Heart Failure

WASHINGTON — Short-term use of a percutaneous ventricular assist device during high-risk surgery or in cases of near-death heart failure can help support patients long enough for them to recover or receive additional treatment, Reynolds M. Delgado III, M.D., said at the annual conference of the American Society for Artificial Internal Organs.

Dr. Delgado and his colleagues at the Texas Heart Institute have used the TandemHeart in four different scenarios as:

▸ A supportive device during high-risk percutaneous transluminal coronary angioplasty in nine patients.

▸ A bridge to recovery in two patients with acute cardiogenic shock.

▸ Circulatory support in five patients during high-risk cardiac surgery (coronary artery bypass and/or mitral valve surgery).

▸ A bridge to an implanted left ventricular assist device (LVAD) in seven patients.

Blood flow in the TandemHeart, made by CardiacAssist Inc., follows a path from a cannula in the femoral vein that pierces the intraatrial septum and takes oxygenated blood from the left atrium back to a continuously flowing extracorporeal pump (attached to the patient's leg), which distributes the blood through a cannula in one or both femoral arteries.

“The tricky part of this procedure is the transseptal cannulation; putting this venous catheter across the septum requires some special skill. A subset of cardiologists are able to do this—perhaps 10% or less,” said Dr. Delgado, medical director of mechanical assist devices in heart failure at the institute, located at St. Luke's Episcopal Hospital, Houston.

None of the high-risk percutaneous transluminal coronary angioplasty patients were candidates for surgery. They had high-risk coronary anatomy and were at risk for imminent death without intervention. The investigators successfully performed the procedure without complications in eight of these nine patients; one patient had a perforated left atrium. Overall, eight patients were discharged from the hospital with good long-term outcomes while one patient died of multiorgan failure after surgery, said Dr. Delgado, a cardiologist. Dr. Delgado reported that he was an investigator on a previous trial sponsored by CardiacAssist but has no financial conflicts of interest with the company.

Both cardiogenic shock patients successfully underwent the implantation procedure. After 7 days, one patient successfully recovered from heart failure due to acute myocarditis. The other patient initially suffered an acute MI and then cardiac arrest just prior to implantation of the TandemHeart; the patient died despite successful implantation.

Of five patients who underwent high-risk cardiac surgery, all had successful implantation, but one patient with coagulopathy and multiorgan failure died of major intraoperative bleeding.

Seven patients were successfully bridged from the TandemHeart to an LVAD. However, four of these patients did not survive long term with an LVAD, primarily because of multiorgan failure that existed prior to the implantation of the TandemHeart.

On average, the 23 patients in the study were aged 68 years and were on percutaneous ventricular assist device support for 2.8 days; 20 patients were male.

WASHINGTON — Short-term use of a percutaneous ventricular assist device during high-risk surgery or in cases of near-death heart failure can help support patients long enough for them to recover or receive additional treatment, Reynolds M. Delgado III, M.D., said at the annual conference of the American Society for Artificial Internal Organs.

Dr. Delgado and his colleagues at the Texas Heart Institute have used the TandemHeart in four different scenarios as:

▸ A supportive device during high-risk percutaneous transluminal coronary angioplasty in nine patients.

▸ A bridge to recovery in two patients with acute cardiogenic shock.

▸ Circulatory support in five patients during high-risk cardiac surgery (coronary artery bypass and/or mitral valve surgery).

▸ A bridge to an implanted left ventricular assist device (LVAD) in seven patients.

Blood flow in the TandemHeart, made by CardiacAssist Inc., follows a path from a cannula in the femoral vein that pierces the intraatrial septum and takes oxygenated blood from the left atrium back to a continuously flowing extracorporeal pump (attached to the patient's leg), which distributes the blood through a cannula in one or both femoral arteries.

“The tricky part of this procedure is the transseptal cannulation; putting this venous catheter across the septum requires some special skill. A subset of cardiologists are able to do this—perhaps 10% or less,” said Dr. Delgado, medical director of mechanical assist devices in heart failure at the institute, located at St. Luke's Episcopal Hospital, Houston.

None of the high-risk percutaneous transluminal coronary angioplasty patients were candidates for surgery. They had high-risk coronary anatomy and were at risk for imminent death without intervention. The investigators successfully performed the procedure without complications in eight of these nine patients; one patient had a perforated left atrium. Overall, eight patients were discharged from the hospital with good long-term outcomes while one patient died of multiorgan failure after surgery, said Dr. Delgado, a cardiologist. Dr. Delgado reported that he was an investigator on a previous trial sponsored by CardiacAssist but has no financial conflicts of interest with the company.

Both cardiogenic shock patients successfully underwent the implantation procedure. After 7 days, one patient successfully recovered from heart failure due to acute myocarditis. The other patient initially suffered an acute MI and then cardiac arrest just prior to implantation of the TandemHeart; the patient died despite successful implantation.

Of five patients who underwent high-risk cardiac surgery, all had successful implantation, but one patient with coagulopathy and multiorgan failure died of major intraoperative bleeding.

Seven patients were successfully bridged from the TandemHeart to an LVAD. However, four of these patients did not survive long term with an LVAD, primarily because of multiorgan failure that existed prior to the implantation of the TandemHeart.

On average, the 23 patients in the study were aged 68 years and were on percutaneous ventricular assist device support for 2.8 days; 20 patients were male.

WASHINGTON — Short-term use of a percutaneous ventricular assist device during high-risk surgery or in cases of near-death heart failure can help support patients long enough for them to recover or receive additional treatment, Reynolds M. Delgado III, M.D., said at the annual conference of the American Society for Artificial Internal Organs.

Dr. Delgado and his colleagues at the Texas Heart Institute have used the TandemHeart in four different scenarios as:

▸ A supportive device during high-risk percutaneous transluminal coronary angioplasty in nine patients.

▸ A bridge to recovery in two patients with acute cardiogenic shock.

▸ Circulatory support in five patients during high-risk cardiac surgery (coronary artery bypass and/or mitral valve surgery).

▸ A bridge to an implanted left ventricular assist device (LVAD) in seven patients.

Blood flow in the TandemHeart, made by CardiacAssist Inc., follows a path from a cannula in the femoral vein that pierces the intraatrial septum and takes oxygenated blood from the left atrium back to a continuously flowing extracorporeal pump (attached to the patient's leg), which distributes the blood through a cannula in one or both femoral arteries.

“The tricky part of this procedure is the transseptal cannulation; putting this venous catheter across the septum requires some special skill. A subset of cardiologists are able to do this—perhaps 10% or less,” said Dr. Delgado, medical director of mechanical assist devices in heart failure at the institute, located at St. Luke's Episcopal Hospital, Houston.

None of the high-risk percutaneous transluminal coronary angioplasty patients were candidates for surgery. They had high-risk coronary anatomy and were at risk for imminent death without intervention. The investigators successfully performed the procedure without complications in eight of these nine patients; one patient had a perforated left atrium. Overall, eight patients were discharged from the hospital with good long-term outcomes while one patient died of multiorgan failure after surgery, said Dr. Delgado, a cardiologist. Dr. Delgado reported that he was an investigator on a previous trial sponsored by CardiacAssist but has no financial conflicts of interest with the company.

Both cardiogenic shock patients successfully underwent the implantation procedure. After 7 days, one patient successfully recovered from heart failure due to acute myocarditis. The other patient initially suffered an acute MI and then cardiac arrest just prior to implantation of the TandemHeart; the patient died despite successful implantation.

Of five patients who underwent high-risk cardiac surgery, all had successful implantation, but one patient with coagulopathy and multiorgan failure died of major intraoperative bleeding.

Seven patients were successfully bridged from the TandemHeart to an LVAD. However, four of these patients did not survive long term with an LVAD, primarily because of multiorgan failure that existed prior to the implantation of the TandemHeart.

On average, the 23 patients in the study were aged 68 years and were on percutaneous ventricular assist device support for 2.8 days; 20 patients were male.

ORLANDO, FLA. — A standard 7-week course of enhanced external counterpulsation therapy in patients with heart failure who are on optimal pharmacotherapy improves their exercise duration, quality of life, and New York Heart Association class for at least 6 months afterward, according to the results of a randomized trial presented at the annual meeting of the American College of Cardiology.

“We believe these results suggest that EECP provides adjunctive therapy in patients with New York Heart Association [NYHA] class II-III heart failure receiving optimal pharmacologic therapy,” said Arthur M. Feldman, M.D., chairman of the steering committee for the Prospective Evaluation of EECP in Congestive Heart failure (PEECH) trial.

PEECH involved 187 patients with systolic heart failure (HF) and a mean ejection fraction of 26% who were randomized at 29 medical centers to optimal drug therapy alone or in combination with 35 hour-long EECP sessions over 7 weeks. Patients were unblinded as to their treatment allocation, as were their treating physicians; however, a separate group of blinded investigators performed all patient evaluations, explained Dr. Feldman, professor and chairman of the department of medicine at Thomas Jefferson University, Philadelphia.

The primary end point of the study was at least a 60-second improvement in exercise duration at follow-up 6 months after the last EECP session. This was achieved in 35% of the EECP group and 25% of the control patients, a significant difference. However, there was no between-group difference in a predefined alternative primary end point, which was the percentage of patients achieving at least a 1.25-mL/kg per minute increase in peak oxygen consumption (VO₂).

Exercise duration improved by a mean of 25 seconds in the EECP group, whereas it declined by 10 seconds in controls. To put this 35-second difference into perspective, Dr. Feldman said that randomized trials of cardiac resynchronization therapy show it typically results in roughly a 50-second differential in exercise duration, compared with sham therapy.

Improvement in NYHA class was a secondary PEECH end point. At 6 months, 31% of the EECP patients, and only 14% of control patients showed at least a one-class improvement.

Another secondary end point was quality of life as measured in terms of change from baseline in scores on the Minnesota Living with Heart Failure questionnaire. One month after completion of the EECP sessions, treated patients had a mean 8.9-point improvement, compared with a 3.4-point gain in control patients. The quality of life advantage favoring the EECP group remained significant at 3 months, but not at 6 months.

EECP treatment was well tolerated, although one patient developed a pulmonary embolism that investigators believed was therapy related.

Discussant Andrew D. Michaels, M.D., characterized the PEECH results as “mixed.”

“The trial met one of two primary end points. It's somewhat concerning that the end points that were met—namely increased exercise duration, improved quality of life, and improvement in [NYHA] class—are all subject to the placebo effect,” added Dr. Michaels of the University of California, San Francisco.

Dr. Feldman said that although EECP resulted in a significant gain in VO₂ in an earlier pilot study, the PEECH population may have been biased against realizing a similar benefit because they were predominantly NYHA class II and hence did not have a long way to go to reach an essentially normal response.

EECP utilizes a series of ECG-synchronized inflatable cuffs wrapped around the legs. The cuffs swiftly inflate at onset of diastole and rapidly deflate at onset of systole, providing hemodynamic effects similar to intraaortic balloon counterpulsation, including increased coronary artery blood flow along with afterload reduction.

Enhanced external counterpulsation therapy is approved for the treatment of stable angina. The average payment to physicians under Medicare is $138.34 per session.

Both Dr. Feldman and Dr. Michaels are consultants to Vasomedical Inc., which markets EECP systems and sponsored the PEECH trial.

ORLANDO, FLA. — A standard 7-week course of enhanced external counterpulsation therapy in patients with heart failure who are on optimal pharmacotherapy improves their exercise duration, quality of life, and New York Heart Association class for at least 6 months afterward, according to the results of a randomized trial presented at the annual meeting of the American College of Cardiology.

“We believe these results suggest that EECP provides adjunctive therapy in patients with New York Heart Association [NYHA] class II-III heart failure receiving optimal pharmacologic therapy,” said Arthur M. Feldman, M.D., chairman of the steering committee for the Prospective Evaluation of EECP in Congestive Heart failure (PEECH) trial.

PEECH involved 187 patients with systolic heart failure (HF) and a mean ejection fraction of 26% who were randomized at 29 medical centers to optimal drug therapy alone or in combination with 35 hour-long EECP sessions over 7 weeks. Patients were unblinded as to their treatment allocation, as were their treating physicians; however, a separate group of blinded investigators performed all patient evaluations, explained Dr. Feldman, professor and chairman of the department of medicine at Thomas Jefferson University, Philadelphia.

The primary end point of the study was at least a 60-second improvement in exercise duration at follow-up 6 months after the last EECP session. This was achieved in 35% of the EECP group and 25% of the control patients, a significant difference. However, there was no between-group difference in a predefined alternative primary end point, which was the percentage of patients achieving at least a 1.25-mL/kg per minute increase in peak oxygen consumption (VO₂).

Exercise duration improved by a mean of 25 seconds in the EECP group, whereas it declined by 10 seconds in controls. To put this 35-second difference into perspective, Dr. Feldman said that randomized trials of cardiac resynchronization therapy show it typically results in roughly a 50-second differential in exercise duration, compared with sham therapy.

Improvement in NYHA class was a secondary PEECH end point. At 6 months, 31% of the EECP patients, and only 14% of control patients showed at least a one-class improvement.

Another secondary end point was quality of life as measured in terms of change from baseline in scores on the Minnesota Living with Heart Failure questionnaire. One month after completion of the EECP sessions, treated patients had a mean 8.9-point improvement, compared with a 3.4-point gain in control patients. The quality of life advantage favoring the EECP group remained significant at 3 months, but not at 6 months.

EECP treatment was well tolerated, although one patient developed a pulmonary embolism that investigators believed was therapy related.

Discussant Andrew D. Michaels, M.D., characterized the PEECH results as “mixed.”

“The trial met one of two primary end points. It's somewhat concerning that the end points that were met—namely increased exercise duration, improved quality of life, and improvement in [NYHA] class—are all subject to the placebo effect,” added Dr. Michaels of the University of California, San Francisco.

Dr. Feldman said that although EECP resulted in a significant gain in VO₂ in an earlier pilot study, the PEECH population may have been biased against realizing a similar benefit because they were predominantly NYHA class II and hence did not have a long way to go to reach an essentially normal response.

EECP utilizes a series of ECG-synchronized inflatable cuffs wrapped around the legs. The cuffs swiftly inflate at onset of diastole and rapidly deflate at onset of systole, providing hemodynamic effects similar to intraaortic balloon counterpulsation, including increased coronary artery blood flow along with afterload reduction.

Enhanced external counterpulsation therapy is approved for the treatment of stable angina. The average payment to physicians under Medicare is $138.34 per session.

Both Dr. Feldman and Dr. Michaels are consultants to Vasomedical Inc., which markets EECP systems and sponsored the PEECH trial.

ORLANDO, FLA. — A standard 7-week course of enhanced external counterpulsation therapy in patients with heart failure who are on optimal pharmacotherapy improves their exercise duration, quality of life, and New York Heart Association class for at least 6 months afterward, according to the results of a randomized trial presented at the annual meeting of the American College of Cardiology.

“We believe these results suggest that EECP provides adjunctive therapy in patients with New York Heart Association [NYHA] class II-III heart failure receiving optimal pharmacologic therapy,” said Arthur M. Feldman, M.D., chairman of the steering committee for the Prospective Evaluation of EECP in Congestive Heart failure (PEECH) trial.

PEECH involved 187 patients with systolic heart failure (HF) and a mean ejection fraction of 26% who were randomized at 29 medical centers to optimal drug therapy alone or in combination with 35 hour-long EECP sessions over 7 weeks. Patients were unblinded as to their treatment allocation, as were their treating physicians; however, a separate group of blinded investigators performed all patient evaluations, explained Dr. Feldman, professor and chairman of the department of medicine at Thomas Jefferson University, Philadelphia.

The primary end point of the study was at least a 60-second improvement in exercise duration at follow-up 6 months after the last EECP session. This was achieved in 35% of the EECP group and 25% of the control patients, a significant difference. However, there was no between-group difference in a predefined alternative primary end point, which was the percentage of patients achieving at least a 1.25-mL/kg per minute increase in peak oxygen consumption (VO₂).

Exercise duration improved by a mean of 25 seconds in the EECP group, whereas it declined by 10 seconds in controls. To put this 35-second difference into perspective, Dr. Feldman said that randomized trials of cardiac resynchronization therapy show it typically results in roughly a 50-second differential in exercise duration, compared with sham therapy.

Improvement in NYHA class was a secondary PEECH end point. At 6 months, 31% of the EECP patients, and only 14% of control patients showed at least a one-class improvement.

Another secondary end point was quality of life as measured in terms of change from baseline in scores on the Minnesota Living with Heart Failure questionnaire. One month after completion of the EECP sessions, treated patients had a mean 8.9-point improvement, compared with a 3.4-point gain in control patients. The quality of life advantage favoring the EECP group remained significant at 3 months, but not at 6 months.

EECP treatment was well tolerated, although one patient developed a pulmonary embolism that investigators believed was therapy related.

Discussant Andrew D. Michaels, M.D., characterized the PEECH results as “mixed.”

“The trial met one of two primary end points. It's somewhat concerning that the end points that were met—namely increased exercise duration, improved quality of life, and improvement in [NYHA] class—are all subject to the placebo effect,” added Dr. Michaels of the University of California, San Francisco.

Dr. Feldman said that although EECP resulted in a significant gain in VO₂ in an earlier pilot study, the PEECH population may have been biased against realizing a similar benefit because they were predominantly NYHA class II and hence did not have a long way to go to reach an essentially normal response.

EECP utilizes a series of ECG-synchronized inflatable cuffs wrapped around the legs. The cuffs swiftly inflate at onset of diastole and rapidly deflate at onset of systole, providing hemodynamic effects similar to intraaortic balloon counterpulsation, including increased coronary artery blood flow along with afterload reduction.

Enhanced external counterpulsation therapy is approved for the treatment of stable angina. The average payment to physicians under Medicare is $138.34 per session.

Both Dr. Feldman and Dr. Michaels are consultants to Vasomedical Inc., which markets EECP systems and sponsored the PEECH trial.

WASHINGTON — Body temperature below 36° C at hospital admission was independently associated with a lower survival rate in a study of 56,659 patients with advanced heart failure.

Disordered thermoregulation is common in patients with advanced heart failure, and body temperature measurements may improve risk assessment in these patients, Brahmajee K. Nallamothu, M.D., wrote in a poster presented at the Clinical Research 2005 meeting sponsored by the American Federation for Medical Research.

Dr. Nallamothu, a cardiologist at the University of Michigan, Ann Arbor, and his associates reviewed data on patients aged 65 years and older who were participating in the National Heart Care Project.

The mean body temperature upon hospital admission was 36.5° C, and most of the patients' admission temperatures were between 36° C and 38° C. However, 10,754 (18.5%) of the patients had body temperatures below 36° C and 1,145 (1.9%) had body temperatures above 38° C.

After multivariate analysis, patients with body temperatures below 36° C had significantly higher mortality, both in hospital (adjusted risk ratio, 1.28) and at 1 year after their hospitalizations (adjusted risk ratio, 1.14). Body temperatures above 38° C were not significantly associated with in-hospital mortality, but they were significantly associated with lower mortality after 1 year (adjusted risk ratio, 0.80).

WASHINGTON — Body temperature below 36° C at hospital admission was independently associated with a lower survival rate in a study of 56,659 patients with advanced heart failure.

Disordered thermoregulation is common in patients with advanced heart failure, and body temperature measurements may improve risk assessment in these patients, Brahmajee K. Nallamothu, M.D., wrote in a poster presented at the Clinical Research 2005 meeting sponsored by the American Federation for Medical Research.

Dr. Nallamothu, a cardiologist at the University of Michigan, Ann Arbor, and his associates reviewed data on patients aged 65 years and older who were participating in the National Heart Care Project.

The mean body temperature upon hospital admission was 36.5° C, and most of the patients' admission temperatures were between 36° C and 38° C. However, 10,754 (18.5%) of the patients had body temperatures below 36° C and 1,145 (1.9%) had body temperatures above 38° C.

After multivariate analysis, patients with body temperatures below 36° C had significantly higher mortality, both in hospital (adjusted risk ratio, 1.28) and at 1 year after their hospitalizations (adjusted risk ratio, 1.14). Body temperatures above 38° C were not significantly associated with in-hospital mortality, but they were significantly associated with lower mortality after 1 year (adjusted risk ratio, 0.80).

WASHINGTON — Body temperature below 36° C at hospital admission was independently associated with a lower survival rate in a study of 56,659 patients with advanced heart failure.

Disordered thermoregulation is common in patients with advanced heart failure, and body temperature measurements may improve risk assessment in these patients, Brahmajee K. Nallamothu, M.D., wrote in a poster presented at the Clinical Research 2005 meeting sponsored by the American Federation for Medical Research.

Dr. Nallamothu, a cardiologist at the University of Michigan, Ann Arbor, and his associates reviewed data on patients aged 65 years and older who were participating in the National Heart Care Project.

The mean body temperature upon hospital admission was 36.5° C, and most of the patients' admission temperatures were between 36° C and 38° C. However, 10,754 (18.5%) of the patients had body temperatures below 36° C and 1,145 (1.9%) had body temperatures above 38° C.

After multivariate analysis, patients with body temperatures below 36° C had significantly higher mortality, both in hospital (adjusted risk ratio, 1.28) and at 1 year after their hospitalizations (adjusted risk ratio, 1.14). Body temperatures above 38° C were not significantly associated with in-hospital mortality, but they were significantly associated with lower mortality after 1 year (adjusted risk ratio, 0.80).

Candesartan's heart failure indication has been expanded by the Food and Drug Administration to include patients who are on ACE inhibitor therapy.

The angiotensin receptor blocker (ARB) was approved for a narrower heart failure indication in February, for patients with New York Heart Association (NYHA) class II-IV disease and a left ventricular ejection fraction (LVEF) of 40% or less to reduce cardiovascular death and heart failure hospitalizations, based largely on the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM)-Alternative trial, in which cardiovascular death or heart failure hospitalization, the primary end point, was reduced by 23% in those on candesartan, compared with those on placebo.

In May, the FDA approved the addition of the following statement to the heart failure indication in the drug's label: “Atacand also has an added effect on these outcomes when used with an ACE inhibitor.”

Candesartan, marketed as Atacand by AstraZeneca, was approved for treating hypertension in 1998. It is the first ARB approved for use with an ACE inhibitor for treating heart failure.

The latest approval was based on the results of the CHARM-Added trial, which showed that candesartan “adds a meaningful and important additional clinical benefit on top of other proven treatments, including β-blockers and ACE inhibitors,” Christopher Granger, M.D., director of the cardiac care unit at Duke University, Durham, N.C., and a member of the CHARM executive committee, said in an interview.

The relative risk of cardiovascular mortality or heart failure hospitalization was reduced by 15% in those on candesartan during a median follow-up of 41 months in CHARM-Added, which compared candesartan to placebo in 2,548 patients with NYHA class II-IV heart failure and an LVEF of 40% or less who were on an ACE inhibitor and standard therapy. Benefits were also seen in patients treated with β-blockers, suggesting there were no adverse interactions between β-blockers, candesartan, and ACE inhibitors.

Improved quality of life was also seen in the study, said Dr. Granger, who was a consultant to AstraZeneca for the FDA's cardiovascular and renal drugs advisory committee meeting in February, where the panel unanimously recommended approval of candesartan for this population of patients on an ACE inhibitor (CARDIOLOGY NEWS, April 2005, p. 10).

The recommended starting dose of candesartan for patients with heart failure is 4 mg/day, with a target dose of 32 mg once daily, achieved by doubling the dose about every 2 weeks, as tolerated.

In the CHARM studies, rates of hypotension, abnormal renal function, and hyperkalemia were higher in those on candesartan, as expected, due to a greater degree of renin-angiotensin-aldosterone system inhibition. Clinicians should monitor for hyperkalemia and renal insufficiency, especially when starting and titrating treatment, Dr. Granger advised.

Candesartan's heart failure indication has been expanded by the Food and Drug Administration to include patients who are on ACE inhibitor therapy.

The angiotensin receptor blocker (ARB) was approved for a narrower heart failure indication in February, for patients with New York Heart Association (NYHA) class II-IV disease and a left ventricular ejection fraction (LVEF) of 40% or less to reduce cardiovascular death and heart failure hospitalizations, based largely on the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM)-Alternative trial, in which cardiovascular death or heart failure hospitalization, the primary end point, was reduced by 23% in those on candesartan, compared with those on placebo.

In May, the FDA approved the addition of the following statement to the heart failure indication in the drug's label: “Atacand also has an added effect on these outcomes when used with an ACE inhibitor.”

Candesartan, marketed as Atacand by AstraZeneca, was approved for treating hypertension in 1998. It is the first ARB approved for use with an ACE inhibitor for treating heart failure.

The latest approval was based on the results of the CHARM-Added trial, which showed that candesartan “adds a meaningful and important additional clinical benefit on top of other proven treatments, including β-blockers and ACE inhibitors,” Christopher Granger, M.D., director of the cardiac care unit at Duke University, Durham, N.C., and a member of the CHARM executive committee, said in an interview.

The relative risk of cardiovascular mortality or heart failure hospitalization was reduced by 15% in those on candesartan during a median follow-up of 41 months in CHARM-Added, which compared candesartan to placebo in 2,548 patients with NYHA class II-IV heart failure and an LVEF of 40% or less who were on an ACE inhibitor and standard therapy. Benefits were also seen in patients treated with β-blockers, suggesting there were no adverse interactions between β-blockers, candesartan, and ACE inhibitors.

Improved quality of life was also seen in the study, said Dr. Granger, who was a consultant to AstraZeneca for the FDA's cardiovascular and renal drugs advisory committee meeting in February, where the panel unanimously recommended approval of candesartan for this population of patients on an ACE inhibitor (CARDIOLOGY NEWS, April 2005, p. 10).

The recommended starting dose of candesartan for patients with heart failure is 4 mg/day, with a target dose of 32 mg once daily, achieved by doubling the dose about every 2 weeks, as tolerated.

In the CHARM studies, rates of hypotension, abnormal renal function, and hyperkalemia were higher in those on candesartan, as expected, due to a greater degree of renin-angiotensin-aldosterone system inhibition. Clinicians should monitor for hyperkalemia and renal insufficiency, especially when starting and titrating treatment, Dr. Granger advised.

Candesartan's heart failure indication has been expanded by the Food and Drug Administration to include patients who are on ACE inhibitor therapy.

The angiotensin receptor blocker (ARB) was approved for a narrower heart failure indication in February, for patients with New York Heart Association (NYHA) class II-IV disease and a left ventricular ejection fraction (LVEF) of 40% or less to reduce cardiovascular death and heart failure hospitalizations, based largely on the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM)-Alternative trial, in which cardiovascular death or heart failure hospitalization, the primary end point, was reduced by 23% in those on candesartan, compared with those on placebo.

In May, the FDA approved the addition of the following statement to the heart failure indication in the drug's label: “Atacand also has an added effect on these outcomes when used with an ACE inhibitor.”

Candesartan, marketed as Atacand by AstraZeneca, was approved for treating hypertension in 1998. It is the first ARB approved for use with an ACE inhibitor for treating heart failure.

The latest approval was based on the results of the CHARM-Added trial, which showed that candesartan “adds a meaningful and important additional clinical benefit on top of other proven treatments, including β-blockers and ACE inhibitors,” Christopher Granger, M.D., director of the cardiac care unit at Duke University, Durham, N.C., and a member of the CHARM executive committee, said in an interview.

The relative risk of cardiovascular mortality or heart failure hospitalization was reduced by 15% in those on candesartan during a median follow-up of 41 months in CHARM-Added, which compared candesartan to placebo in 2,548 patients with NYHA class II-IV heart failure and an LVEF of 40% or less who were on an ACE inhibitor and standard therapy. Benefits were also seen in patients treated with β-blockers, suggesting there were no adverse interactions between β-blockers, candesartan, and ACE inhibitors.

Improved quality of life was also seen in the study, said Dr. Granger, who was a consultant to AstraZeneca for the FDA's cardiovascular and renal drugs advisory committee meeting in February, where the panel unanimously recommended approval of candesartan for this population of patients on an ACE inhibitor (CARDIOLOGY NEWS, April 2005, p. 10).

The recommended starting dose of candesartan for patients with heart failure is 4 mg/day, with a target dose of 32 mg once daily, achieved by doubling the dose about every 2 weeks, as tolerated.

In the CHARM studies, rates of hypotension, abnormal renal function, and hyperkalemia were higher in those on candesartan, as expected, due to a greater degree of renin-angiotensin-aldosterone system inhibition. Clinicians should monitor for hyperkalemia and renal insufficiency, especially when starting and titrating treatment, Dr. Granger advised.

ORLANDO, FLA. — Men with heart failure and/or bundle branch block are preferentially treated more aggressively with implantable devices than are women with similar health status, a review of nearly 11,000 cases suggests.

The 10,931 patients, of whom 4,138 (38%) were women, were listed in an administrative database and represented consecutive admissions to any of numerous hospitals owned by Hospital Corporation of America. All had a diagnosis of heart failure, bundle branch block, or both, and underwent a primary procedure of pacemaker, cardiac resynchronization therapy pacemaker (CRT-P), implantable cardioverter defibrillator (ICD), or cardiac resynchronization therapy defibrillator (CRT-D) implantation, Robert Fishel, M.D., said at an international conference on women, heart disease, and stroke.

Women received 52% of the pacemakers, 33% of the CRT-Ps, 22% of the ICDs, and 21% of the CRT-Ds implanted, said Dr. Fishel of the J.F.K. Medical Center, Atlantis, Fla. Logistic regression analysis showed that men were significantly less likely than women to receive a pacemaker (odds ratio 0.35) and more likely to receive an ICD (OR 1.34) or CRT-D (OR 1.48). There was no significant difference in device utilization of CRP-Ps between sexes.

After controlling for device, diagnoses, age, and comorbidities, there were no significant differences between men and women in measured clinical outcomes, including mortality, postoperative stroke, postoperative infection, or ICD or pacemaker mechanical malfunction. However, further research is needed to determine if these differences in device use have any long-term effects on outcomes in women, he said.

ORLANDO, FLA. — Men with heart failure and/or bundle branch block are preferentially treated more aggressively with implantable devices than are women with similar health status, a review of nearly 11,000 cases suggests.

The 10,931 patients, of whom 4,138 (38%) were women, were listed in an administrative database and represented consecutive admissions to any of numerous hospitals owned by Hospital Corporation of America. All had a diagnosis of heart failure, bundle branch block, or both, and underwent a primary procedure of pacemaker, cardiac resynchronization therapy pacemaker (CRT-P), implantable cardioverter defibrillator (ICD), or cardiac resynchronization therapy defibrillator (CRT-D) implantation, Robert Fishel, M.D., said at an international conference on women, heart disease, and stroke.

Women received 52% of the pacemakers, 33% of the CRT-Ps, 22% of the ICDs, and 21% of the CRT-Ds implanted, said Dr. Fishel of the J.F.K. Medical Center, Atlantis, Fla. Logistic regression analysis showed that men were significantly less likely than women to receive a pacemaker (odds ratio 0.35) and more likely to receive an ICD (OR 1.34) or CRT-D (OR 1.48). There was no significant difference in device utilization of CRP-Ps between sexes.

After controlling for device, diagnoses, age, and comorbidities, there were no significant differences between men and women in measured clinical outcomes, including mortality, postoperative stroke, postoperative infection, or ICD or pacemaker mechanical malfunction. However, further research is needed to determine if these differences in device use have any long-term effects on outcomes in women, he said.

ORLANDO, FLA. — Men with heart failure and/or bundle branch block are preferentially treated more aggressively with implantable devices than are women with similar health status, a review of nearly 11,000 cases suggests.

The 10,931 patients, of whom 4,138 (38%) were women, were listed in an administrative database and represented consecutive admissions to any of numerous hospitals owned by Hospital Corporation of America. All had a diagnosis of heart failure, bundle branch block, or both, and underwent a primary procedure of pacemaker, cardiac resynchronization therapy pacemaker (CRT-P), implantable cardioverter defibrillator (ICD), or cardiac resynchronization therapy defibrillator (CRT-D) implantation, Robert Fishel, M.D., said at an international conference on women, heart disease, and stroke.

Women received 52% of the pacemakers, 33% of the CRT-Ps, 22% of the ICDs, and 21% of the CRT-Ds implanted, said Dr. Fishel of the J.F.K. Medical Center, Atlantis, Fla. Logistic regression analysis showed that men were significantly less likely than women to receive a pacemaker (odds ratio 0.35) and more likely to receive an ICD (OR 1.34) or CRT-D (OR 1.48). There was no significant difference in device utilization of CRP-Ps between sexes.

After controlling for device, diagnoses, age, and comorbidities, there were no significant differences between men and women in measured clinical outcomes, including mortality, postoperative stroke, postoperative infection, or ICD or pacemaker mechanical malfunction. However, further research is needed to determine if these differences in device use have any long-term effects on outcomes in women, he said.

PHILADELPHIA — Older patients are much less likely to survive their first year on a ventricular assist device than are younger patients, according to a review of 1,365 patients who have received such devices.

But many patients who are at least 60 years old can often benefit from a left ventricular assist device, Peer M. Portner, Ph.D., said at the annual meeting of the International Society for Heart and Lung Transplantation.

“Age is likely a surrogate marker for comorbid conditions at the time of the implant. Left ventricular assist systems [LVAS] can produce a strong survival benefit, even in the oldest patients. This underscores the importance of patient selection for destination therapy,” said Dr. Portner, of the department of cardiothoracic surgery at Stanford University in Palo Alto, Calif., and developer of the Novacor LVAS.

“We have an idea of which patients will do better, but it's been hard to collect the data that could help” identify the patients who will have the best outcomes after receiving an LVAS, he said.

The analysis reported by Dr. Portner came from a registry of patients who received the Novacor LVAS in 1984–2003. During that period, 1,461 patients received the device at 98 centers worldwide. This analysis excluded 70 patients who received the device as destination therapy and 26 patients with inadequate follow-up data, which left 1,365 patients who received the device as a bridge to transplant. The average period of implantation prior to receiving a heart transplant was 144 days for the entire group, but today the average period during which the implant is in place is about 1 year.

Outcomes data were analyzed by the patients' age, and the database was divided into four groups that had similar numbers of patients: those aged 12–39 years (316 patients), aged 40–49 years (353), aged 50–59 years (451), and aged at least 60 years (245).

A logistic regression analysis showed that death during the first year with the device was directly linked to age. Patients in the oldest subgroup (at least 60) had a 2.4-fold increased risk of death compared with all other patients. In contrast, the youngest patients (younger than 40) had a 50% lower risk of death compared with the other patients. The two intermediate age groups had mortality risks between these two extremes.

Expressed another way, the survival rate at 1 year was 75% in patients younger than 40, 70% in those aged 40–49 years, 60% in patients aged 50–59 years, and 40% in those aged at least 60 years. Although mortality was high in older patients, the data also showed that a significant number of older patients could survive beyond 1 year on a LVAS.

“It's unfortunate that we're stuck in the United States with having a separate indication for destination therapy,” said Dr. Portner. “The decision on the ultimate outcome of a recipient of an assist device should depend on how they progress.”

PHILADELPHIA — Older patients are much less likely to survive their first year on a ventricular assist device than are younger patients, according to a review of 1,365 patients who have received such devices.

But many patients who are at least 60 years old can often benefit from a left ventricular assist device, Peer M. Portner, Ph.D., said at the annual meeting of the International Society for Heart and Lung Transplantation.

“Age is likely a surrogate marker for comorbid conditions at the time of the implant. Left ventricular assist systems [LVAS] can produce a strong survival benefit, even in the oldest patients. This underscores the importance of patient selection for destination therapy,” said Dr. Portner, of the department of cardiothoracic surgery at Stanford University in Palo Alto, Calif., and developer of the Novacor LVAS.

“We have an idea of which patients will do better, but it's been hard to collect the data that could help” identify the patients who will have the best outcomes after receiving an LVAS, he said.

The analysis reported by Dr. Portner came from a registry of patients who received the Novacor LVAS in 1984–2003. During that period, 1,461 patients received the device at 98 centers worldwide. This analysis excluded 70 patients who received the device as destination therapy and 26 patients with inadequate follow-up data, which left 1,365 patients who received the device as a bridge to transplant. The average period of implantation prior to receiving a heart transplant was 144 days for the entire group, but today the average period during which the implant is in place is about 1 year.

Outcomes data were analyzed by the patients' age, and the database was divided into four groups that had similar numbers of patients: those aged 12–39 years (316 patients), aged 40–49 years (353), aged 50–59 years (451), and aged at least 60 years (245).

A logistic regression analysis showed that death during the first year with the device was directly linked to age. Patients in the oldest subgroup (at least 60) had a 2.4-fold increased risk of death compared with all other patients. In contrast, the youngest patients (younger than 40) had a 50% lower risk of death compared with the other patients. The two intermediate age groups had mortality risks between these two extremes.

Expressed another way, the survival rate at 1 year was 75% in patients younger than 40, 70% in those aged 40–49 years, 60% in patients aged 50–59 years, and 40% in those aged at least 60 years. Although mortality was high in older patients, the data also showed that a significant number of older patients could survive beyond 1 year on a LVAS.

“It's unfortunate that we're stuck in the United States with having a separate indication for destination therapy,” said Dr. Portner. “The decision on the ultimate outcome of a recipient of an assist device should depend on how they progress.”

PHILADELPHIA — Older patients are much less likely to survive their first year on a ventricular assist device than are younger patients, according to a review of 1,365 patients who have received such devices.

But many patients who are at least 60 years old can often benefit from a left ventricular assist device, Peer M. Portner, Ph.D., said at the annual meeting of the International Society for Heart and Lung Transplantation.

“Age is likely a surrogate marker for comorbid conditions at the time of the implant. Left ventricular assist systems [LVAS] can produce a strong survival benefit, even in the oldest patients. This underscores the importance of patient selection for destination therapy,” said Dr. Portner, of the department of cardiothoracic surgery at Stanford University in Palo Alto, Calif., and developer of the Novacor LVAS.

“We have an idea of which patients will do better, but it's been hard to collect the data that could help” identify the patients who will have the best outcomes after receiving an LVAS, he said.

The analysis reported by Dr. Portner came from a registry of patients who received the Novacor LVAS in 1984–2003. During that period, 1,461 patients received the device at 98 centers worldwide. This analysis excluded 70 patients who received the device as destination therapy and 26 patients with inadequate follow-up data, which left 1,365 patients who received the device as a bridge to transplant. The average period of implantation prior to receiving a heart transplant was 144 days for the entire group, but today the average period during which the implant is in place is about 1 year.

Outcomes data were analyzed by the patients' age, and the database was divided into four groups that had similar numbers of patients: those aged 12–39 years (316 patients), aged 40–49 years (353), aged 50–59 years (451), and aged at least 60 years (245).

A logistic regression analysis showed that death during the first year with the device was directly linked to age. Patients in the oldest subgroup (at least 60) had a 2.4-fold increased risk of death compared with all other patients. In contrast, the youngest patients (younger than 40) had a 50% lower risk of death compared with the other patients. The two intermediate age groups had mortality risks between these two extremes.

Expressed another way, the survival rate at 1 year was 75% in patients younger than 40, 70% in those aged 40–49 years, 60% in patients aged 50–59 years, and 40% in those aged at least 60 years. Although mortality was high in older patients, the data also showed that a significant number of older patients could survive beyond 1 year on a LVAS.

“It's unfortunate that we're stuck in the United States with having a separate indication for destination therapy,” said Dr. Portner. “The decision on the ultimate outcome of a recipient of an assist device should depend on how they progress.”

ORLANDO, FLA. — Using serial plasma B-type natriuretic peptide levels to guide medical therapy in patients with systolic heart failure significantly reduces heart failure-related deaths and hospitalizations, Patrick Jourdain, M.D., said at the annual meeting of the American College of Cardiology.

Half of 220 patients in a 21-center French randomized trial received state-of-the-art, clinically guided medical therapy in accord with practice guidelines. The other half underwent monthly B-type natriuretic peptide (BNP) measurement for 3 months, then three times per year thereafter. The goal in the BNP group was to titrate doses of ACE inhibitors, β-blockers, and diuretics until plasma BNP dropped below 100 pg/mL.

During a median 15 months of follow-up there were three heart failure-related deaths in the BNP group and nine among the clinically managed patients. The primary composite end point in this unsponsored trial—heart failure-related death or hospitalization for heart failure—occurred in 25 patients in the BNP arm and 57 in the control group. This translates to a highly significant 54% reduction in relative risk when BNP was used to optimize medical management, noted Dr. Jourdain of Hôpital Rene Dubos, Pointoise, France.

ORLANDO, FLA. — Using serial plasma B-type natriuretic peptide levels to guide medical therapy in patients with systolic heart failure significantly reduces heart failure-related deaths and hospitalizations, Patrick Jourdain, M.D., said at the annual meeting of the American College of Cardiology.

Half of 220 patients in a 21-center French randomized trial received state-of-the-art, clinically guided medical therapy in accord with practice guidelines. The other half underwent monthly B-type natriuretic peptide (BNP) measurement for 3 months, then three times per year thereafter. The goal in the BNP group was to titrate doses of ACE inhibitors, β-blockers, and diuretics until plasma BNP dropped below 100 pg/mL.

During a median 15 months of follow-up there were three heart failure-related deaths in the BNP group and nine among the clinically managed patients. The primary composite end point in this unsponsored trial—heart failure-related death or hospitalization for heart failure—occurred in 25 patients in the BNP arm and 57 in the control group. This translates to a highly significant 54% reduction in relative risk when BNP was used to optimize medical management, noted Dr. Jourdain of Hôpital Rene Dubos, Pointoise, France.

ORLANDO, FLA. — Using serial plasma B-type natriuretic peptide levels to guide medical therapy in patients with systolic heart failure significantly reduces heart failure-related deaths and hospitalizations, Patrick Jourdain, M.D., said at the annual meeting of the American College of Cardiology.

Half of 220 patients in a 21-center French randomized trial received state-of-the-art, clinically guided medical therapy in accord with practice guidelines. The other half underwent monthly B-type natriuretic peptide (BNP) measurement for 3 months, then three times per year thereafter. The goal in the BNP group was to titrate doses of ACE inhibitors, β-blockers, and diuretics until plasma BNP dropped below 100 pg/mL.

During a median 15 months of follow-up there were three heart failure-related deaths in the BNP group and nine among the clinically managed patients. The primary composite end point in this unsponsored trial—heart failure-related death or hospitalization for heart failure—occurred in 25 patients in the BNP arm and 57 in the control group. This translates to a highly significant 54% reduction in relative risk when BNP was used to optimize medical management, noted Dr. Jourdain of Hôpital Rene Dubos, Pointoise, France.

PHILADELPHIA — The bridge-to-transplant approach for stabilizing patients prior to heart transplantation is working.

Of patients who received a mechanical circulatory support device as a bridge to heart transplant in 2002–2004, half (50%) of those over age 50 and three-quarters (74%) of those under 30 survived to receive a heart transplant during the first year after receiving the device, Marshall I. Hertz, M.D., said at the annual meeting of the International Society for Heart and Lung Transplantation.

“The findings show, in a nonanecdotal way, that you can get a lot of patients to [heart] transplant who otherwise wouldn't get transplanted, said Dr. Hertz, professor of medicine at the University of Minnesota in Minneapolis, and medical director of the International Heart and Lung Transplant Registry.

“The results of several studies have shown that patients who have a heart transplant after receiving a ventricular assist device can do better than patients who are transplanted with no device. It's paradoxical, because the sickest patients get devices, but then they are stabilized and they can get physical rehabilitation and improved nutrition, and they become better candidates for heart transplantation a few months later. The bridging idea started as a last ditch effort for patients, but now it's viewed as interim therapy,” Dr. Hertz said in an interview.

Starting in January 2002, the registry began a voluntary program for submitting case reports for patients who received a mechanical circulatory support device, and as of Dec. 31, 2004, 699 patients were registered. They had received a total of 831 devices at 60 centers worldwide. Follow-up data were available for 655 patients, including 513 who had received a device as a bridge to transplant and 78 patients who received a device as destination therapy. Also, 35 patients received a device as a bridge to recovery, and 29 patients had received a device with an unspecified purpose.

Among all patients who received a device, the actuarial survival rate was 83% after 1 month, 74% after 3 months, 67% after 6 months, and 50% after 1 year.

Survival was linked with age in patients who received a device as a bridge to transplant. Among 292 patients who were aged older than 50 years, mortality was 37% during the first year after they received the device. In contrast, among 52 patients aged younger than 30 years, first-year mortality was 13%, reported Dr. Hertz. A similar analysis was not reported for the remaining 169 patients who were aged 30–50 years.

“The survival to 12 months is not as good as we'd want; additional technical improvements are needed,” said Dr. Hertz.

During 12 months of follow-up of the entire group of 513 patients who received bridge-to-transplant devices, 501 patients had infection episodes, 302 had bleeding episodes, and 75 has thrombotic episodes. The high rate of infection was not surprising, said Dr. Hertz. Infections occur primarily as a consequence of the transcutaneous catheters that devices currently require.

Most of the 78 patients in the registry who received devices as destination therapy were ineligible for heart transplants either because of advanced age (49%) or comorbidity (36%). An additional 10% received a device without listing for a transplant because of fixed pulmonary hypertension.

The long-term prognosis for these patients was not good, especially among older patients. Of the 41 patients in the registry who received destination therapy and were at least 65 years old, 52% died within 6 months of receiving the device, and 74% died within 1 year. Among the 37 patients aged younger than 65 years, 13% died within 6 months and 39% were dead after 1 year.

PHILADELPHIA — The bridge-to-transplant approach for stabilizing patients prior to heart transplantation is working.

Of patients who received a mechanical circulatory support device as a bridge to heart transplant in 2002–2004, half (50%) of those over age 50 and three-quarters (74%) of those under 30 survived to receive a heart transplant during the first year after receiving the device, Marshall I. Hertz, M.D., said at the annual meeting of the International Society for Heart and Lung Transplantation.

“The findings show, in a nonanecdotal way, that you can get a lot of patients to [heart] transplant who otherwise wouldn't get transplanted, said Dr. Hertz, professor of medicine at the University of Minnesota in Minneapolis, and medical director of the International Heart and Lung Transplant Registry.

“The results of several studies have shown that patients who have a heart transplant after receiving a ventricular assist device can do better than patients who are transplanted with no device. It's paradoxical, because the sickest patients get devices, but then they are stabilized and they can get physical rehabilitation and improved nutrition, and they become better candidates for heart transplantation a few months later. The bridging idea started as a last ditch effort for patients, but now it's viewed as interim therapy,” Dr. Hertz said in an interview.

Starting in January 2002, the registry began a voluntary program for submitting case reports for patients who received a mechanical circulatory support device, and as of Dec. 31, 2004, 699 patients were registered. They had received a total of 831 devices at 60 centers worldwide. Follow-up data were available for 655 patients, including 513 who had received a device as a bridge to transplant and 78 patients who received a device as destination therapy. Also, 35 patients received a device as a bridge to recovery, and 29 patients had received a device with an unspecified purpose.

Among all patients who received a device, the actuarial survival rate was 83% after 1 month, 74% after 3 months, 67% after 6 months, and 50% after 1 year.

Survival was linked with age in patients who received a device as a bridge to transplant. Among 292 patients who were aged older than 50 years, mortality was 37% during the first year after they received the device. In contrast, among 52 patients aged younger than 30 years, first-year mortality was 13%, reported Dr. Hertz. A similar analysis was not reported for the remaining 169 patients who were aged 30–50 years.

“The survival to 12 months is not as good as we'd want; additional technical improvements are needed,” said Dr. Hertz.

During 12 months of follow-up of the entire group of 513 patients who received bridge-to-transplant devices, 501 patients had infection episodes, 302 had bleeding episodes, and 75 has thrombotic episodes. The high rate of infection was not surprising, said Dr. Hertz. Infections occur primarily as a consequence of the transcutaneous catheters that devices currently require.

Most of the 78 patients in the registry who received devices as destination therapy were ineligible for heart transplants either because of advanced age (49%) or comorbidity (36%). An additional 10% received a device without listing for a transplant because of fixed pulmonary hypertension.

The long-term prognosis for these patients was not good, especially among older patients. Of the 41 patients in the registry who received destination therapy and were at least 65 years old, 52% died within 6 months of receiving the device, and 74% died within 1 year. Among the 37 patients aged younger than 65 years, 13% died within 6 months and 39% were dead after 1 year.

PHILADELPHIA — The bridge-to-transplant approach for stabilizing patients prior to heart transplantation is working.

Of patients who received a mechanical circulatory support device as a bridge to heart transplant in 2002–2004, half (50%) of those over age 50 and three-quarters (74%) of those under 30 survived to receive a heart transplant during the first year after receiving the device, Marshall I. Hertz, M.D., said at the annual meeting of the International Society for Heart and Lung Transplantation.

“The findings show, in a nonanecdotal way, that you can get a lot of patients to [heart] transplant who otherwise wouldn't get transplanted, said Dr. Hertz, professor of medicine at the University of Minnesota in Minneapolis, and medical director of the International Heart and Lung Transplant Registry.

“The results of several studies have shown that patients who have a heart transplant after receiving a ventricular assist device can do better than patients who are transplanted with no device. It's paradoxical, because the sickest patients get devices, but then they are stabilized and they can get physical rehabilitation and improved nutrition, and they become better candidates for heart transplantation a few months later. The bridging idea started as a last ditch effort for patients, but now it's viewed as interim therapy,” Dr. Hertz said in an interview.

Starting in January 2002, the registry began a voluntary program for submitting case reports for patients who received a mechanical circulatory support device, and as of Dec. 31, 2004, 699 patients were registered. They had received a total of 831 devices at 60 centers worldwide. Follow-up data were available for 655 patients, including 513 who had received a device as a bridge to transplant and 78 patients who received a device as destination therapy. Also, 35 patients received a device as a bridge to recovery, and 29 patients had received a device with an unspecified purpose.

Among all patients who received a device, the actuarial survival rate was 83% after 1 month, 74% after 3 months, 67% after 6 months, and 50% after 1 year.

Survival was linked with age in patients who received a device as a bridge to transplant. Among 292 patients who were aged older than 50 years, mortality was 37% during the first year after they received the device. In contrast, among 52 patients aged younger than 30 years, first-year mortality was 13%, reported Dr. Hertz. A similar analysis was not reported for the remaining 169 patients who were aged 30–50 years.

“The survival to 12 months is not as good as we'd want; additional technical improvements are needed,” said Dr. Hertz.

During 12 months of follow-up of the entire group of 513 patients who received bridge-to-transplant devices, 501 patients had infection episodes, 302 had bleeding episodes, and 75 has thrombotic episodes. The high rate of infection was not surprising, said Dr. Hertz. Infections occur primarily as a consequence of the transcutaneous catheters that devices currently require.

Most of the 78 patients in the registry who received devices as destination therapy were ineligible for heart transplants either because of advanced age (49%) or comorbidity (36%). An additional 10% received a device without listing for a transplant because of fixed pulmonary hypertension.

The long-term prognosis for these patients was not good, especially among older patients. Of the 41 patients in the registry who received destination therapy and were at least 65 years old, 52% died within 6 months of receiving the device, and 74% died within 1 year. Among the 37 patients aged younger than 65 years, 13% died within 6 months and 39% were dead after 1 year.

ORLANDO, FLA. — Statin therapy may markedly improve survival in patients with advanced heart failure, regardless of whether the etiology is ischemic or nonischemic, Andrew D. Sumner, M.D., said at the annual meeting of the American College of Cardiology.

This enhanced survival appears to be due primarily to a reduced incidence of arrhythmic death, added Dr. Sumner of Pennsylvania State University, Hershey.

He presented a retrospective analysis of data from the previously reported prospective Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION) trial. In COMPANION, 1,520 patients with advanced heart failure (HF) at 128 U.S. centers were randomized 1:2:2 to optimal drug therapy alone, in conjunction with a cardiac resynchronization pacemaker, or with a combined cardiac resynchronization pacemaker/implantable cardioverter defibrillator (ICD).

There were 313 deaths during a median 16 months of follow-up. Unadjusted all-cause mortality among the 40% of COMPANION participants on a statin was 18%, compared with 22% in those who weren't on a statin. After controlling for numerous variables—including New York Heart Association class, left ventricular ejection fraction, QRS duration, blood pressure, gender, age, diabetes and other comorbidities, HF duration and etiology, and treatment assignment—statin use was associated with a highly significant 28% reduction in all-cause mortality.

A closer look at the data showed that statin use was associated with an adjusted 33% reduction in all-cause mortality among patients randomized to device therapy, but with no gain in survival in patients who received only optimal pharmacologic therapy. Further analysis showed that statin-treated patients on cardiac resynchronization therapy without an ICD had a 46% relative risk reduction in all-cause mortality and a 63% reduction in sudden cardiac death, compared with those not on a statin.

In contrast, statin therapy did not appear to have any effect upon all-cause mortality or sudden cardiac death in patients on cardiac resynchronization therapy plus an ICD. This is to be expected, since the ICD already protects against sudden cardiac death, which together with pump failure constitute the two chief causes of mortality in patients with advanced HF.

Dr. Sumner stressed that COMPANION participants were not randomized to statin therapy, and as a retrospective analysis, his study must be considered hypothesis generating. “Hopefully, there will be a randomized, placebo-controlled trial to confirm these observations,” he added.

Although statins are best known for their potent LDL-lowering effect, they have a number of other actions believed to be important in preventing cardiovascular events. The drugs reduce markers of inflammation, normalize endothelial dysfunction, and improve production of nitric oxide.

“Because heart failure is characterized by decreased cardiac performance, with activation of neurohormones, release of proinflammatory cytokines, and abnormalities in nitric oxide biosynthesis, treating patients with chronic heart failure with statins is potentially attractive,” the cardiologist observed.

Several prior studies support the notion of statins having an antiarrhythmic effect that could spell reduced risk of sudden cardiac death in patients with advanced HF. For example, statin users have been reported to have a reduced risk of developing atrial fibrillation, and statin therapy favorably affects defibrillation thresholds in animal studies of ischemic heart disease. There are also data showing statins exert beneficial effects upon norepinephrine levels and sympathetic nervous system activity, which is also consistent with statins lowering the risk of arrhythmic death, Dr. Sumner said.

ORLANDO, FLA. — Statin therapy may markedly improve survival in patients with advanced heart failure, regardless of whether the etiology is ischemic or nonischemic, Andrew D. Sumner, M.D., said at the annual meeting of the American College of Cardiology.

This enhanced survival appears to be due primarily to a reduced incidence of arrhythmic death, added Dr. Sumner of Pennsylvania State University, Hershey.

He presented a retrospective analysis of data from the previously reported prospective Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION) trial. In COMPANION, 1,520 patients with advanced heart failure (HF) at 128 U.S. centers were randomized 1:2:2 to optimal drug therapy alone, in conjunction with a cardiac resynchronization pacemaker, or with a combined cardiac resynchronization pacemaker/implantable cardioverter defibrillator (ICD).

There were 313 deaths during a median 16 months of follow-up. Unadjusted all-cause mortality among the 40% of COMPANION participants on a statin was 18%, compared with 22% in those who weren't on a statin. After controlling for numerous variables—including New York Heart Association class, left ventricular ejection fraction, QRS duration, blood pressure, gender, age, diabetes and other comorbidities, HF duration and etiology, and treatment assignment—statin use was associated with a highly significant 28% reduction in all-cause mortality.

A closer look at the data showed that statin use was associated with an adjusted 33% reduction in all-cause mortality among patients randomized to device therapy, but with no gain in survival in patients who received only optimal pharmacologic therapy. Further analysis showed that statin-treated patients on cardiac resynchronization therapy without an ICD had a 46% relative risk reduction in all-cause mortality and a 63% reduction in sudden cardiac death, compared with those not on a statin.

In contrast, statin therapy did not appear to have any effect upon all-cause mortality or sudden cardiac death in patients on cardiac resynchronization therapy plus an ICD. This is to be expected, since the ICD already protects against sudden cardiac death, which together with pump failure constitute the two chief causes of mortality in patients with advanced HF.

Dr. Sumner stressed that COMPANION participants were not randomized to statin therapy, and as a retrospective analysis, his study must be considered hypothesis generating. “Hopefully, there will be a randomized, placebo-controlled trial to confirm these observations,” he added.

Although statins are best known for their potent LDL-lowering effect, they have a number of other actions believed to be important in preventing cardiovascular events. The drugs reduce markers of inflammation, normalize endothelial dysfunction, and improve production of nitric oxide.

“Because heart failure is characterized by decreased cardiac performance, with activation of neurohormones, release of proinflammatory cytokines, and abnormalities in nitric oxide biosynthesis, treating patients with chronic heart failure with statins is potentially attractive,” the cardiologist observed.

Several prior studies support the notion of statins having an antiarrhythmic effect that could spell reduced risk of sudden cardiac death in patients with advanced HF. For example, statin users have been reported to have a reduced risk of developing atrial fibrillation, and statin therapy favorably affects defibrillation thresholds in animal studies of ischemic heart disease. There are also data showing statins exert beneficial effects upon norepinephrine levels and sympathetic nervous system activity, which is also consistent with statins lowering the risk of arrhythmic death, Dr. Sumner said.

ORLANDO, FLA. — Statin therapy may markedly improve survival in patients with advanced heart failure, regardless of whether the etiology is ischemic or nonischemic, Andrew D. Sumner, M.D., said at the annual meeting of the American College of Cardiology.

This enhanced survival appears to be due primarily to a reduced incidence of arrhythmic death, added Dr. Sumner of Pennsylvania State University, Hershey.

He presented a retrospective analysis of data from the previously reported prospective Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION) trial. In COMPANION, 1,520 patients with advanced heart failure (HF) at 128 U.S. centers were randomized 1:2:2 to optimal drug therapy alone, in conjunction with a cardiac resynchronization pacemaker, or with a combined cardiac resynchronization pacemaker/implantable cardioverter defibrillator (ICD).

There were 313 deaths during a median 16 months of follow-up. Unadjusted all-cause mortality among the 40% of COMPANION participants on a statin was 18%, compared with 22% in those who weren't on a statin. After controlling for numerous variables—including New York Heart Association class, left ventricular ejection fraction, QRS duration, blood pressure, gender, age, diabetes and other comorbidities, HF duration and etiology, and treatment assignment—statin use was associated with a highly significant 28% reduction in all-cause mortality.

A closer look at the data showed that statin use was associated with an adjusted 33% reduction in all-cause mortality among patients randomized to device therapy, but with no gain in survival in patients who received only optimal pharmacologic therapy. Further analysis showed that statin-treated patients on cardiac resynchronization therapy without an ICD had a 46% relative risk reduction in all-cause mortality and a 63% reduction in sudden cardiac death, compared with those not on a statin.

In contrast, statin therapy did not appear to have any effect upon all-cause mortality or sudden cardiac death in patients on cardiac resynchronization therapy plus an ICD. This is to be expected, since the ICD already protects against sudden cardiac death, which together with pump failure constitute the two chief causes of mortality in patients with advanced HF.

Dr. Sumner stressed that COMPANION participants were not randomized to statin therapy, and as a retrospective analysis, his study must be considered hypothesis generating. “Hopefully, there will be a randomized, placebo-controlled trial to confirm these observations,” he added.

Although statins are best known for their potent LDL-lowering effect, they have a number of other actions believed to be important in preventing cardiovascular events. The drugs reduce markers of inflammation, normalize endothelial dysfunction, and improve production of nitric oxide.

“Because heart failure is characterized by decreased cardiac performance, with activation of neurohormones, release of proinflammatory cytokines, and abnormalities in nitric oxide biosynthesis, treating patients with chronic heart failure with statins is potentially attractive,” the cardiologist observed.

Several prior studies support the notion of statins having an antiarrhythmic effect that could spell reduced risk of sudden cardiac death in patients with advanced HF. For example, statin users have been reported to have a reduced risk of developing atrial fibrillation, and statin therapy favorably affects defibrillation thresholds in animal studies of ischemic heart disease. There are also data showing statins exert beneficial effects upon norepinephrine levels and sympathetic nervous system activity, which is also consistent with statins lowering the risk of arrhythmic death, Dr. Sumner said.

PHILADELPHIA — Implantation of a left ventricular assist device in patients with a relative contraindication for heart transplantation can buy patients time for the rehabilitation therapy they need to become eligible to receive an organ.

Using an assist device this way has been dubbed “bridge to eligibility.”

In a subgroup analysis of 87 patients who received a Novacor left ventricular assist system (LVAS) when they were clinically ineligible for a heart transplant because of a relative contraindication, about two-thirds subsequently improved sufficiently on the device to become eligible for listing and went on to receive a transplanted heart, James B. Young, M.D., reported at the annual meeting of the International Society for Heart and Lung Transplantation.

In contrast, in a control group of 12 patients who did not receive the LVAS, only a third of the patients subsequently became eligible for a heart transplant, reported Dr. Young, chairman of the division of medicine at the Cleveland Clinic Foundation.

These findings came from a study that was sponsored by WorldHeart, which makes the Novacor device.

Although bridge to eligibility works clinically, the Food and Drug Administration has yet to approve it as a formal indication for an LVAS. In June 2004, the FDA reviewed the same data that Dr. Young reported at the meeting and rejected a proposal from WorldHeart to change the wording of the device's approved indications. The LVAS could continue to be used as a bridge to transplant or as destination therapy, but not as a bridge to eligibility.

Dr. Young took issue with this decision.

“The indication for these devices should be for carefully selected and appropriate patients with end-stage heart failure, with absolutely no tie to whether it will be as a bridge to transplant, bridge to eligibility, or destination therapy,” he said. “We should recognize the robust data that we have that says that we can rehabilitate many patients. We need to plumb the concept of using LVAS for ill patients and then deciding which direction to take the patient.”

By not having an approved indication of bridge to eligibility, some insurers have refused to cover the cost of placing an LVAS in a patient who has relative contraindications for a heart transplant at the time of treatment, Dr. Young said.

According to formal definitions, any patient listed as a transplant candidate should be ready to receive a donor heart as soon as it's available. The reality is that “many patients get LVAS and are said to be transplant candidates even if they have relative contraindications because it's reasonable to expect some contraindications to dissipate while the patient is on an LVAS,” said Dr. Young.

The most common contraindications that can potentially resolve with LVAS treatment are renal insufficiency, pulmonary hypertension, hepatic dysfunction, and obesity.

The data that Dr. Young reported came from the 225-patient pivotal trial for Novacor; 190 of these patients were randomized to receive an LVAS, and the remaining 35 patients served as control subjects.

Among the 225 patients, 87 had relative contraindications for heart transplant at the time they entered the study. LVAS treatment was used on 75 of these patients; the other 12 served as controls.

During the study, 49 of the 75 patients with an LVAS (65%) improved so that they could receive a heart transplant, compared with 4 of 12 patients in the control group (33%).

In addition, following heart transplantation, the rate of survival was similar among the patients who initially had contraindications and those who did not, showing that the patients can have successful transplant outcomes when managed as bridge-to-eligibility patients, Dr. Young said.

PHILADELPHIA — Implantation of a left ventricular assist device in patients with a relative contraindication for heart transplantation can buy patients time for the rehabilitation therapy they need to become eligible to receive an organ.

Using an assist device this way has been dubbed “bridge to eligibility.”

In a subgroup analysis of 87 patients who received a Novacor left ventricular assist system (LVAS) when they were clinically ineligible for a heart transplant because of a relative contraindication, about two-thirds subsequently improved sufficiently on the device to become eligible for listing and went on to receive a transplanted heart, James B. Young, M.D., reported at the annual meeting of the International Society for Heart and Lung Transplantation.

In contrast, in a control group of 12 patients who did not receive the LVAS, only a third of the patients subsequently became eligible for a heart transplant, reported Dr. Young, chairman of the division of medicine at the Cleveland Clinic Foundation.

These findings came from a study that was sponsored by WorldHeart, which makes the Novacor device.

Although bridge to eligibility works clinically, the Food and Drug Administration has yet to approve it as a formal indication for an LVAS. In June 2004, the FDA reviewed the same data that Dr. Young reported at the meeting and rejected a proposal from WorldHeart to change the wording of the device's approved indications. The LVAS could continue to be used as a bridge to transplant or as destination therapy, but not as a bridge to eligibility.

Dr. Young took issue with this decision.

“The indication for these devices should be for carefully selected and appropriate patients with end-stage heart failure, with absolutely no tie to whether it will be as a bridge to transplant, bridge to eligibility, or destination therapy,” he said. “We should recognize the robust data that we have that says that we can rehabilitate many patients. We need to plumb the concept of using LVAS for ill patients and then deciding which direction to take the patient.”

By not having an approved indication of bridge to eligibility, some insurers have refused to cover the cost of placing an LVAS in a patient who has relative contraindications for a heart transplant at the time of treatment, Dr. Young said.

According to formal definitions, any patient listed as a transplant candidate should be ready to receive a donor heart as soon as it's available. The reality is that “many patients get LVAS and are said to be transplant candidates even if they have relative contraindications because it's reasonable to expect some contraindications to dissipate while the patient is on an LVAS,” said Dr. Young.

The most common contraindications that can potentially resolve with LVAS treatment are renal insufficiency, pulmonary hypertension, hepatic dysfunction, and obesity.

The data that Dr. Young reported came from the 225-patient pivotal trial for Novacor; 190 of these patients were randomized to receive an LVAS, and the remaining 35 patients served as control subjects.

Among the 225 patients, 87 had relative contraindications for heart transplant at the time they entered the study. LVAS treatment was used on 75 of these patients; the other 12 served as controls.

During the study, 49 of the 75 patients with an LVAS (65%) improved so that they could receive a heart transplant, compared with 4 of 12 patients in the control group (33%).

In addition, following heart transplantation, the rate of survival was similar among the patients who initially had contraindications and those who did not, showing that the patients can have successful transplant outcomes when managed as bridge-to-eligibility patients, Dr. Young said.

PHILADELPHIA — Implantation of a left ventricular assist device in patients with a relative contraindication for heart transplantation can buy patients time for the rehabilitation therapy they need to become eligible to receive an organ.

Using an assist device this way has been dubbed “bridge to eligibility.”

In a subgroup analysis of 87 patients who received a Novacor left ventricular assist system (LVAS) when they were clinically ineligible for a heart transplant because of a relative contraindication, about two-thirds subsequently improved sufficiently on the device to become eligible for listing and went on to receive a transplanted heart, James B. Young, M.D., reported at the annual meeting of the International Society for Heart and Lung Transplantation.

In contrast, in a control group of 12 patients who did not receive the LVAS, only a third of the patients subsequently became eligible for a heart transplant, reported Dr. Young, chairman of the division of medicine at the Cleveland Clinic Foundation.

These findings came from a study that was sponsored by WorldHeart, which makes the Novacor device.

Although bridge to eligibility works clinically, the Food and Drug Administration has yet to approve it as a formal indication for an LVAS. In June 2004, the FDA reviewed the same data that Dr. Young reported at the meeting and rejected a proposal from WorldHeart to change the wording of the device's approved indications. The LVAS could continue to be used as a bridge to transplant or as destination therapy, but not as a bridge to eligibility.

Dr. Young took issue with this decision.

“The indication for these devices should be for carefully selected and appropriate patients with end-stage heart failure, with absolutely no tie to whether it will be as a bridge to transplant, bridge to eligibility, or destination therapy,” he said. “We should recognize the robust data that we have that says that we can rehabilitate many patients. We need to plumb the concept of using LVAS for ill patients and then deciding which direction to take the patient.”

By not having an approved indication of bridge to eligibility, some insurers have refused to cover the cost of placing an LVAS in a patient who has relative contraindications for a heart transplant at the time of treatment, Dr. Young said.

According to formal definitions, any patient listed as a transplant candidate should be ready to receive a donor heart as soon as it's available. The reality is that “many patients get LVAS and are said to be transplant candidates even if they have relative contraindications because it's reasonable to expect some contraindications to dissipate while the patient is on an LVAS,” said Dr. Young.

The most common contraindications that can potentially resolve with LVAS treatment are renal insufficiency, pulmonary hypertension, hepatic dysfunction, and obesity.

The data that Dr. Young reported came from the 225-patient pivotal trial for Novacor; 190 of these patients were randomized to receive an LVAS, and the remaining 35 patients served as control subjects.

Among the 225 patients, 87 had relative contraindications for heart transplant at the time they entered the study. LVAS treatment was used on 75 of these patients; the other 12 served as controls.

During the study, 49 of the 75 patients with an LVAS (65%) improved so that they could receive a heart transplant, compared with 4 of 12 patients in the control group (33%).

In addition, following heart transplantation, the rate of survival was similar among the patients who initially had contraindications and those who did not, showing that the patients can have successful transplant outcomes when managed as bridge-to-eligibility patients, Dr. Young said.