonylurea monotherapy, and 303 with both.

At 10 years of follow-up, 60% of patients in the metformin group were dead, compared with 77% who received sulfonyl-ureas alone and 66% with combination therapy.

Patients managed with sulfonylureas alone tended to be older, to be sicker, and to have worse renal function, and were less likely to be on β-blockers and aspirin, so those differences were adjusted for in a Cox regression analysis. The result: an adjusted 28% relative risk reduction in mortality with metformin alone.

The mortality curves diverged within the first year of follow-up. At 1 year, 90% of patients in the metformin group remained alive. They had an adjusted 55% relative risk reduction in 1-year mortality compared with the sulfonylurea-only group, while patients on both forms of therapy had a 34% relative risk reduction.

The combined risk of death or all-cause hospitalization was reduced by 26% in the metformin group compared with those on sulfonylureas alone. However, there was no significant difference between the sulfonylurea-only and combination therapy groups in the combined end point.

In an interview, Dr. Lang noted that he is conducting an ongoing, double-blind, placebo-controlled, randomized trial assessing whether 4 months of metformin improves exercise capacity, flow-mediated dilatation, and muscle enzyme activity in insulin-resistant patients with heart failure. It's a highly practical question, as poor exercise tolerance is one of the most debilitating aspects of heart failure.

The notion that metformin is safe in the setting of heart failure received a boost from a recent systematic review by investigators at the University of Alberta, Edmonton. They concluded, “Of the current antidiabetic agents, metformin is the only one not associated with any measurable harm in people with diabetes and heart failure and is associated with reduced mortality” (BMJ 2007;335:497).

In addition, the most recent Cochrane review concluded there were no cases of fatal or nonfatal lactic acidosis in 274 studies involving nearly 60,000 patient-years of metformin use (Cochrane Database Syst. Rev. Jan. 25, 2006 [epub doi:10.1002/14651858.CD002967.pub2

The observational Tayside study was funded by the British Heart Foundation. Dr. Lang's ongoing randomized trial is sponsored by the University of Dundee.

MUNICH — Metformin-treated diabetic patients with heart failure had strikingly lower morbidity and mortality than did those on oral sulfonylureas, in a long-term observational study.

“Our data suggest metformin is probably safe—and potentially effective—in congestive heart failure patients compared to treatment with sulfonylureas alone,” Dr. Chim C. Lang reported at the annual congress of the European Society of Cardiology.

The safety issue is key. Heart failure has long been considered a relative contraindication to metformin because of a supposedly increased risk of drug-related, potentially fatal, lactic acidosis. The concern has its origins in problems with phenformin, another insulin-sensitizing biguanide. But several lines of evidence suggest the concern over metformin has little or no merit, said Dr. Lang of Ninewells Hospital and Medical School, Dundee, Scotland.

How best to manage diabetes in patients with heart failure is a pressing issue, particularly in light of recent problems with the use of thiazolidinediones in this setting. Metformin could be a cheaper and safer alternative in this extremely common clinical situation. The incidence of heart failure in type 2 diabetic patients is 30.9 cases per 1,000 person-years, Dr. Lang noted.

He reported on all 774 type 2 diabetic patients who developed new-onset chronic heart failure in Tayside, Scotland, during 1994–2003. Ninety were managed with metformin monotherapy, 381 with sulfonylurea monotherapy, and 303 with both.

At 10 years of follow-up, 60% of patients in the metformin group were dead, compared with 77% who received sulfonyl-ureas alone and 66% with combination therapy.

Patients managed with sulfonylureas alone tended to be older, to be sicker, and to have worse renal function, and were less likely to be on β-blockers and aspirin, so those differences were adjusted for in a Cox regression analysis. The result: an adjusted 28% relative risk reduction in mortality with metformin alone.

The mortality curves diverged within the first year of follow-up. At 1 year, 90% of patients in the metformin group remained alive. They had an adjusted 55% relative risk reduction in 1-year mortality compared with the sulfonylurea-only group, while patients on both forms of therapy had a 34% relative risk reduction.

The combined risk of death or all-cause hospitalization was reduced by 26% in the metformin group compared with those on sulfonylureas alone. However, there was no significant difference between the sulfonylurea-only and combination therapy groups in the combined end point.

In an interview, Dr. Lang noted that he is conducting an ongoing, double-blind, placebo-controlled, randomized trial assessing whether 4 months of metformin improves exercise capacity, flow-mediated dilatation, and muscle enzyme activity in insulin-resistant patients with heart failure. It's a highly practical question, as poor exercise tolerance is one of the most debilitating aspects of heart failure.

The notion that metformin is safe in the setting of heart failure received a boost from a recent systematic review by investigators at the University of Alberta, Edmonton. They concluded, “Of the current antidiabetic agents, metformin is the only one not associated with any measurable harm in people with diabetes and heart failure and is associated with reduced mortality” (BMJ 2007;335:497).

In addition, the most recent Cochrane review concluded there were no cases of fatal or nonfatal lactic acidosis in 274 studies involving nearly 60,000 patient-years of metformin use (Cochrane Database Syst. Rev. Jan. 25, 2006 [epub doi:10.1002/14651858.CD002967.pub2

The observational Tayside study was funded by the British Heart Foundation. Dr. Lang's ongoing randomized trial is sponsored by the University of Dundee.

TORONTO — The rate at which eligible, appropriate patients with a low left ventricular ejection fraction miss out on getting an implantable cardioverter defibrillator might be lower than most people think.

After ineligible patients and those who refused the device were accounted for, the “true miss” rate, or rate of patients with ejection fractions of 35% or less who failed to get an ICD was 7% in a random sample of 228 patients who underwent echocardiography scanning during 2005–2007 at Jefferson Medical College, Philadelphia.

However, the ICD implant rate in large, observational studies has usually been reported as about 25%–40% in patients with ejection fractions of 35% or less, Dr. Shaw Natan said while presenting a poster at the 14th World Congress on Heart Disease.

At Jefferson, the implant rate in the 228 patients who were the focus of this study was 42%, suggesting a miss rate of 68%. But assessing each patient individually showed that in most cases there was a good reason for the omission,” said Dr. Natan, a cardiologist formerly at Jefferson and now at St. Elizabeth's Medical Center in Boston, in an interview.

The 228 patients in the sample had an average age of 66 (range 29–96), and 68% were men. Their average LVEF was 21%.

Among the 132 patients in the sample who did not get an ICD, 89 (39% of the total) were ineligible: 34 had an inadequate trial of medical treatment or revascularization, 19 died, 17 had a life expectancy of less than 1 year or dementia, 10 were lost to follow-up, and 9 had other reasons.

Of the remaining 43 patients who were eligible for an ICD, 27 declined the device when it was offered. This left 16 patients (7% of the total number of patients evaluated) who were true misses for an ICD: They had no contraindications and were willing to receive treatment.

TORONTO — The rate at which eligible, appropriate patients with a low left ventricular ejection fraction miss out on getting an implantable cardioverter defibrillator might be lower than most people think.

After ineligible patients and those who refused the device were accounted for, the “true miss” rate, or rate of patients with ejection fractions of 35% or less who failed to get an ICD was 7% in a random sample of 228 patients who underwent echocardiography scanning during 2005–2007 at Jefferson Medical College, Philadelphia.

However, the ICD implant rate in large, observational studies has usually been reported as about 25%–40% in patients with ejection fractions of 35% or less, Dr. Shaw Natan said while presenting a poster at the 14th World Congress on Heart Disease.

At Jefferson, the implant rate in the 228 patients who were the focus of this study was 42%, suggesting a miss rate of 68%. But assessing each patient individually showed that in most cases there was a good reason for the omission,” said Dr. Natan, a cardiologist formerly at Jefferson and now at St. Elizabeth's Medical Center in Boston, in an interview.

The 228 patients in the sample had an average age of 66 (range 29–96), and 68% were men. Their average LVEF was 21%.

Among the 132 patients in the sample who did not get an ICD, 89 (39% of the total) were ineligible: 34 had an inadequate trial of medical treatment or revascularization, 19 died, 17 had a life expectancy of less than 1 year or dementia, 10 were lost to follow-up, and 9 had other reasons.

Of the remaining 43 patients who were eligible for an ICD, 27 declined the device when it was offered. This left 16 patients (7% of the total number of patients evaluated) who were true misses for an ICD: They had no contraindications and were willing to receive treatment.

TORONTO — The rate at which eligible, appropriate patients with a low left ventricular ejection fraction miss out on getting an implantable cardioverter defibrillator might be lower than most people think.

After ineligible patients and those who refused the device were accounted for, the “true miss” rate, or rate of patients with ejection fractions of 35% or less who failed to get an ICD was 7% in a random sample of 228 patients who underwent echocardiography scanning during 2005–2007 at Jefferson Medical College, Philadelphia.

However, the ICD implant rate in large, observational studies has usually been reported as about 25%–40% in patients with ejection fractions of 35% or less, Dr. Shaw Natan said while presenting a poster at the 14th World Congress on Heart Disease.

At Jefferson, the implant rate in the 228 patients who were the focus of this study was 42%, suggesting a miss rate of 68%. But assessing each patient individually showed that in most cases there was a good reason for the omission,” said Dr. Natan, a cardiologist formerly at Jefferson and now at St. Elizabeth's Medical Center in Boston, in an interview.

The 228 patients in the sample had an average age of 66 (range 29–96), and 68% were men. Their average LVEF was 21%.

Among the 132 patients in the sample who did not get an ICD, 89 (39% of the total) were ineligible: 34 had an inadequate trial of medical treatment or revascularization, 19 died, 17 had a life expectancy of less than 1 year or dementia, 10 were lost to follow-up, and 9 had other reasons.

Of the remaining 43 patients who were eligible for an ICD, 27 declined the device when it was offered. This left 16 patients (7% of the total number of patients evaluated) who were true misses for an ICD: They had no contraindications and were willing to receive treatment.

TORONTO — In patients with mild heart failure, cardiac resynchronization therapy improved composite clinical response scores at 18 months, was associated with left ventricular reverse remodeling, reduced the risk of heart failure hospitalization, and lowered the combined risk of morbidity and mortality, compared with optimal medical therapy.

The 18-month data from the European cohort of the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial supported secondary conclusions from the previously reported 12-month analysis, which, although it indicated that the trial missed its primary clinical composite end point, showed evidence of remodeling and clinical benefit with CRT in mild heart failure (HF).

“Ongoing CRT trials in New York Heart Association class I and II patients may confirm these observations and expand the indication for CRT to this population of heart failure patients,” said Dr. William T. Abraham, who presented the data at the annual meeting of the Heart Failure Society of America.

The REVERSE trial was a multinational prospective effort involving 610 patients with mild or asymptomatic HF and ventricular dyssynchrony. All patients received a CRT device in addition to optimal medical therapy; 191 were randomized to have the device turned on and 419 were randomized to have it turned off.

Eligible patients had left ventricular ejection fractions below 40%, had QRS durations of at least 120 milliseconds, and were already on optimal medical therapy.

The study's main results were published online in the Journal of the American College of Cardiology in September (doi:10.1016/j.jacc.2008.08.027

At this meeting, Dr. Abraham presented the 18-month results from 262 patients in the European cohort, for whom follow-up is continuing to 24 months. These patients, he noted, differed significantly from the North American cohort in their baseline characteristics: They were younger, less likely to have ischemic cardiomyopathy, and less likely to have an implantable cardioverter defibrillator. The European patients had similar ejection fractions to the North American cohort, but had a bit more left ventricular enlargement and slightly longer QRS durations.

In this study population the primary end point significantly favored CRT therapy at 18 months, reported Dr. Abraham, director of the division of cardiovascular medicine at the Ohio State University, Columbus. The proportion of patients who had worsened at 18 months was 29% in the control group vs. 15% in the CRT group, a highly significant difference.

LVESVI improvements seen at 12 months were sustained at 18 months. Also, left ventricular end-diastolic volume index and ejection fraction were both improved in CRT patients, compared with controls.

Furthermore, all-cause mortality did not differ between treatments, while a “remarkable” 58% reduction was seen in the risk of HF hospitalization in the CRT group at 18 months. The absolute rates of hospitalization at 18 months were 13.5% in the control arm and 5.5% in the CRT arm. The combined risk of first HF hospitalization and death was reduced 50% with CRT. Rates of non-HF hospitalization were identical in the CRT on and off groups.

These results “show that there is a favorable impact on remodeling that continues beyond 12 months and that there is a favorable impact on heart failure outcomes … and no signal of an adverse effect on mortality,” commented Dr. William G. Stevenson of Brigham and Women's Hospital in Boston.

REVERSE was sponsored by Medtronic Inc. Dr. Abraham reports research grants, speaker honoraria, and consulting fees from Medtronic, St. Jude Medical Inc., and Biotronik GmbH.

TORONTO — In patients with mild heart failure, cardiac resynchronization therapy improved composite clinical response scores at 18 months, was associated with left ventricular reverse remodeling, reduced the risk of heart failure hospitalization, and lowered the combined risk of morbidity and mortality, compared with optimal medical therapy.

The 18-month data from the European cohort of the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial supported secondary conclusions from the previously reported 12-month analysis, which, although it indicated that the trial missed its primary clinical composite end point, showed evidence of remodeling and clinical benefit with CRT in mild heart failure (HF).

“Ongoing CRT trials in New York Heart Association class I and II patients may confirm these observations and expand the indication for CRT to this population of heart failure patients,” said Dr. William T. Abraham, who presented the data at the annual meeting of the Heart Failure Society of America.

The REVERSE trial was a multinational prospective effort involving 610 patients with mild or asymptomatic HF and ventricular dyssynchrony. All patients received a CRT device in addition to optimal medical therapy; 191 were randomized to have the device turned on and 419 were randomized to have it turned off.

Eligible patients had left ventricular ejection fractions below 40%, had QRS durations of at least 120 milliseconds, and were already on optimal medical therapy.

The study's main results were published online in the Journal of the American College of Cardiology in September (doi:10.1016/j.jacc.2008.08.027

At this meeting, Dr. Abraham presented the 18-month results from 262 patients in the European cohort, for whom follow-up is continuing to 24 months. These patients, he noted, differed significantly from the North American cohort in their baseline characteristics: They were younger, less likely to have ischemic cardiomyopathy, and less likely to have an implantable cardioverter defibrillator. The European patients had similar ejection fractions to the North American cohort, but had a bit more left ventricular enlargement and slightly longer QRS durations.

In this study population the primary end point significantly favored CRT therapy at 18 months, reported Dr. Abraham, director of the division of cardiovascular medicine at the Ohio State University, Columbus. The proportion of patients who had worsened at 18 months was 29% in the control group vs. 15% in the CRT group, a highly significant difference.

LVESVI improvements seen at 12 months were sustained at 18 months. Also, left ventricular end-diastolic volume index and ejection fraction were both improved in CRT patients, compared with controls.

Furthermore, all-cause mortality did not differ between treatments, while a “remarkable” 58% reduction was seen in the risk of HF hospitalization in the CRT group at 18 months. The absolute rates of hospitalization at 18 months were 13.5% in the control arm and 5.5% in the CRT arm. The combined risk of first HF hospitalization and death was reduced 50% with CRT. Rates of non-HF hospitalization were identical in the CRT on and off groups.

These results “show that there is a favorable impact on remodeling that continues beyond 12 months and that there is a favorable impact on heart failure outcomes … and no signal of an adverse effect on mortality,” commented Dr. William G. Stevenson of Brigham and Women's Hospital in Boston.

REVERSE was sponsored by Medtronic Inc. Dr. Abraham reports research grants, speaker honoraria, and consulting fees from Medtronic, St. Jude Medical Inc., and Biotronik GmbH.

TORONTO — In patients with mild heart failure, cardiac resynchronization therapy improved composite clinical response scores at 18 months, was associated with left ventricular reverse remodeling, reduced the risk of heart failure hospitalization, and lowered the combined risk of morbidity and mortality, compared with optimal medical therapy.

The 18-month data from the European cohort of the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial supported secondary conclusions from the previously reported 12-month analysis, which, although it indicated that the trial missed its primary clinical composite end point, showed evidence of remodeling and clinical benefit with CRT in mild heart failure (HF).

“Ongoing CRT trials in New York Heart Association class I and II patients may confirm these observations and expand the indication for CRT to this population of heart failure patients,” said Dr. William T. Abraham, who presented the data at the annual meeting of the Heart Failure Society of America.

The REVERSE trial was a multinational prospective effort involving 610 patients with mild or asymptomatic HF and ventricular dyssynchrony. All patients received a CRT device in addition to optimal medical therapy; 191 were randomized to have the device turned on and 419 were randomized to have it turned off.

Eligible patients had left ventricular ejection fractions below 40%, had QRS durations of at least 120 milliseconds, and were already on optimal medical therapy.

The study's main results were published online in the Journal of the American College of Cardiology in September (doi:10.1016/j.jacc.2008.08.027

At this meeting, Dr. Abraham presented the 18-month results from 262 patients in the European cohort, for whom follow-up is continuing to 24 months. These patients, he noted, differed significantly from the North American cohort in their baseline characteristics: They were younger, less likely to have ischemic cardiomyopathy, and less likely to have an implantable cardioverter defibrillator. The European patients had similar ejection fractions to the North American cohort, but had a bit more left ventricular enlargement and slightly longer QRS durations.

In this study population the primary end point significantly favored CRT therapy at 18 months, reported Dr. Abraham, director of the division of cardiovascular medicine at the Ohio State University, Columbus. The proportion of patients who had worsened at 18 months was 29% in the control group vs. 15% in the CRT group, a highly significant difference.

LVESVI improvements seen at 12 months were sustained at 18 months. Also, left ventricular end-diastolic volume index and ejection fraction were both improved in CRT patients, compared with controls.

Furthermore, all-cause mortality did not differ between treatments, while a “remarkable” 58% reduction was seen in the risk of HF hospitalization in the CRT group at 18 months. The absolute rates of hospitalization at 18 months were 13.5% in the control arm and 5.5% in the CRT arm. The combined risk of first HF hospitalization and death was reduced 50% with CRT. Rates of non-HF hospitalization were identical in the CRT on and off groups.

These results “show that there is a favorable impact on remodeling that continues beyond 12 months and that there is a favorable impact on heart failure outcomes … and no signal of an adverse effect on mortality,” commented Dr. William G. Stevenson of Brigham and Women's Hospital in Boston.

REVERSE was sponsored by Medtronic Inc. Dr. Abraham reports research grants, speaker honoraria, and consulting fees from Medtronic, St. Jude Medical Inc., and Biotronik GmbH.

CHICAGO — Deep vein thrombosis prophylaxis for hospitalized patients with heart failure is recommended in evidence-based guidelines but is often omitted in practice.

“High medical acuity, an increased prevalence of venous thromboembolism [VTE] risk factors, and a low rate of VTE prophylaxis present a triple threat to heart failure patients,” Dr. Gregory Piazza said at the annual meeting of the American College of Cardiology.

He studied 5,451 consecutive patients with ultrasound-confirmed deep vein thrombosis (DVT) in a prospective registry that included 685 patients with a history of heart failure. The heart failure patients were significantly more likely to have VTE risk factors, including acute infection, chronic obstructive pulmonary disease, and immobilization, and they had more comorbid medical conditions (see table). Moreover, 48% of the heart failure patients had been hospitalized recently. Yet only 46% of them had received any VTE prophylaxis, despite the published recommendations of the American College of Chest Physicians and other groups.

“I think heart failure patients find themselves in a catch-22, where all of the comorbid conditions that give them such high medical acuity and put them at such high risk for VTE also put them at high risk for bleeding. So there's a tendency to shy away from pharmacologic prophylaxis with anticoagulants in these patients,” said Dr. Piazza, a cardiovascular medicine fellow at Beth Israel Deaconess Medical Center, Boston. “Also, I think that because heart failure patients have so many comorbid conditions, VTE prophylaxis might fall lower on the priority list of things physicians have to take care of when they're managing these patients.”

Bringing about improvement in the situation will entail making clinicians more aware of the ACCP guidelines recommending VTE prophylaxis. In addition, cardiologists who consult on heart failure patients need to identify VTE prophylaxis on their list of recommendations.

In an interview, Dr. Piazza said future studies will establish whether it's safe and effective for hospitalized heart failure patients to continue on VTE prophylaxis after being discharged home, as is now routine for 4–6 weeks in orthopedic surgery patients.

This issue of VTE prophylaxis in heart failure patients is not going to go away, the physician stressed. “Some studies show VTE risk increases as left ventricular ejection fraction declines, perhaps suggesting that our very advanced heart failure patients are at even higher risk. And as our treatments for coronary disease and heart failure continue to improve, we're going to have many more patients hanging out in the lower ejection fraction ranges,” Dr. Piazza noted.

This study was sponsored by Sanofi Aventis. Dr. Piazza disclosed he has no financial ties with the company.

The catch-22 is, the conditions that increase heart failure patients' VTE risk also increase their bleeding risk. DR. PIAZZA

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Deep vein thrombosis prophylaxis for hospitalized patients with heart failure is recommended in evidence-based guidelines but is often omitted in practice.

“High medical acuity, an increased prevalence of venous thromboembolism [VTE] risk factors, and a low rate of VTE prophylaxis present a triple threat to heart failure patients,” Dr. Gregory Piazza said at the annual meeting of the American College of Cardiology.

He studied 5,451 consecutive patients with ultrasound-confirmed deep vein thrombosis (DVT) in a prospective registry that included 685 patients with a history of heart failure. The heart failure patients were significantly more likely to have VTE risk factors, including acute infection, chronic obstructive pulmonary disease, and immobilization, and they had more comorbid medical conditions (see table). Moreover, 48% of the heart failure patients had been hospitalized recently. Yet only 46% of them had received any VTE prophylaxis, despite the published recommendations of the American College of Chest Physicians and other groups.

“I think heart failure patients find themselves in a catch-22, where all of the comorbid conditions that give them such high medical acuity and put them at such high risk for VTE also put them at high risk for bleeding. So there's a tendency to shy away from pharmacologic prophylaxis with anticoagulants in these patients,” said Dr. Piazza, a cardiovascular medicine fellow at Beth Israel Deaconess Medical Center, Boston. “Also, I think that because heart failure patients have so many comorbid conditions, VTE prophylaxis might fall lower on the priority list of things physicians have to take care of when they're managing these patients.”

Bringing about improvement in the situation will entail making clinicians more aware of the ACCP guidelines recommending VTE prophylaxis. In addition, cardiologists who consult on heart failure patients need to identify VTE prophylaxis on their list of recommendations.

In an interview, Dr. Piazza said future studies will establish whether it's safe and effective for hospitalized heart failure patients to continue on VTE prophylaxis after being discharged home, as is now routine for 4–6 weeks in orthopedic surgery patients.

This issue of VTE prophylaxis in heart failure patients is not going to go away, the physician stressed. “Some studies show VTE risk increases as left ventricular ejection fraction declines, perhaps suggesting that our very advanced heart failure patients are at even higher risk. And as our treatments for coronary disease and heart failure continue to improve, we're going to have many more patients hanging out in the lower ejection fraction ranges,” Dr. Piazza noted.

This study was sponsored by Sanofi Aventis. Dr. Piazza disclosed he has no financial ties with the company.

The catch-22 is, the conditions that increase heart failure patients' VTE risk also increase their bleeding risk. DR. PIAZZA

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Deep vein thrombosis prophylaxis for hospitalized patients with heart failure is recommended in evidence-based guidelines but is often omitted in practice.

“High medical acuity, an increased prevalence of venous thromboembolism [VTE] risk factors, and a low rate of VTE prophylaxis present a triple threat to heart failure patients,” Dr. Gregory Piazza said at the annual meeting of the American College of Cardiology.

He studied 5,451 consecutive patients with ultrasound-confirmed deep vein thrombosis (DVT) in a prospective registry that included 685 patients with a history of heart failure. The heart failure patients were significantly more likely to have VTE risk factors, including acute infection, chronic obstructive pulmonary disease, and immobilization, and they had more comorbid medical conditions (see table). Moreover, 48% of the heart failure patients had been hospitalized recently. Yet only 46% of them had received any VTE prophylaxis, despite the published recommendations of the American College of Chest Physicians and other groups.

“I think heart failure patients find themselves in a catch-22, where all of the comorbid conditions that give them such high medical acuity and put them at such high risk for VTE also put them at high risk for bleeding. So there's a tendency to shy away from pharmacologic prophylaxis with anticoagulants in these patients,” said Dr. Piazza, a cardiovascular medicine fellow at Beth Israel Deaconess Medical Center, Boston. “Also, I think that because heart failure patients have so many comorbid conditions, VTE prophylaxis might fall lower on the priority list of things physicians have to take care of when they're managing these patients.”

Bringing about improvement in the situation will entail making clinicians more aware of the ACCP guidelines recommending VTE prophylaxis. In addition, cardiologists who consult on heart failure patients need to identify VTE prophylaxis on their list of recommendations.

In an interview, Dr. Piazza said future studies will establish whether it's safe and effective for hospitalized heart failure patients to continue on VTE prophylaxis after being discharged home, as is now routine for 4–6 weeks in orthopedic surgery patients.

This issue of VTE prophylaxis in heart failure patients is not going to go away, the physician stressed. “Some studies show VTE risk increases as left ventricular ejection fraction declines, perhaps suggesting that our very advanced heart failure patients are at even higher risk. And as our treatments for coronary disease and heart failure continue to improve, we're going to have many more patients hanging out in the lower ejection fraction ranges,” Dr. Piazza noted.

This study was sponsored by Sanofi Aventis. Dr. Piazza disclosed he has no financial ties with the company.

The catch-22 is, the conditions that increase heart failure patients' VTE risk also increase their bleeding risk. DR. PIAZZA

ELSEVIER GLOBAL MEDICAL NEWS

The inflammatory markers interleukin-6 and C-reactive protein as well as macroalbuminuria are independently predictive of heart failure, according to a study that followed nearly 7,000 Americans for a median of 4 years.

Each standard deviation increase in serum interleukin-6 or CRP level raised the risk of heart failure (HF) by 50% and 38%, respectively, while the presence of macroalbuminuria increased the risk 4.3-fold (J. Am. Coll. Cardiol. 2008;51:1775–83).

These associations were strong “even after adjustment for established risk factors, LV [left ventricular] dysfunction, and interim MI,” wrote Dr. Hossein Bahrami of Johns Hopkins University, Baltimore, and colleagues.

The community-based Multi-Ethnic Study of Atherosclerosis is a multicenter cohort study of 6,814 whites, blacks, Hispanics, and Chinese Americans with no history of symptomatic cardiovascular disease. Overall, 79 participants developed HF during the study period and 26 of those individuals (33%) had an interim MI. Participants who developed HF were more likely to be older, male, obese, and current smokers and to have hypertension and diabetes.

The presence of metabolic syndrome at baseline (seen in 35% of participants) more than doubled the risk of HF. Specifically, the absolute risk of HF in obese individuals was 16/1,000, compared with 10/1,000 in the nonobese. However, the association between obesity and incident HF was no longer significant after the model was adjusted to include the two inflammatory markers, they reported.

Very few participants (1.3%) had left ventricular ejection fraction (LVEF) below 50%, though 10% of participants had left ventricular hypertrophy (LVH) at baseline by Framingham criteria. Among the individuals who developed HF, rates of LVEF below 50% and LVH were 15% and 32%, respectively.

LVEF was the strongest predictor of incident HF and was therefore incorporated into the multivariate analysis. Among the 60 participants with LV function data at time of HF diagnosis, 87% had LVEF of 30% or greater, 65% had LVEF of 40% or greater, and 55% had LVEF of 50% or greater, the investigators wrote.

The inflammatory markers interleukin-6 and C-reactive protein as well as macroalbuminuria are independently predictive of heart failure, according to a study that followed nearly 7,000 Americans for a median of 4 years.

Each standard deviation increase in serum interleukin-6 or CRP level raised the risk of heart failure (HF) by 50% and 38%, respectively, while the presence of macroalbuminuria increased the risk 4.3-fold (J. Am. Coll. Cardiol. 2008;51:1775–83).

These associations were strong “even after adjustment for established risk factors, LV [left ventricular] dysfunction, and interim MI,” wrote Dr. Hossein Bahrami of Johns Hopkins University, Baltimore, and colleagues.

The community-based Multi-Ethnic Study of Atherosclerosis is a multicenter cohort study of 6,814 whites, blacks, Hispanics, and Chinese Americans with no history of symptomatic cardiovascular disease. Overall, 79 participants developed HF during the study period and 26 of those individuals (33%) had an interim MI. Participants who developed HF were more likely to be older, male, obese, and current smokers and to have hypertension and diabetes.

The presence of metabolic syndrome at baseline (seen in 35% of participants) more than doubled the risk of HF. Specifically, the absolute risk of HF in obese individuals was 16/1,000, compared with 10/1,000 in the nonobese. However, the association between obesity and incident HF was no longer significant after the model was adjusted to include the two inflammatory markers, they reported.

Very few participants (1.3%) had left ventricular ejection fraction (LVEF) below 50%, though 10% of participants had left ventricular hypertrophy (LVH) at baseline by Framingham criteria. Among the individuals who developed HF, rates of LVEF below 50% and LVH were 15% and 32%, respectively.

LVEF was the strongest predictor of incident HF and was therefore incorporated into the multivariate analysis. Among the 60 participants with LV function data at time of HF diagnosis, 87% had LVEF of 30% or greater, 65% had LVEF of 40% or greater, and 55% had LVEF of 50% or greater, the investigators wrote.

The inflammatory markers interleukin-6 and C-reactive protein as well as macroalbuminuria are independently predictive of heart failure, according to a study that followed nearly 7,000 Americans for a median of 4 years.

Each standard deviation increase in serum interleukin-6 or CRP level raised the risk of heart failure (HF) by 50% and 38%, respectively, while the presence of macroalbuminuria increased the risk 4.3-fold (J. Am. Coll. Cardiol. 2008;51:1775–83).

These associations were strong “even after adjustment for established risk factors, LV [left ventricular] dysfunction, and interim MI,” wrote Dr. Hossein Bahrami of Johns Hopkins University, Baltimore, and colleagues.

The community-based Multi-Ethnic Study of Atherosclerosis is a multicenter cohort study of 6,814 whites, blacks, Hispanics, and Chinese Americans with no history of symptomatic cardiovascular disease. Overall, 79 participants developed HF during the study period and 26 of those individuals (33%) had an interim MI. Participants who developed HF were more likely to be older, male, obese, and current smokers and to have hypertension and diabetes.

The presence of metabolic syndrome at baseline (seen in 35% of participants) more than doubled the risk of HF. Specifically, the absolute risk of HF in obese individuals was 16/1,000, compared with 10/1,000 in the nonobese. However, the association between obesity and incident HF was no longer significant after the model was adjusted to include the two inflammatory markers, they reported.

Very few participants (1.3%) had left ventricular ejection fraction (LVEF) below 50%, though 10% of participants had left ventricular hypertrophy (LVH) at baseline by Framingham criteria. Among the individuals who developed HF, rates of LVEF below 50% and LVH were 15% and 32%, respectively.

LVEF was the strongest predictor of incident HF and was therefore incorporated into the multivariate analysis. Among the 60 participants with LV function data at time of HF diagnosis, 87% had LVEF of 30% or greater, 65% had LVEF of 40% or greater, and 55% had LVEF of 50% or greater, the investigators wrote.

BOSTON — Patients with nonischemic cardiomyopathy who received an implantable cardioverter defibrillator did not have a survival benefit while listed as status 2 for a potential heart transplant, compared with patients who did not have an implantable defibrillator, based on records from more than 2,500 U.S. patients who were listed during 2000–2005.

In contrast, patients with ischemic cardiomyopathy who had an implantable cardioverter defibrillator (ICD) while listed as status 2 for a heart transplant during the same period had a significant 6% absolute survival advantage compared with patients without an ICD during the same period, Dr. Katherine Lietz reported at the annual meeting of the International Society for Heart and Lung Transplantation.

The reason for this difference in the impact of ICDs on survival based on whether a patient's cardiomyopathy had an ischemic or nonischemic etiology is not clear, she said. In addition, this finding should not be viewed as a reason to not place ICDs in patients with nonischemic cardiomyopathy, said Dr. Lietz, a transplant cardiologist at Columbia University in New York. Rather, the finding suggests that more research should be done to identify the determinants of survival in patients with nonischemic cardiomyopathy who are awaiting a heart transplant.

Her analysis focused on U.S. patients listed with the United Network for Organ Sharing as status 2 patients, defined as those who meet general criteria for a heart transplant, but are not “high urgency” status 1 patients.

During the period studied, use of ICDs in status 2 patients jumped more than twofold, rising from 37% in 2005 to 77% of listed status 2 patients in 2005, Dr. Lietz said. A total of 6,201 patients were listed as status 2 for a heart transplant in this period: 3,448 patients with ischemic-etiology cardiomyopathy and 2,753 patients with a nonischemic etiology. The vast majority (98%) of these patients who received an ICD had it implanted before they were listed for a heart transplant.

The 3-year survival rate of all patients with ischemic cardiomyopathy who had an ICD was 84%, compared with 76% among patients who did not receive an ICD. The researchers then ran the same analysis only on patients who remained on the list and did not receive a donated heart. In this subgroup, the 3-year survival rate with an ICD was 73.6%, and without an ICD it was 67.4%, a significant difference.

The 6.2% absolute improvement in survival over 3 years linked with ICD use was comparable with the survival benefit seen with ICD use in the Sudden Cardiac Death Heart Failure Trial (SCD-HFT), Dr. Lietz noted.

In contrast, among all patients with nonischemic cardiomyopathy who were listed as status 2, the 3-year survival rate with an ICD was 79.8%, compared with 81.2% among patients without an ICD, a “surprising” finding, said Dr. Lietz. This unexpected disparity remained among those who remained listed without a new heart. The survival rate was 65.7% with an ICD and 74.5% without an ICD, a difference that was not statistically significant, Dr. Lietz said.

Presence of an ICD did not affect the 3-year survival rate in status 2 patients with nonischemic cardiomyopathy. DR. LIETZ

BOSTON — Patients with nonischemic cardiomyopathy who received an implantable cardioverter defibrillator did not have a survival benefit while listed as status 2 for a potential heart transplant, compared with patients who did not have an implantable defibrillator, based on records from more than 2,500 U.S. patients who were listed during 2000–2005.

In contrast, patients with ischemic cardiomyopathy who had an implantable cardioverter defibrillator (ICD) while listed as status 2 for a heart transplant during the same period had a significant 6% absolute survival advantage compared with patients without an ICD during the same period, Dr. Katherine Lietz reported at the annual meeting of the International Society for Heart and Lung Transplantation.

The reason for this difference in the impact of ICDs on survival based on whether a patient's cardiomyopathy had an ischemic or nonischemic etiology is not clear, she said. In addition, this finding should not be viewed as a reason to not place ICDs in patients with nonischemic cardiomyopathy, said Dr. Lietz, a transplant cardiologist at Columbia University in New York. Rather, the finding suggests that more research should be done to identify the determinants of survival in patients with nonischemic cardiomyopathy who are awaiting a heart transplant.

Her analysis focused on U.S. patients listed with the United Network for Organ Sharing as status 2 patients, defined as those who meet general criteria for a heart transplant, but are not “high urgency” status 1 patients.

During the period studied, use of ICDs in status 2 patients jumped more than twofold, rising from 37% in 2005 to 77% of listed status 2 patients in 2005, Dr. Lietz said. A total of 6,201 patients were listed as status 2 for a heart transplant in this period: 3,448 patients with ischemic-etiology cardiomyopathy and 2,753 patients with a nonischemic etiology. The vast majority (98%) of these patients who received an ICD had it implanted before they were listed for a heart transplant.

The 3-year survival rate of all patients with ischemic cardiomyopathy who had an ICD was 84%, compared with 76% among patients who did not receive an ICD. The researchers then ran the same analysis only on patients who remained on the list and did not receive a donated heart. In this subgroup, the 3-year survival rate with an ICD was 73.6%, and without an ICD it was 67.4%, a significant difference.

The 6.2% absolute improvement in survival over 3 years linked with ICD use was comparable with the survival benefit seen with ICD use in the Sudden Cardiac Death Heart Failure Trial (SCD-HFT), Dr. Lietz noted.

In contrast, among all patients with nonischemic cardiomyopathy who were listed as status 2, the 3-year survival rate with an ICD was 79.8%, compared with 81.2% among patients without an ICD, a “surprising” finding, said Dr. Lietz. This unexpected disparity remained among those who remained listed without a new heart. The survival rate was 65.7% with an ICD and 74.5% without an ICD, a difference that was not statistically significant, Dr. Lietz said.

Presence of an ICD did not affect the 3-year survival rate in status 2 patients with nonischemic cardiomyopathy. DR. LIETZ

BOSTON — Patients with nonischemic cardiomyopathy who received an implantable cardioverter defibrillator did not have a survival benefit while listed as status 2 for a potential heart transplant, compared with patients who did not have an implantable defibrillator, based on records from more than 2,500 U.S. patients who were listed during 2000–2005.

In contrast, patients with ischemic cardiomyopathy who had an implantable cardioverter defibrillator (ICD) while listed as status 2 for a heart transplant during the same period had a significant 6% absolute survival advantage compared with patients without an ICD during the same period, Dr. Katherine Lietz reported at the annual meeting of the International Society for Heart and Lung Transplantation.

The reason for this difference in the impact of ICDs on survival based on whether a patient's cardiomyopathy had an ischemic or nonischemic etiology is not clear, she said. In addition, this finding should not be viewed as a reason to not place ICDs in patients with nonischemic cardiomyopathy, said Dr. Lietz, a transplant cardiologist at Columbia University in New York. Rather, the finding suggests that more research should be done to identify the determinants of survival in patients with nonischemic cardiomyopathy who are awaiting a heart transplant.

Her analysis focused on U.S. patients listed with the United Network for Organ Sharing as status 2 patients, defined as those who meet general criteria for a heart transplant, but are not “high urgency” status 1 patients.

During the period studied, use of ICDs in status 2 patients jumped more than twofold, rising from 37% in 2005 to 77% of listed status 2 patients in 2005, Dr. Lietz said. A total of 6,201 patients were listed as status 2 for a heart transplant in this period: 3,448 patients with ischemic-etiology cardiomyopathy and 2,753 patients with a nonischemic etiology. The vast majority (98%) of these patients who received an ICD had it implanted before they were listed for a heart transplant.

The 3-year survival rate of all patients with ischemic cardiomyopathy who had an ICD was 84%, compared with 76% among patients who did not receive an ICD. The researchers then ran the same analysis only on patients who remained on the list and did not receive a donated heart. In this subgroup, the 3-year survival rate with an ICD was 73.6%, and without an ICD it was 67.4%, a significant difference.

The 6.2% absolute improvement in survival over 3 years linked with ICD use was comparable with the survival benefit seen with ICD use in the Sudden Cardiac Death Heart Failure Trial (SCD-HFT), Dr. Lietz noted.

In contrast, among all patients with nonischemic cardiomyopathy who were listed as status 2, the 3-year survival rate with an ICD was 79.8%, compared with 81.2% among patients without an ICD, a “surprising” finding, said Dr. Lietz. This unexpected disparity remained among those who remained listed without a new heart. The survival rate was 65.7% with an ICD and 74.5% without an ICD, a difference that was not statistically significant, Dr. Lietz said.

Presence of an ICD did not affect the 3-year survival rate in status 2 patients with nonischemic cardiomyopathy. DR. LIETZ

BOSTON – Patients with three or more risk factors who were listed with the highest urgency for a heart transplant—status 1A—on the U.S. waiting list had at least a 30% risk of dying before a donor heart was available, based on actual experience during 2000–2006.

Records from the United Network for Organ Sharing (UNOS) for this period showed that when high-risk patients (defined as those with more than three risk factors for death) received a mechanical circulatory support device, their 90-day survival rate jumped from 50% to 89%, said Dr. Katherine Lietz, who presented an analysis of UNOS data at the annual meeting of the International Society for Heart and Lung Transplantation. When a ventricular assist implant is used this way, it's often called a “bridge-to-transplant” device.

“To bridge or not to bridge is one of the most challenging decisions for medically managed, high-urgency, status 1A patients” who are awaiting a heart transplant, said Dr. Lietz, a transplant cardiologist at Columbia University in New York. Three key factors enter into this decision: the patient's risk for dying while awaiting a donor heart, the chances for successfully receiving a transplanted heart, and the risk of complications from implantation with a mechanical circulatory support device.

To better document the first two factors, Dr. Lietz and her associates analyzed data collected on 1,755 patients who were listed with UNOS as status 1A candidates for a heart transplant during January 2000-December 2006. During their first 30 days on the UNOS list, 14% of the patients died, 49% received a transplanted heart, 33% remained active on the list, and the remaining 4% were removed from the list because their status had improved.

The investigators identified the following six clinical or demographic features that were significantly associated with an elevated risk for death during the first 30 days on the list: blood type O, age older than 60 years, ventilator support, intra-aortic balloon pump, serum creatinine greater than 1.5 mg/dL, and serum albumin less than 3.0 g/dL.

Further analysis showed that the risk of death increased in patients who had higher numbers of these risk factors. Patients with none of these risk factors had an 11% risk of dying while they were maintained on medical treatment during their first 30 days on the list. Mortality risk rates increased as the number of risk factors rose (see box).

A second analysis identified a non-O blood type and a body weight of 89 kg or less as the most important determinants of receiving a heart transplant during the first 30 days on the list. Patients who met both of these criteria had a 66% chance of receiving a heart during this period. Those with either one of these two factors had about a 50% chance, and patients without either factor had about a 23% chance of receiving a donated heart, Dr. Lietz said.

She stressed that patients and their physicians need to determine how these findings can be used to help guide individual decisions about whether to rely on medical treatment alone or opt for implantation of a mechanical circulatory support device while a patient is listed and awaiting a heart. Dr. Lietz suggested that a reasonable cutoff might be a risk for dying of 30% or greater while listed, which corresponds to a patient's having three or more mortality risk factors.

The UNOS data showed that these patients stood to substantially boost their chances for survival if they received a mechanical circulatory support device.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON – Patients with three or more risk factors who were listed with the highest urgency for a heart transplant—status 1A—on the U.S. waiting list had at least a 30% risk of dying before a donor heart was available, based on actual experience during 2000–2006.

Records from the United Network for Organ Sharing (UNOS) for this period showed that when high-risk patients (defined as those with more than three risk factors for death) received a mechanical circulatory support device, their 90-day survival rate jumped from 50% to 89%, said Dr. Katherine Lietz, who presented an analysis of UNOS data at the annual meeting of the International Society for Heart and Lung Transplantation. When a ventricular assist implant is used this way, it's often called a “bridge-to-transplant” device.

“To bridge or not to bridge is one of the most challenging decisions for medically managed, high-urgency, status 1A patients” who are awaiting a heart transplant, said Dr. Lietz, a transplant cardiologist at Columbia University in New York. Three key factors enter into this decision: the patient's risk for dying while awaiting a donor heart, the chances for successfully receiving a transplanted heart, and the risk of complications from implantation with a mechanical circulatory support device.

To better document the first two factors, Dr. Lietz and her associates analyzed data collected on 1,755 patients who were listed with UNOS as status 1A candidates for a heart transplant during January 2000-December 2006. During their first 30 days on the UNOS list, 14% of the patients died, 49% received a transplanted heart, 33% remained active on the list, and the remaining 4% were removed from the list because their status had improved.

The investigators identified the following six clinical or demographic features that were significantly associated with an elevated risk for death during the first 30 days on the list: blood type O, age older than 60 years, ventilator support, intra-aortic balloon pump, serum creatinine greater than 1.5 mg/dL, and serum albumin less than 3.0 g/dL.

Further analysis showed that the risk of death increased in patients who had higher numbers of these risk factors. Patients with none of these risk factors had an 11% risk of dying while they were maintained on medical treatment during their first 30 days on the list. Mortality risk rates increased as the number of risk factors rose (see box).

A second analysis identified a non-O blood type and a body weight of 89 kg or less as the most important determinants of receiving a heart transplant during the first 30 days on the list. Patients who met both of these criteria had a 66% chance of receiving a heart during this period. Those with either one of these two factors had about a 50% chance, and patients without either factor had about a 23% chance of receiving a donated heart, Dr. Lietz said.

She stressed that patients and their physicians need to determine how these findings can be used to help guide individual decisions about whether to rely on medical treatment alone or opt for implantation of a mechanical circulatory support device while a patient is listed and awaiting a heart. Dr. Lietz suggested that a reasonable cutoff might be a risk for dying of 30% or greater while listed, which corresponds to a patient's having three or more mortality risk factors.

The UNOS data showed that these patients stood to substantially boost their chances for survival if they received a mechanical circulatory support device.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON – Patients with three or more risk factors who were listed with the highest urgency for a heart transplant—status 1A—on the U.S. waiting list had at least a 30% risk of dying before a donor heart was available, based on actual experience during 2000–2006.

Records from the United Network for Organ Sharing (UNOS) for this period showed that when high-risk patients (defined as those with more than three risk factors for death) received a mechanical circulatory support device, their 90-day survival rate jumped from 50% to 89%, said Dr. Katherine Lietz, who presented an analysis of UNOS data at the annual meeting of the International Society for Heart and Lung Transplantation. When a ventricular assist implant is used this way, it's often called a “bridge-to-transplant” device.

“To bridge or not to bridge is one of the most challenging decisions for medically managed, high-urgency, status 1A patients” who are awaiting a heart transplant, said Dr. Lietz, a transplant cardiologist at Columbia University in New York. Three key factors enter into this decision: the patient's risk for dying while awaiting a donor heart, the chances for successfully receiving a transplanted heart, and the risk of complications from implantation with a mechanical circulatory support device.

To better document the first two factors, Dr. Lietz and her associates analyzed data collected on 1,755 patients who were listed with UNOS as status 1A candidates for a heart transplant during January 2000-December 2006. During their first 30 days on the UNOS list, 14% of the patients died, 49% received a transplanted heart, 33% remained active on the list, and the remaining 4% were removed from the list because their status had improved.

The investigators identified the following six clinical or demographic features that were significantly associated with an elevated risk for death during the first 30 days on the list: blood type O, age older than 60 years, ventilator support, intra-aortic balloon pump, serum creatinine greater than 1.5 mg/dL, and serum albumin less than 3.0 g/dL.

Further analysis showed that the risk of death increased in patients who had higher numbers of these risk factors. Patients with none of these risk factors had an 11% risk of dying while they were maintained on medical treatment during their first 30 days on the list. Mortality risk rates increased as the number of risk factors rose (see box).

A second analysis identified a non-O blood type and a body weight of 89 kg or less as the most important determinants of receiving a heart transplant during the first 30 days on the list. Patients who met both of these criteria had a 66% chance of receiving a heart during this period. Those with either one of these two factors had about a 50% chance, and patients without either factor had about a 23% chance of receiving a donated heart, Dr. Lietz said.

She stressed that patients and their physicians need to determine how these findings can be used to help guide individual decisions about whether to rely on medical treatment alone or opt for implantation of a mechanical circulatory support device while a patient is listed and awaiting a heart. Dr. Lietz suggested that a reasonable cutoff might be a risk for dying of 30% or greater while listed, which corresponds to a patient's having three or more mortality risk factors.

The UNOS data showed that these patients stood to substantially boost their chances for survival if they received a mechanical circulatory support device.

ELSEVIER GLOBAL MEDICAL NEWS

NEW YORK — Subclinical hypothyroidism with a thyroid-stimulating hormone level of 10–20 mU/L was associated with an almost twofold risk of clinical heart failure in a study of more than 3,000 older adults.

The findings, presented by Dr. Douglas Bauer at the annual meeting of the American Thyroid Association, come from an analysis of participants in the prospective Cardiovascular Health Study, which includes persons from Medicare population-based listings at four university hospitals in the United States and is funded by the National Institutes of Health.

Dr. Bauer and his colleagues recruited 3,065 participants who were free of heart failure at baseline and not taking any medication known to affect thyroid function. Any participants who initiated T4 replacement during the study were removed from the analysis, and 21 were excluded because of insufficient serum for testing. Participants were followed for 12 years and were contacted every 6 months for assessment of outcomes, said Dr. Bauer of the University of California, San Francisco.

Of the 495 persons (16%) with hypothyroidism, 448 had a TSH level between 4.5 mU/L and 9.9 mU/L and 47 had a TSH level of 10–20 mU/L. Hyperthyroidism (TSH level below 0.45 mU/L and normal T4 value) was found in 44 persons. All hypothyroidism and hyperthyroidism in the study was subclinical.

Echocardiograms were obtained for all participants at baseline and at 5 years' follow-up and read by blinded clinicians (including cardiologists). Some participants experienced heart failure before the 5-year follow-up, and their clinical echocardiograms were also included.

At 12 years' follow-up, 660 persons (22%) had heart failure. In the 47 participants with a TSH level of 10–20 mU/L, there were 45 heart failure events per 1,000 person-years, compared with 22 events per 1,000 person-years in euthyroid participants. Multivariate analysis showed an unadjusted hazard ratio of 2.03 for those with a TSH level of 10–20 mU/L, versus euthyroid participants—a significant difference. (Adjusted for confounding factors, the hazard ratio was 1.88.) No increase in heart failure risk was seen in the hypothyroid participants with TSH levels of 4.5–9.9 mU/L or in euthyroid persons, versus those with TSH levels below that range. There was no difference in the heart failure rate between men and women.

Moreover, at 12 years, impaired cardiac function was associated with TSH levels of 10–20 mU/L: The percentage of participants who had an abnormal left ventricular ejection fraction at time of incident heart failure was 80% in the high-TSH hypothyroid group, compared with 39% in the lower-TSH hypothyroid group, 44% in the euthyroid group, and 33% in the hyperthyroid group.

Dr. Bauer and colleagues concluded that “subclinical hypothyroidism is associated with a moderately increased risk of clinical events of congestive heart failure among older individuals with a TSH greater than 10 [mU/L].”

He acknowledged that the study was limited by a shorter follow-up period for the echocardiography data than for the heart failure data (5 years vs. 12 years), as well as missing follow-up echocardiograms for some participants.

Several studies have established an association between subclinical hypothyroid and hyperthyroid disease and cardiac dysfunction, Dr. Bauer said. But most studies have looked at subtle abnormalities in contractility, rather than at more clinically important measures, such as left ventricular ejection fraction. Also, most of those studies have been limited by small sample sizes and lack of randomization.

NEW YORK — Subclinical hypothyroidism with a thyroid-stimulating hormone level of 10–20 mU/L was associated with an almost twofold risk of clinical heart failure in a study of more than 3,000 older adults.

The findings, presented by Dr. Douglas Bauer at the annual meeting of the American Thyroid Association, come from an analysis of participants in the prospective Cardiovascular Health Study, which includes persons from Medicare population-based listings at four university hospitals in the United States and is funded by the National Institutes of Health.

Dr. Bauer and his colleagues recruited 3,065 participants who were free of heart failure at baseline and not taking any medication known to affect thyroid function. Any participants who initiated T4 replacement during the study were removed from the analysis, and 21 were excluded because of insufficient serum for testing. Participants were followed for 12 years and were contacted every 6 months for assessment of outcomes, said Dr. Bauer of the University of California, San Francisco.

Of the 495 persons (16%) with hypothyroidism, 448 had a TSH level between 4.5 mU/L and 9.9 mU/L and 47 had a TSH level of 10–20 mU/L. Hyperthyroidism (TSH level below 0.45 mU/L and normal T4 value) was found in 44 persons. All hypothyroidism and hyperthyroidism in the study was subclinical.

Echocardiograms were obtained for all participants at baseline and at 5 years' follow-up and read by blinded clinicians (including cardiologists). Some participants experienced heart failure before the 5-year follow-up, and their clinical echocardiograms were also included.

At 12 years' follow-up, 660 persons (22%) had heart failure. In the 47 participants with a TSH level of 10–20 mU/L, there were 45 heart failure events per 1,000 person-years, compared with 22 events per 1,000 person-years in euthyroid participants. Multivariate analysis showed an unadjusted hazard ratio of 2.03 for those with a TSH level of 10–20 mU/L, versus euthyroid participants—a significant difference. (Adjusted for confounding factors, the hazard ratio was 1.88.) No increase in heart failure risk was seen in the hypothyroid participants with TSH levels of 4.5–9.9 mU/L or in euthyroid persons, versus those with TSH levels below that range. There was no difference in the heart failure rate between men and women.

Moreover, at 12 years, impaired cardiac function was associated with TSH levels of 10–20 mU/L: The percentage of participants who had an abnormal left ventricular ejection fraction at time of incident heart failure was 80% in the high-TSH hypothyroid group, compared with 39% in the lower-TSH hypothyroid group, 44% in the euthyroid group, and 33% in the hyperthyroid group.

Dr. Bauer and colleagues concluded that “subclinical hypothyroidism is associated with a moderately increased risk of clinical events of congestive heart failure among older individuals with a TSH greater than 10 [mU/L].”

He acknowledged that the study was limited by a shorter follow-up period for the echocardiography data than for the heart failure data (5 years vs. 12 years), as well as missing follow-up echocardiograms for some participants.

Several studies have established an association between subclinical hypothyroid and hyperthyroid disease and cardiac dysfunction, Dr. Bauer said. But most studies have looked at subtle abnormalities in contractility, rather than at more clinically important measures, such as left ventricular ejection fraction. Also, most of those studies have been limited by small sample sizes and lack of randomization.

NEW YORK — Subclinical hypothyroidism with a thyroid-stimulating hormone level of 10–20 mU/L was associated with an almost twofold risk of clinical heart failure in a study of more than 3,000 older adults.

The findings, presented by Dr. Douglas Bauer at the annual meeting of the American Thyroid Association, come from an analysis of participants in the prospective Cardiovascular Health Study, which includes persons from Medicare population-based listings at four university hospitals in the United States and is funded by the National Institutes of Health.

Dr. Bauer and his colleagues recruited 3,065 participants who were free of heart failure at baseline and not taking any medication known to affect thyroid function. Any participants who initiated T4 replacement during the study were removed from the analysis, and 21 were excluded because of insufficient serum for testing. Participants were followed for 12 years and were contacted every 6 months for assessment of outcomes, said Dr. Bauer of the University of California, San Francisco.

Of the 495 persons (16%) with hypothyroidism, 448 had a TSH level between 4.5 mU/L and 9.9 mU/L and 47 had a TSH level of 10–20 mU/L. Hyperthyroidism (TSH level below 0.45 mU/L and normal T4 value) was found in 44 persons. All hypothyroidism and hyperthyroidism in the study was subclinical.

Echocardiograms were obtained for all participants at baseline and at 5 years' follow-up and read by blinded clinicians (including cardiologists). Some participants experienced heart failure before the 5-year follow-up, and their clinical echocardiograms were also included.

At 12 years' follow-up, 660 persons (22%) had heart failure. In the 47 participants with a TSH level of 10–20 mU/L, there were 45 heart failure events per 1,000 person-years, compared with 22 events per 1,000 person-years in euthyroid participants. Multivariate analysis showed an unadjusted hazard ratio of 2.03 for those with a TSH level of 10–20 mU/L, versus euthyroid participants—a significant difference. (Adjusted for confounding factors, the hazard ratio was 1.88.) No increase in heart failure risk was seen in the hypothyroid participants with TSH levels of 4.5–9.9 mU/L or in euthyroid persons, versus those with TSH levels below that range. There was no difference in the heart failure rate between men and women.

Moreover, at 12 years, impaired cardiac function was associated with TSH levels of 10–20 mU/L: The percentage of participants who had an abnormal left ventricular ejection fraction at time of incident heart failure was 80% in the high-TSH hypothyroid group, compared with 39% in the lower-TSH hypothyroid group, 44% in the euthyroid group, and 33% in the hyperthyroid group.

Dr. Bauer and colleagues concluded that “subclinical hypothyroidism is associated with a moderately increased risk of clinical events of congestive heart failure among older individuals with a TSH greater than 10 [mU/L].”

He acknowledged that the study was limited by a shorter follow-up period for the echocardiography data than for the heart failure data (5 years vs. 12 years), as well as missing follow-up echocardiograms for some participants.

Several studies have established an association between subclinical hypothyroid and hyperthyroid disease and cardiac dysfunction, Dr. Bauer said. But most studies have looked at subtle abnormalities in contractility, rather than at more clinically important measures, such as left ventricular ejection fraction. Also, most of those studies have been limited by small sample sizes and lack of randomization.