Heart Failure

SAN FRANCISCO — Maternal peripartum cardiomyopathy, seen in 1 in 3,000 live births, generally carries a good prognosis, Dr. Michael Crawford said at a meeting sponsored by the California chapter of the American College of Cardiology.

Diagnosis of peripartum cardiomyopathy—or of other heart diseases during pregnancy—often is delayed because the symptoms of pregnancy are alike, said Dr. Crawford, professor of medicine at the University of California, San Francisco.

A majority of women with peripartum cardiomyopathy recover after delivery, but 10%–20% require heart transplantation and 1%–2% die, data suggest. The patient's ejection fraction 2 months after diagnosis appears to be the best prognostic factor, he said at the meeting, also sponsored by the university.

Treatment differs for pregnant women compared with nonpregnant patients because some drugs shouldn't be used until after delivery. ACE inhibitors and warfarin are teratogenic, and β-blockers can lead to fetal bradycardia. “You get by with diuretics, digoxin, and hydralazine during pregnancy,” Dr. Crawford said.

In a recent study at a large medical center, ejection fractions improved at least 15% in 62% of women with peripartum cardiomyopathy, remained unchanged in 25%, and declined in 13% (Am. Heart J. 2006;152:509–13).

Ejection fractions returned to normal in 45%. Ten percent of patients required transplantation. No patients died during an average 43-month follow-up. The initial echocardiogram, obtained between 1 month prepartum and 5 months post partum, did not predict which patients required transplantation, nor which had final ejection fractions below or above 50%. “Don't get discouraged with the first echo,” Dr. Crawford said. Echocardiograms 2 months later predicted outcomes in that study.

Patients with ejection fractions below 20% probably are headed for transplant. Those with ejection fractions between 20% and 50% should see some improvement but are unlikely to return to normal. If the 2-month ejection fraction is above 40%, the patient is likely to recover fully (defined as an ejection fraction greater than 50%), he said.

Shortness of breath and decreased exercise capacity—symptoms of cardiomyopathy—also are symptoms of a normal pregnancy. Fatigue, orthopnea, and dizziness or syncope, which might be symptoms of other heart disease, can also be caused by pregnancy.

Electrocardiograms in normal pregnancies often detect sinus tachycardia, and may show nonspecific ST-T changes. As the pregnancy advances, the heart's axis shifts more to the left. Physical findings in normal pregnancies may include jugular venous distention, an enlarged left ventricle apex, right ventricle heave, a palpable pulmonary artery pulse, third heart sounds, systolic ejection murmurs, venous hums, or a mammary souffle noise if you listen over the breast.

The most common peripartum cardiovascular problem is venous thromboembolism, which is the leading cause of death in pregnancy, he added. Consider prophylactic medication in women with risk factors.

Coronary artery disease during pregnancy is more common than one might think, perhaps because more women are having children later in life, he added. Maternal MI occurs in 6 out of 100,000 deliveries, three to four times more common than is expected in age-matched nonpregnant women.

Elevated troponin levels are abnormal in pregnancy, and are a red flag. Thrombolytics can be used without causing a lot of fetal complications. Around 5% of women with peripartum MI die.

SAN FRANCISCO — Maternal peripartum cardiomyopathy, seen in 1 in 3,000 live births, generally carries a good prognosis, Dr. Michael Crawford said at a meeting sponsored by the California chapter of the American College of Cardiology.

Diagnosis of peripartum cardiomyopathy—or of other heart diseases during pregnancy—often is delayed because the symptoms of pregnancy are alike, said Dr. Crawford, professor of medicine at the University of California, San Francisco.

A majority of women with peripartum cardiomyopathy recover after delivery, but 10%–20% require heart transplantation and 1%–2% die, data suggest. The patient's ejection fraction 2 months after diagnosis appears to be the best prognostic factor, he said at the meeting, also sponsored by the university.

Treatment differs for pregnant women compared with nonpregnant patients because some drugs shouldn't be used until after delivery. ACE inhibitors and warfarin are teratogenic, and β-blockers can lead to fetal bradycardia. “You get by with diuretics, digoxin, and hydralazine during pregnancy,” Dr. Crawford said.

In a recent study at a large medical center, ejection fractions improved at least 15% in 62% of women with peripartum cardiomyopathy, remained unchanged in 25%, and declined in 13% (Am. Heart J. 2006;152:509–13).

Ejection fractions returned to normal in 45%. Ten percent of patients required transplantation. No patients died during an average 43-month follow-up. The initial echocardiogram, obtained between 1 month prepartum and 5 months post partum, did not predict which patients required transplantation, nor which had final ejection fractions below or above 50%. “Don't get discouraged with the first echo,” Dr. Crawford said. Echocardiograms 2 months later predicted outcomes in that study.

Patients with ejection fractions below 20% probably are headed for transplant. Those with ejection fractions between 20% and 50% should see some improvement but are unlikely to return to normal. If the 2-month ejection fraction is above 40%, the patient is likely to recover fully (defined as an ejection fraction greater than 50%), he said.

Shortness of breath and decreased exercise capacity—symptoms of cardiomyopathy—also are symptoms of a normal pregnancy. Fatigue, orthopnea, and dizziness or syncope, which might be symptoms of other heart disease, can also be caused by pregnancy.

Electrocardiograms in normal pregnancies often detect sinus tachycardia, and may show nonspecific ST-T changes. As the pregnancy advances, the heart's axis shifts more to the left. Physical findings in normal pregnancies may include jugular venous distention, an enlarged left ventricle apex, right ventricle heave, a palpable pulmonary artery pulse, third heart sounds, systolic ejection murmurs, venous hums, or a mammary souffle noise if you listen over the breast.

The most common peripartum cardiovascular problem is venous thromboembolism, which is the leading cause of death in pregnancy, he added. Consider prophylactic medication in women with risk factors.

Coronary artery disease during pregnancy is more common than one might think, perhaps because more women are having children later in life, he added. Maternal MI occurs in 6 out of 100,000 deliveries, three to four times more common than is expected in age-matched nonpregnant women.

Elevated troponin levels are abnormal in pregnancy, and are a red flag. Thrombolytics can be used without causing a lot of fetal complications. Around 5% of women with peripartum MI die.

SAN FRANCISCO — Maternal peripartum cardiomyopathy, seen in 1 in 3,000 live births, generally carries a good prognosis, Dr. Michael Crawford said at a meeting sponsored by the California chapter of the American College of Cardiology.

Diagnosis of peripartum cardiomyopathy—or of other heart diseases during pregnancy—often is delayed because the symptoms of pregnancy are alike, said Dr. Crawford, professor of medicine at the University of California, San Francisco.

A majority of women with peripartum cardiomyopathy recover after delivery, but 10%–20% require heart transplantation and 1%–2% die, data suggest. The patient's ejection fraction 2 months after diagnosis appears to be the best prognostic factor, he said at the meeting, also sponsored by the university.

Treatment differs for pregnant women compared with nonpregnant patients because some drugs shouldn't be used until after delivery. ACE inhibitors and warfarin are teratogenic, and β-blockers can lead to fetal bradycardia. “You get by with diuretics, digoxin, and hydralazine during pregnancy,” Dr. Crawford said.

In a recent study at a large medical center, ejection fractions improved at least 15% in 62% of women with peripartum cardiomyopathy, remained unchanged in 25%, and declined in 13% (Am. Heart J. 2006;152:509–13).

Ejection fractions returned to normal in 45%. Ten percent of patients required transplantation. No patients died during an average 43-month follow-up. The initial echocardiogram, obtained between 1 month prepartum and 5 months post partum, did not predict which patients required transplantation, nor which had final ejection fractions below or above 50%. “Don't get discouraged with the first echo,” Dr. Crawford said. Echocardiograms 2 months later predicted outcomes in that study.

Patients with ejection fractions below 20% probably are headed for transplant. Those with ejection fractions between 20% and 50% should see some improvement but are unlikely to return to normal. If the 2-month ejection fraction is above 40%, the patient is likely to recover fully (defined as an ejection fraction greater than 50%), he said.

Shortness of breath and decreased exercise capacity—symptoms of cardiomyopathy—also are symptoms of a normal pregnancy. Fatigue, orthopnea, and dizziness or syncope, which might be symptoms of other heart disease, can also be caused by pregnancy.

Electrocardiograms in normal pregnancies often detect sinus tachycardia, and may show nonspecific ST-T changes. As the pregnancy advances, the heart's axis shifts more to the left. Physical findings in normal pregnancies may include jugular venous distention, an enlarged left ventricle apex, right ventricle heave, a palpable pulmonary artery pulse, third heart sounds, systolic ejection murmurs, venous hums, or a mammary souffle noise if you listen over the breast.

The most common peripartum cardiovascular problem is venous thromboembolism, which is the leading cause of death in pregnancy, he added. Consider prophylactic medication in women with risk factors.

Coronary artery disease during pregnancy is more common than one might think, perhaps because more women are having children later in life, he added. Maternal MI occurs in 6 out of 100,000 deliveries, three to four times more common than is expected in age-matched nonpregnant women.

Elevated troponin levels are abnormal in pregnancy, and are a red flag. Thrombolytics can be used without causing a lot of fetal complications. Around 5% of women with peripartum MI die.

ORLANDO — Regularly eating a bowl of whole-grain cereal was linked to a significant drop in the risk for heart failure in a study with more than 20,000 men.

“It's not just breakfast cereal, but the whole-grain concept, including whole-grain bread, pasta, and rice,” Dr. Luc Djoussé said at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

Regular consumption of whole-grain cereal probably cuts the risk for heart failure by supplying fiber, nutrients, and phytoestrogens, added Dr. Djoussé, who is a physician and epidemiologist at Harvard University and Brigham and Women's Hospital in Boston. He added that he believes the study to be the first of its kind.

The study used data collected prospectively from 21,410 men who participated in the Physicians' Health Study. Their average age at entry was 54 years (range, 40–86 years). The analysis excluded men with heart failure at the study's start, and those who failed to provide data on their consumption of breakfast cereal. Diet data were collected regularly during up to 24 years of follow-up. Whole-grain breakfast cereal was defined as a formulation that contained at least 25% oats or bran.

Over an average follow-up of 19.6 years, 1,018 men developed heart failure. The risk of heart failure was correlated with the frequency of eating whole-grain breakfast cereal. The men were divided into four categories of consumption: none (33%); one or fewer servings per week but more than none (23%); two to six servings per week (24%); and seven or more servings per week (19%). (The total is less than 100% because of rounding.)

In an analysis that controlled for baseline levels of potential confounders—including age, body mass index, smoking history, alcohol use, multivitamin use, diabetes, hypertension, and valvular heart disease—men who ate seven or more servings of whole-grain cereal a week had about a 30% reduced risk of developing heart failure, compared with men who did not eat whole-grain cereal. Men who ate two to six servings a week had about a 20% reduced risk. Both of these differences were statistically significant. No significant change was seen in men who ate one serving a week or less, and no link was seen between the consumption of refined breakfast cereals and heart failure risk.

The study did not receive any commercial funding.

ORLANDO — Regularly eating a bowl of whole-grain cereal was linked to a significant drop in the risk for heart failure in a study with more than 20,000 men.

“It's not just breakfast cereal, but the whole-grain concept, including whole-grain bread, pasta, and rice,” Dr. Luc Djoussé said at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

Regular consumption of whole-grain cereal probably cuts the risk for heart failure by supplying fiber, nutrients, and phytoestrogens, added Dr. Djoussé, who is a physician and epidemiologist at Harvard University and Brigham and Women's Hospital in Boston. He added that he believes the study to be the first of its kind.

The study used data collected prospectively from 21,410 men who participated in the Physicians' Health Study. Their average age at entry was 54 years (range, 40–86 years). The analysis excluded men with heart failure at the study's start, and those who failed to provide data on their consumption of breakfast cereal. Diet data were collected regularly during up to 24 years of follow-up. Whole-grain breakfast cereal was defined as a formulation that contained at least 25% oats or bran.

Over an average follow-up of 19.6 years, 1,018 men developed heart failure. The risk of heart failure was correlated with the frequency of eating whole-grain breakfast cereal. The men were divided into four categories of consumption: none (33%); one or fewer servings per week but more than none (23%); two to six servings per week (24%); and seven or more servings per week (19%). (The total is less than 100% because of rounding.)

In an analysis that controlled for baseline levels of potential confounders—including age, body mass index, smoking history, alcohol use, multivitamin use, diabetes, hypertension, and valvular heart disease—men who ate seven or more servings of whole-grain cereal a week had about a 30% reduced risk of developing heart failure, compared with men who did not eat whole-grain cereal. Men who ate two to six servings a week had about a 20% reduced risk. Both of these differences were statistically significant. No significant change was seen in men who ate one serving a week or less, and no link was seen between the consumption of refined breakfast cereals and heart failure risk.

The study did not receive any commercial funding.

ORLANDO — Regularly eating a bowl of whole-grain cereal was linked to a significant drop in the risk for heart failure in a study with more than 20,000 men.

“It's not just breakfast cereal, but the whole-grain concept, including whole-grain bread, pasta, and rice,” Dr. Luc Djoussé said at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

Regular consumption of whole-grain cereal probably cuts the risk for heart failure by supplying fiber, nutrients, and phytoestrogens, added Dr. Djoussé, who is a physician and epidemiologist at Harvard University and Brigham and Women's Hospital in Boston. He added that he believes the study to be the first of its kind.

The study used data collected prospectively from 21,410 men who participated in the Physicians' Health Study. Their average age at entry was 54 years (range, 40–86 years). The analysis excluded men with heart failure at the study's start, and those who failed to provide data on their consumption of breakfast cereal. Diet data were collected regularly during up to 24 years of follow-up. Whole-grain breakfast cereal was defined as a formulation that contained at least 25% oats or bran.

Over an average follow-up of 19.6 years, 1,018 men developed heart failure. The risk of heart failure was correlated with the frequency of eating whole-grain breakfast cereal. The men were divided into four categories of consumption: none (33%); one or fewer servings per week but more than none (23%); two to six servings per week (24%); and seven or more servings per week (19%). (The total is less than 100% because of rounding.)

In an analysis that controlled for baseline levels of potential confounders—including age, body mass index, smoking history, alcohol use, multivitamin use, diabetes, hypertension, and valvular heart disease—men who ate seven or more servings of whole-grain cereal a week had about a 30% reduced risk of developing heart failure, compared with men who did not eat whole-grain cereal. Men who ate two to six servings a week had about a 20% reduced risk. Both of these differences were statistically significant. No significant change was seen in men who ate one serving a week or less, and no link was seen between the consumption of refined breakfast cereals and heart failure risk.

The study did not receive any commercial funding.

CARMEL, CALIF. — B-type natriuretic peptide levels are not effective in detecting clinically relevant heart failure following heart transplantation, results from a study of 130 patients showed.

The finding is important because while the role of B-type natriuretic peptide (BNP) levels in detecting symptomatic heart failure in nontransplanted patients has been well established, its role in patients who have undergone heart transplantation is unclear.

“What we do know is that BNP is elevated right after [heart] transplant,” Meghana Yajnik said during a poster presentation at the Western regional meeting of the American Federation for Medical Research.

“However, several recent studies have said that BNP may have potential as a prognostic marker, in which high levels of BNP for prolonged periods after transplant may portend poorer outcome,” she noted

Ms. Yajnik, who is a second-year undergraduate student at University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 130 consecutive patients who received heart transplants at the university between July 2001 and November 2003. All of the patients had BNP levels assessed at the time of their right heart catheterization and their clinical exams.

The researchers defined heart failure as both the presence of symptoms (including dyspnea, edema, or a documented increase in diuretic dose), and a pulmonary capillary wedge pressure of 15 mm Hg or greater. BNP samples taken during the first 3 months post transplant and those taken in patients with renal insufficiency (defined as a creatinine level of greater than 1.9 mg/dL) were excluded from the analysis. The mean follow-up time was 28 months.

Of the 130 patients, 67 had 124 BNP measurements with a pulmonary capillary wedge pressure of at least 15 mm Hg. Ms. Yajnik reported that the BNP level was at least 150 pg/mL in 42 of the 124 measurements (39%). In 29 patients who had symptomatic heart failure and a pulmonary capillary wedge pressure of at least 15 mm Hg, the BNP level was at least 150 pg/mL in only 19 of the 42 measurements (45%).

“Therefore,” the researchers wrote in their abstract, “a BNP level of 150 pg/mL or greater was found to have a sensitivity of only 45.2%, a specificity of 64.9%, a positive predictive value of 3.7%, and a negative predictive value of 2.4% for the detection of heart failure in heart transplant recipients. In addition, a BNP value of 150 pg/mL or greater within 8 weeks of a clinically significant episode of rejection was noted in only 5 of 10 cases.”

Ms. Yajnik noted that the discrepancy between the use of B-type natriuretic peptide levels for detecting heart failure in the nontransplant and transplant populations requires further study. “Differences in the physiology between nontransplant patients and transplant patients may account for these disparate BNP levels,” she said.

CARMEL, CALIF. — B-type natriuretic peptide levels are not effective in detecting clinically relevant heart failure following heart transplantation, results from a study of 130 patients showed.

The finding is important because while the role of B-type natriuretic peptide (BNP) levels in detecting symptomatic heart failure in nontransplanted patients has been well established, its role in patients who have undergone heart transplantation is unclear.

“What we do know is that BNP is elevated right after [heart] transplant,” Meghana Yajnik said during a poster presentation at the Western regional meeting of the American Federation for Medical Research.

“However, several recent studies have said that BNP may have potential as a prognostic marker, in which high levels of BNP for prolonged periods after transplant may portend poorer outcome,” she noted

Ms. Yajnik, who is a second-year undergraduate student at University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 130 consecutive patients who received heart transplants at the university between July 2001 and November 2003. All of the patients had BNP levels assessed at the time of their right heart catheterization and their clinical exams.

The researchers defined heart failure as both the presence of symptoms (including dyspnea, edema, or a documented increase in diuretic dose), and a pulmonary capillary wedge pressure of 15 mm Hg or greater. BNP samples taken during the first 3 months post transplant and those taken in patients with renal insufficiency (defined as a creatinine level of greater than 1.9 mg/dL) were excluded from the analysis. The mean follow-up time was 28 months.

Of the 130 patients, 67 had 124 BNP measurements with a pulmonary capillary wedge pressure of at least 15 mm Hg. Ms. Yajnik reported that the BNP level was at least 150 pg/mL in 42 of the 124 measurements (39%). In 29 patients who had symptomatic heart failure and a pulmonary capillary wedge pressure of at least 15 mm Hg, the BNP level was at least 150 pg/mL in only 19 of the 42 measurements (45%).

“Therefore,” the researchers wrote in their abstract, “a BNP level of 150 pg/mL or greater was found to have a sensitivity of only 45.2%, a specificity of 64.9%, a positive predictive value of 3.7%, and a negative predictive value of 2.4% for the detection of heart failure in heart transplant recipients. In addition, a BNP value of 150 pg/mL or greater within 8 weeks of a clinically significant episode of rejection was noted in only 5 of 10 cases.”

Ms. Yajnik noted that the discrepancy between the use of B-type natriuretic peptide levels for detecting heart failure in the nontransplant and transplant populations requires further study. “Differences in the physiology between nontransplant patients and transplant patients may account for these disparate BNP levels,” she said.

CARMEL, CALIF. — B-type natriuretic peptide levels are not effective in detecting clinically relevant heart failure following heart transplantation, results from a study of 130 patients showed.

The finding is important because while the role of B-type natriuretic peptide (BNP) levels in detecting symptomatic heart failure in nontransplanted patients has been well established, its role in patients who have undergone heart transplantation is unclear.

“What we do know is that BNP is elevated right after [heart] transplant,” Meghana Yajnik said during a poster presentation at the Western regional meeting of the American Federation for Medical Research.

“However, several recent studies have said that BNP may have potential as a prognostic marker, in which high levels of BNP for prolonged periods after transplant may portend poorer outcome,” she noted

Ms. Yajnik, who is a second-year undergraduate student at University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 130 consecutive patients who received heart transplants at the university between July 2001 and November 2003. All of the patients had BNP levels assessed at the time of their right heart catheterization and their clinical exams.

The researchers defined heart failure as both the presence of symptoms (including dyspnea, edema, or a documented increase in diuretic dose), and a pulmonary capillary wedge pressure of 15 mm Hg or greater. BNP samples taken during the first 3 months post transplant and those taken in patients with renal insufficiency (defined as a creatinine level of greater than 1.9 mg/dL) were excluded from the analysis. The mean follow-up time was 28 months.

Of the 130 patients, 67 had 124 BNP measurements with a pulmonary capillary wedge pressure of at least 15 mm Hg. Ms. Yajnik reported that the BNP level was at least 150 pg/mL in 42 of the 124 measurements (39%). In 29 patients who had symptomatic heart failure and a pulmonary capillary wedge pressure of at least 15 mm Hg, the BNP level was at least 150 pg/mL in only 19 of the 42 measurements (45%).

“Therefore,” the researchers wrote in their abstract, “a BNP level of 150 pg/mL or greater was found to have a sensitivity of only 45.2%, a specificity of 64.9%, a positive predictive value of 3.7%, and a negative predictive value of 2.4% for the detection of heart failure in heart transplant recipients. In addition, a BNP value of 150 pg/mL or greater within 8 weeks of a clinically significant episode of rejection was noted in only 5 of 10 cases.”

Ms. Yajnik noted that the discrepancy between the use of B-type natriuretic peptide levels for detecting heart failure in the nontransplant and transplant populations requires further study. “Differences in the physiology between nontransplant patients and transplant patients may account for these disparate BNP levels,” she said.

CARMEL, CALIF. — The 5-year survival rate for heart retransplant patients who have severe heart failure symptoms with preserved systolic function is about 67%, results from a single-center study showed.

“These patients have comparable survival to patients retransplanted due to systolic dysfunction and therefore should be considered candidates for retransplantation,” Lakshmi Gokanapudy said at the Western regional meeting of the American Federation for Medical Research.

Ms. Gokanapudy, an undergraduate student at the University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 31 heart transplant patients who underwent retransplantation at the university during 1994–2004. The patients mean age at time of retransplantation was 51 years, and most (75%) were male.

Of the 31 patients, 24 (77%) had severe heart failure symptoms with preserved systolic function, which was defined as having a left ventricular ejection fraction of at least 40%.

Ms. Gokanapudy reported that each of the 24 patients with preserved systolic function had shortness of breath, fatigue, and decreased exercise tolerance. Echocardiography revealed that eight (33%) had left ventricular hypertrophy.

Five of the patients (21%) had no rejection episodes, 19 (79%) had an average of 1.4 rejection episodes, and 20 (83%) developed epicardial cardiac allograft vasculopathy.

The 5-year survival rate among the 24 patients with preserved systolic function was 67%, which was similar to the 5-year survival rate among the 7 retransplanted patients in the study who had severe systolic dysfunction (57%).

CARMEL, CALIF. — The 5-year survival rate for heart retransplant patients who have severe heart failure symptoms with preserved systolic function is about 67%, results from a single-center study showed.

“These patients have comparable survival to patients retransplanted due to systolic dysfunction and therefore should be considered candidates for retransplantation,” Lakshmi Gokanapudy said at the Western regional meeting of the American Federation for Medical Research.

Ms. Gokanapudy, an undergraduate student at the University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 31 heart transplant patients who underwent retransplantation at the university during 1994–2004. The patients mean age at time of retransplantation was 51 years, and most (75%) were male.

Of the 31 patients, 24 (77%) had severe heart failure symptoms with preserved systolic function, which was defined as having a left ventricular ejection fraction of at least 40%.

Ms. Gokanapudy reported that each of the 24 patients with preserved systolic function had shortness of breath, fatigue, and decreased exercise tolerance. Echocardiography revealed that eight (33%) had left ventricular hypertrophy.

Five of the patients (21%) had no rejection episodes, 19 (79%) had an average of 1.4 rejection episodes, and 20 (83%) developed epicardial cardiac allograft vasculopathy.

The 5-year survival rate among the 24 patients with preserved systolic function was 67%, which was similar to the 5-year survival rate among the 7 retransplanted patients in the study who had severe systolic dysfunction (57%).

CARMEL, CALIF. — The 5-year survival rate for heart retransplant patients who have severe heart failure symptoms with preserved systolic function is about 67%, results from a single-center study showed.

“These patients have comparable survival to patients retransplanted due to systolic dysfunction and therefore should be considered candidates for retransplantation,” Lakshmi Gokanapudy said at the Western regional meeting of the American Federation for Medical Research.

Ms. Gokanapudy, an undergraduate student at the University of California, Los Angeles, and her associates in the department of medicine at the university, evaluated 31 heart transplant patients who underwent retransplantation at the university during 1994–2004. The patients mean age at time of retransplantation was 51 years, and most (75%) were male.

Of the 31 patients, 24 (77%) had severe heart failure symptoms with preserved systolic function, which was defined as having a left ventricular ejection fraction of at least 40%.

Ms. Gokanapudy reported that each of the 24 patients with preserved systolic function had shortness of breath, fatigue, and decreased exercise tolerance. Echocardiography revealed that eight (33%) had left ventricular hypertrophy.

Five of the patients (21%) had no rejection episodes, 19 (79%) had an average of 1.4 rejection episodes, and 20 (83%) developed epicardial cardiac allograft vasculopathy.

The 5-year survival rate among the 24 patients with preserved systolic function was 67%, which was similar to the 5-year survival rate among the 7 retransplanted patients in the study who had severe systolic dysfunction (57%).

BETHESDA, MD. — More than half of patients in the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) are on two or more medications to treat their disease, said Dr. Michael McGoon, who is chairman of the registry's steering committee.

“One of the revealing outcomes early on … is that already 54% of the 460 patients on any pulmonary arterial hypertension medication are on two or more medications,” said Dr. McGoon, at a meeting on pulmonary hypertension sponsored by the National Institutes of Health.

The REVEAL registry is designed to look at the clinical course and medical management of pulmonary arterial hypertension. Researchers hope to enroll 3,000 patients with PAH, who will be followed for at least 5 years, regardless of their therapy. The registry is intended to capture demographic data and clinical treatment patterns and factors associated with improved clinical outcomes.

As of October 2006, 545 patients had been enrolled. Of these, slightly less than half (46%) had idiopathic PAH. Roughly half (51%) had PAH associated with other diseases. Of those enrolled, 71% also had cardiovascular disease, said Dr. McGoon, who is also director of the pulmonary hypertension clinic at the Mayo Medical School, Rochester, Minn.

The registry is sponsored by CoTherix Inc., which makes Ventavis (iloprost) for the treatment of pulmonary arterial hypertension. Dr. McGoon disclosed that he has financial ties to several pharmaceutical companies, including CoTherix.

BETHESDA, MD. — More than half of patients in the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) are on two or more medications to treat their disease, said Dr. Michael McGoon, who is chairman of the registry's steering committee.

“One of the revealing outcomes early on … is that already 54% of the 460 patients on any pulmonary arterial hypertension medication are on two or more medications,” said Dr. McGoon, at a meeting on pulmonary hypertension sponsored by the National Institutes of Health.

The REVEAL registry is designed to look at the clinical course and medical management of pulmonary arterial hypertension. Researchers hope to enroll 3,000 patients with PAH, who will be followed for at least 5 years, regardless of their therapy. The registry is intended to capture demographic data and clinical treatment patterns and factors associated with improved clinical outcomes.

As of October 2006, 545 patients had been enrolled. Of these, slightly less than half (46%) had idiopathic PAH. Roughly half (51%) had PAH associated with other diseases. Of those enrolled, 71% also had cardiovascular disease, said Dr. McGoon, who is also director of the pulmonary hypertension clinic at the Mayo Medical School, Rochester, Minn.

The registry is sponsored by CoTherix Inc., which makes Ventavis (iloprost) for the treatment of pulmonary arterial hypertension. Dr. McGoon disclosed that he has financial ties to several pharmaceutical companies, including CoTherix.

BETHESDA, MD. — More than half of patients in the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) are on two or more medications to treat their disease, said Dr. Michael McGoon, who is chairman of the registry's steering committee.

“One of the revealing outcomes early on … is that already 54% of the 460 patients on any pulmonary arterial hypertension medication are on two or more medications,” said Dr. McGoon, at a meeting on pulmonary hypertension sponsored by the National Institutes of Health.

The REVEAL registry is designed to look at the clinical course and medical management of pulmonary arterial hypertension. Researchers hope to enroll 3,000 patients with PAH, who will be followed for at least 5 years, regardless of their therapy. The registry is intended to capture demographic data and clinical treatment patterns and factors associated with improved clinical outcomes.

As of October 2006, 545 patients had been enrolled. Of these, slightly less than half (46%) had idiopathic PAH. Roughly half (51%) had PAH associated with other diseases. Of those enrolled, 71% also had cardiovascular disease, said Dr. McGoon, who is also director of the pulmonary hypertension clinic at the Mayo Medical School, Rochester, Minn.

The registry is sponsored by CoTherix Inc., which makes Ventavis (iloprost) for the treatment of pulmonary arterial hypertension. Dr. McGoon disclosed that he has financial ties to several pharmaceutical companies, including CoTherix.

SAN FRANCISCO — A majority of patients presenting to emergency departments with pulmonary edema have diastolic heart failure, also known as heart failure with preserved ejection fraction, Dr. William Grossman said.

A recent analysis of data from more than 100,000 hospitalizations in the Acute Decompensated Heart Failure Registry (ADHERE) showed that 51% of patients with heart failure had preserved ejection fractions, and 49% had depressed ejection fractions, also called systolic heart failure (J. Am. Coll. Cardiol. 2006;47:76–84). In-hospital mortality rates were 3% with diastolic heart failure and 4% with systolic heart failure, he said at a meeting sponsored by the California chapter of the American College of Cardiology.

That finding may surprise many people who attribute death from heart failure mainly to systolic dysfunction, said Dr. Grossman, chief of cardiology at the University of California, San Francisco. Many patients have both types of heart failure.

Compared with the systolic heart failure group, patients who had diastolic heart failure were more likely to be women and less likely to have a prior MI or to be taking ACE inhibitors or angiotensin receptor blockers (ARBs).

In a separate recent study, investigators from the Mayo Clinic, Rochester, Minn., followed 556 patients with heart failure in the community for 6 months. The mortality rate was 16% both in the 55% of patients with diastolic heart failure and in the rest of the cohort, who had systolic heart failure, Dr. Grossman noted.

“The prognosis is really not much better than for classic systolic heart failure,” he said at the meeting, also sponsored by the university.

In the Mayo Clinic study, diastolic dysfunction and the patient's ejection fraction independently predicted elevation of brain natriuretic peptide (BNP).

“When patients come to the emergency ward with acute shortness of breath, many of us look to the BNP to tell us, is this pneumonia? Is this asthma? Is this hypertension? BNP is elevated in heart failure whether it's systolic or diastolic,” an important fact to recognize, he said.

If diastolic heart failure is so widespread, what's causing it? It's not all caused by amyloidosis, and is unlikely to be due to untreated hypertension in so many cases, Dr. Grossman believes.

German investigators performed cardiac biopsies and other tests on 70 patients hospitalized with diastolic heart failure and found that 84% were infected with parvovirus B19. Presence of the virus was strongly associated with coronary endothelial dysfunction (Circulation 2005;111:879–86).

“I'm not saying this is what's going on in our emergency wards, but it's certainly something that I would never have thought to look for. We should pay attention. There may be increased information about this in the future,” Dr. Grossman commented.

There are few data from randomized trials to guide treatment of diastolic heart failure. Dr. Grossman approaches management much as he would for patients with systolic heart failure.

SAN FRANCISCO — A majority of patients presenting to emergency departments with pulmonary edema have diastolic heart failure, also known as heart failure with preserved ejection fraction, Dr. William Grossman said.

A recent analysis of data from more than 100,000 hospitalizations in the Acute Decompensated Heart Failure Registry (ADHERE) showed that 51% of patients with heart failure had preserved ejection fractions, and 49% had depressed ejection fractions, also called systolic heart failure (J. Am. Coll. Cardiol. 2006;47:76–84). In-hospital mortality rates were 3% with diastolic heart failure and 4% with systolic heart failure, he said at a meeting sponsored by the California chapter of the American College of Cardiology.

That finding may surprise many people who attribute death from heart failure mainly to systolic dysfunction, said Dr. Grossman, chief of cardiology at the University of California, San Francisco. Many patients have both types of heart failure.

Compared with the systolic heart failure group, patients who had diastolic heart failure were more likely to be women and less likely to have a prior MI or to be taking ACE inhibitors or angiotensin receptor blockers (ARBs).

In a separate recent study, investigators from the Mayo Clinic, Rochester, Minn., followed 556 patients with heart failure in the community for 6 months. The mortality rate was 16% both in the 55% of patients with diastolic heart failure and in the rest of the cohort, who had systolic heart failure, Dr. Grossman noted.

“The prognosis is really not much better than for classic systolic heart failure,” he said at the meeting, also sponsored by the university.

In the Mayo Clinic study, diastolic dysfunction and the patient's ejection fraction independently predicted elevation of brain natriuretic peptide (BNP).

“When patients come to the emergency ward with acute shortness of breath, many of us look to the BNP to tell us, is this pneumonia? Is this asthma? Is this hypertension? BNP is elevated in heart failure whether it's systolic or diastolic,” an important fact to recognize, he said.

If diastolic heart failure is so widespread, what's causing it? It's not all caused by amyloidosis, and is unlikely to be due to untreated hypertension in so many cases, Dr. Grossman believes.

German investigators performed cardiac biopsies and other tests on 70 patients hospitalized with diastolic heart failure and found that 84% were infected with parvovirus B19. Presence of the virus was strongly associated with coronary endothelial dysfunction (Circulation 2005;111:879–86).

“I'm not saying this is what's going on in our emergency wards, but it's certainly something that I would never have thought to look for. We should pay attention. There may be increased information about this in the future,” Dr. Grossman commented.

There are few data from randomized trials to guide treatment of diastolic heart failure. Dr. Grossman approaches management much as he would for patients with systolic heart failure.

SAN FRANCISCO — A majority of patients presenting to emergency departments with pulmonary edema have diastolic heart failure, also known as heart failure with preserved ejection fraction, Dr. William Grossman said.

A recent analysis of data from more than 100,000 hospitalizations in the Acute Decompensated Heart Failure Registry (ADHERE) showed that 51% of patients with heart failure had preserved ejection fractions, and 49% had depressed ejection fractions, also called systolic heart failure (J. Am. Coll. Cardiol. 2006;47:76–84). In-hospital mortality rates were 3% with diastolic heart failure and 4% with systolic heart failure, he said at a meeting sponsored by the California chapter of the American College of Cardiology.

That finding may surprise many people who attribute death from heart failure mainly to systolic dysfunction, said Dr. Grossman, chief of cardiology at the University of California, San Francisco. Many patients have both types of heart failure.

Compared with the systolic heart failure group, patients who had diastolic heart failure were more likely to be women and less likely to have a prior MI or to be taking ACE inhibitors or angiotensin receptor blockers (ARBs).

In a separate recent study, investigators from the Mayo Clinic, Rochester, Minn., followed 556 patients with heart failure in the community for 6 months. The mortality rate was 16% both in the 55% of patients with diastolic heart failure and in the rest of the cohort, who had systolic heart failure, Dr. Grossman noted.

“The prognosis is really not much better than for classic systolic heart failure,” he said at the meeting, also sponsored by the university.

In the Mayo Clinic study, diastolic dysfunction and the patient's ejection fraction independently predicted elevation of brain natriuretic peptide (BNP).

“When patients come to the emergency ward with acute shortness of breath, many of us look to the BNP to tell us, is this pneumonia? Is this asthma? Is this hypertension? BNP is elevated in heart failure whether it's systolic or diastolic,” an important fact to recognize, he said.

If diastolic heart failure is so widespread, what's causing it? It's not all caused by amyloidosis, and is unlikely to be due to untreated hypertension in so many cases, Dr. Grossman believes.

German investigators performed cardiac biopsies and other tests on 70 patients hospitalized with diastolic heart failure and found that 84% were infected with parvovirus B19. Presence of the virus was strongly associated with coronary endothelial dysfunction (Circulation 2005;111:879–86).

“I'm not saying this is what's going on in our emergency wards, but it's certainly something that I would never have thought to look for. We should pay attention. There may be increased information about this in the future,” Dr. Grossman commented.

There are few data from randomized trials to guide treatment of diastolic heart failure. Dr. Grossman approaches management much as he would for patients with systolic heart failure.

SALT LAKE CITY — The investigational endothelin receptor antagonist ambrisentan appears to provide a more favorable risk/benefit ratio than current therapies do for pulmonary artery hypertension, Dr. Lewis J. Rubin said at the annual meeting of the American College of Chest Physicians.

Results of the phase III randomized double-blind ARIES-I trial demonstrate that ambrisentan has good efficacy as once-daily oral therapy. What sets it apart from other effective endothelin receptor antagonists is that it displayed no liver toxicity in ARIES-I. Indeed, the incidence of liver function test abnormalities in the trial was zero, noted Dr. Rubin, professor of medicine at the University of California, San Diego.

Ambrisentan is a high-affinity propanoic acid-class endothelin receptor type A-selective agent with no interactions with warfarin or sildenafil. Its dosing is 10–100 times less than with bosentan—the endothelin receptor antagonist now on the market—and sitaxsentan, now under FDA review. Bosentan and sitaxsentan are oral twice-daily sulfonamide-class agents, and both are associated with dose-dependent increases in liver function abnormalities that can force treatment discontinuation.

ARIES-I involved 202 patients with pulmonary artery hypertension (PAH) who were randomized to 12 weeks of double-blind placebo or once-daily ambrisentan at 5 or 10 mg. Roughly two-thirds had idiopathic PAH. Most others had PAH associated with connective tissue disease. Most subjects had moderate disease; 58% of patients were WHO class III, while 32% of patients were class II. The mean baseline 6-minute walk distance was 341 m, indicative of moderate impairment.

The primary study end point was change in 6-minute walk distance over 12 weeks. It increased by 43.6 m with 10 mg/day of ambrisentan and 22.8 m with 5 mg, and it decreased by 7.8 m on placebo, suggesting a possible dose-response effect.

ARIES-I broke new ground as the first trial in PAH to use change in plasma brain natriuretic peptide (BNP) as a secondary end point. BNP is a marker of right heart stress. It reflects severity of PAH and is predictive of long-term outcome. BNP dropped by a mean of 62.5 and 149.3 pg/mL in patients on 5 and 10 mg/day of ambrisentan, respectively, while climbing 11.8 pg/mL with placebo.

In terms of other secondary end points, the Borg dyspnea index showed significant improvement in ambrisentan-treated patients. They were also only half as likely to experience clinical worsening during the study period. The ambrisentan arms showed nonsignificant trends for improvement in WHO functional class and on the Short Form-36 physical function scale.

Ambrisentan's chief side effects were peripheral edema, occurring in more than one-quarter of patients, and nasal congestion, in 9%. The edema is an endothelin receptor antagonist-class effect. It is typically mild and readily managed with low-dose diuretics without need for dose adjustment of the anti-PAH drug, Dr. Rubin said.

With a mean extended follow-up of 1.4 years and a maximum of 2.8 years, the incidence of confirmed liver function test abnormalities in ambrisentan-treated ARIES-I participants was 0.5%. That's less than the 3% incidence noted in the placebo arm during the 12-week double-blind treatment period.

Several audience members who have used ambrisentan said it's their impression there is a dose-response effect, although that hasn't been proven. Dr. Rubin agreed.

“I don't think that 10 mg is clearly superior to 7.5 mg, but my sense is that 5–7.5 mg is better than 2.5 mg. My guess is there's a potential advantage to having a range of doses with this drug, so you can start on the low side with the ability to increase,” he said.

Dr. Rubin is a consultant to Myogen Inc., which sponsored ARIES-I and was recently acquired by Gilead Sciences Inc. Giliad filed a new drug application with FDA in December, according to a statement. GlaxoSmithKline will market ambrisentan outside the United States.

Unlike other effective endothelin receptor antagonists, ambrisentan displayed no liver toxicity. DR. RUBIN

SALT LAKE CITY — The investigational endothelin receptor antagonist ambrisentan appears to provide a more favorable risk/benefit ratio than current therapies do for pulmonary artery hypertension, Dr. Lewis J. Rubin said at the annual meeting of the American College of Chest Physicians.

Results of the phase III randomized double-blind ARIES-I trial demonstrate that ambrisentan has good efficacy as once-daily oral therapy. What sets it apart from other effective endothelin receptor antagonists is that it displayed no liver toxicity in ARIES-I. Indeed, the incidence of liver function test abnormalities in the trial was zero, noted Dr. Rubin, professor of medicine at the University of California, San Diego.

Ambrisentan is a high-affinity propanoic acid-class endothelin receptor type A-selective agent with no interactions with warfarin or sildenafil. Its dosing is 10–100 times less than with bosentan—the endothelin receptor antagonist now on the market—and sitaxsentan, now under FDA review. Bosentan and sitaxsentan are oral twice-daily sulfonamide-class agents, and both are associated with dose-dependent increases in liver function abnormalities that can force treatment discontinuation.

ARIES-I involved 202 patients with pulmonary artery hypertension (PAH) who were randomized to 12 weeks of double-blind placebo or once-daily ambrisentan at 5 or 10 mg. Roughly two-thirds had idiopathic PAH. Most others had PAH associated with connective tissue disease. Most subjects had moderate disease; 58% of patients were WHO class III, while 32% of patients were class II. The mean baseline 6-minute walk distance was 341 m, indicative of moderate impairment.

The primary study end point was change in 6-minute walk distance over 12 weeks. It increased by 43.6 m with 10 mg/day of ambrisentan and 22.8 m with 5 mg, and it decreased by 7.8 m on placebo, suggesting a possible dose-response effect.

ARIES-I broke new ground as the first trial in PAH to use change in plasma brain natriuretic peptide (BNP) as a secondary end point. BNP is a marker of right heart stress. It reflects severity of PAH and is predictive of long-term outcome. BNP dropped by a mean of 62.5 and 149.3 pg/mL in patients on 5 and 10 mg/day of ambrisentan, respectively, while climbing 11.8 pg/mL with placebo.

In terms of other secondary end points, the Borg dyspnea index showed significant improvement in ambrisentan-treated patients. They were also only half as likely to experience clinical worsening during the study period. The ambrisentan arms showed nonsignificant trends for improvement in WHO functional class and on the Short Form-36 physical function scale.

Ambrisentan's chief side effects were peripheral edema, occurring in more than one-quarter of patients, and nasal congestion, in 9%. The edema is an endothelin receptor antagonist-class effect. It is typically mild and readily managed with low-dose diuretics without need for dose adjustment of the anti-PAH drug, Dr. Rubin said.

With a mean extended follow-up of 1.4 years and a maximum of 2.8 years, the incidence of confirmed liver function test abnormalities in ambrisentan-treated ARIES-I participants was 0.5%. That's less than the 3% incidence noted in the placebo arm during the 12-week double-blind treatment period.

Several audience members who have used ambrisentan said it's their impression there is a dose-response effect, although that hasn't been proven. Dr. Rubin agreed.

“I don't think that 10 mg is clearly superior to 7.5 mg, but my sense is that 5–7.5 mg is better than 2.5 mg. My guess is there's a potential advantage to having a range of doses with this drug, so you can start on the low side with the ability to increase,” he said.

Dr. Rubin is a consultant to Myogen Inc., which sponsored ARIES-I and was recently acquired by Gilead Sciences Inc. Giliad filed a new drug application with FDA in December, according to a statement. GlaxoSmithKline will market ambrisentan outside the United States.

Unlike other effective endothelin receptor antagonists, ambrisentan displayed no liver toxicity. DR. RUBIN

SALT LAKE CITY — The investigational endothelin receptor antagonist ambrisentan appears to provide a more favorable risk/benefit ratio than current therapies do for pulmonary artery hypertension, Dr. Lewis J. Rubin said at the annual meeting of the American College of Chest Physicians.

Results of the phase III randomized double-blind ARIES-I trial demonstrate that ambrisentan has good efficacy as once-daily oral therapy. What sets it apart from other effective endothelin receptor antagonists is that it displayed no liver toxicity in ARIES-I. Indeed, the incidence of liver function test abnormalities in the trial was zero, noted Dr. Rubin, professor of medicine at the University of California, San Diego.

Ambrisentan is a high-affinity propanoic acid-class endothelin receptor type A-selective agent with no interactions with warfarin or sildenafil. Its dosing is 10–100 times less than with bosentan—the endothelin receptor antagonist now on the market—and sitaxsentan, now under FDA review. Bosentan and sitaxsentan are oral twice-daily sulfonamide-class agents, and both are associated with dose-dependent increases in liver function abnormalities that can force treatment discontinuation.

ARIES-I involved 202 patients with pulmonary artery hypertension (PAH) who were randomized to 12 weeks of double-blind placebo or once-daily ambrisentan at 5 or 10 mg. Roughly two-thirds had idiopathic PAH. Most others had PAH associated with connective tissue disease. Most subjects had moderate disease; 58% of patients were WHO class III, while 32% of patients were class II. The mean baseline 6-minute walk distance was 341 m, indicative of moderate impairment.

The primary study end point was change in 6-minute walk distance over 12 weeks. It increased by 43.6 m with 10 mg/day of ambrisentan and 22.8 m with 5 mg, and it decreased by 7.8 m on placebo, suggesting a possible dose-response effect.

ARIES-I broke new ground as the first trial in PAH to use change in plasma brain natriuretic peptide (BNP) as a secondary end point. BNP is a marker of right heart stress. It reflects severity of PAH and is predictive of long-term outcome. BNP dropped by a mean of 62.5 and 149.3 pg/mL in patients on 5 and 10 mg/day of ambrisentan, respectively, while climbing 11.8 pg/mL with placebo.

In terms of other secondary end points, the Borg dyspnea index showed significant improvement in ambrisentan-treated patients. They were also only half as likely to experience clinical worsening during the study period. The ambrisentan arms showed nonsignificant trends for improvement in WHO functional class and on the Short Form-36 physical function scale.

Ambrisentan's chief side effects were peripheral edema, occurring in more than one-quarter of patients, and nasal congestion, in 9%. The edema is an endothelin receptor antagonist-class effect. It is typically mild and readily managed with low-dose diuretics without need for dose adjustment of the anti-PAH drug, Dr. Rubin said.

With a mean extended follow-up of 1.4 years and a maximum of 2.8 years, the incidence of confirmed liver function test abnormalities in ambrisentan-treated ARIES-I participants was 0.5%. That's less than the 3% incidence noted in the placebo arm during the 12-week double-blind treatment period.

Several audience members who have used ambrisentan said it's their impression there is a dose-response effect, although that hasn't been proven. Dr. Rubin agreed.

“I don't think that 10 mg is clearly superior to 7.5 mg, but my sense is that 5–7.5 mg is better than 2.5 mg. My guess is there's a potential advantage to having a range of doses with this drug, so you can start on the low side with the ability to increase,” he said.

Dr. Rubin is a consultant to Myogen Inc., which sponsored ARIES-I and was recently acquired by Gilead Sciences Inc. Giliad filed a new drug application with FDA in December, according to a statement. GlaxoSmithKline will market ambrisentan outside the United States.

Unlike other effective endothelin receptor antagonists, ambrisentan displayed no liver toxicity. DR. RUBIN

Severe heart failure can be reversed in some cases by using a left ventricular assist device to temporarily “unload” the myocardium plus a drug regimen to promote reverse remodeling, reported Dr. Emma J. Birks of the Royal Brompton and Harefield (England) National Health Service Trust and her associates.

In a study of 15 patients who received this treatment for nonischemic cardiomyopathy, 11 recovered sufficiently after a mean of 320 days to qualify for removal of the device. Ten of them survived with marked improvement that has persisted for over 4 years, the researchers said.

Following LVAD implantation, the patients received an ACE inhibitor (lisinopril), angiotensin-receptor blocker (losartan), a nonselective β-blocker (carvedilol), and an aldosterone antagonist (spironolactone) to enhance reverse remodeling. After maximal regression in the left ventricular end-diastolic diameter was achieved, the nonselective β-blocker was replaced with a selective β₁-blocker together with clenbuterol, a selective β₂-agonist, to prevent myocardial atrophy.

Eleven patients showed significant clinical improvement accompanied by marked functional changes in the myocardium and improved hemodynamics, exercise capacity, and quality of life. Ten (75%) fully recovered after the device was removed (N. Engl. J. Med. 2006;355:1873–84).

This study was supported in part by Thoratec, manufacturer of the HeartMate LVAD.

Severe heart failure can be reversed in some cases by using a left ventricular assist device to temporarily “unload” the myocardium plus a drug regimen to promote reverse remodeling, reported Dr. Emma J. Birks of the Royal Brompton and Harefield (England) National Health Service Trust and her associates.

In a study of 15 patients who received this treatment for nonischemic cardiomyopathy, 11 recovered sufficiently after a mean of 320 days to qualify for removal of the device. Ten of them survived with marked improvement that has persisted for over 4 years, the researchers said.

Following LVAD implantation, the patients received an ACE inhibitor (lisinopril), angiotensin-receptor blocker (losartan), a nonselective β-blocker (carvedilol), and an aldosterone antagonist (spironolactone) to enhance reverse remodeling. After maximal regression in the left ventricular end-diastolic diameter was achieved, the nonselective β-blocker was replaced with a selective β₁-blocker together with clenbuterol, a selective β₂-agonist, to prevent myocardial atrophy.

Eleven patients showed significant clinical improvement accompanied by marked functional changes in the myocardium and improved hemodynamics, exercise capacity, and quality of life. Ten (75%) fully recovered after the device was removed (N. Engl. J. Med. 2006;355:1873–84).

This study was supported in part by Thoratec, manufacturer of the HeartMate LVAD.

Severe heart failure can be reversed in some cases by using a left ventricular assist device to temporarily “unload” the myocardium plus a drug regimen to promote reverse remodeling, reported Dr. Emma J. Birks of the Royal Brompton and Harefield (England) National Health Service Trust and her associates.

In a study of 15 patients who received this treatment for nonischemic cardiomyopathy, 11 recovered sufficiently after a mean of 320 days to qualify for removal of the device. Ten of them survived with marked improvement that has persisted for over 4 years, the researchers said.

Following LVAD implantation, the patients received an ACE inhibitor (lisinopril), angiotensin-receptor blocker (losartan), a nonselective β-blocker (carvedilol), and an aldosterone antagonist (spironolactone) to enhance reverse remodeling. After maximal regression in the left ventricular end-diastolic diameter was achieved, the nonselective β-blocker was replaced with a selective β₁-blocker together with clenbuterol, a selective β₂-agonist, to prevent myocardial atrophy.

Eleven patients showed significant clinical improvement accompanied by marked functional changes in the myocardium and improved hemodynamics, exercise capacity, and quality of life. Ten (75%) fully recovered after the device was removed (N. Engl. J. Med. 2006;355:1873–84).

This study was supported in part by Thoratec, manufacturer of the HeartMate LVAD.

SEATTLE — Immune modulation therapy for patients with chronic heart failure did not reduce deaths or hospitalizations but was helpful in two subsets of patients in a 2,426-patient trial, Dr. Guillermo Torre-Amione reported.

Prespecified subgroup analyses found fewer deaths or hospitalizations with Celacade immune modulation therapy than with placebo in patients with New York Heart Association (NYHA) class II heart failure and in patients with class III-IV heart failure but no history of MI, he said at the annual meeting of the Heart Failure Society of America.

The randomized, double-blind, placebo-controlled Advanced Chronic Heart Failure Clinical Assessment of Immune Modulation Therapy (ACCLAIM) trial showed that the Celacade technology was safe and well tolerated and “helpful in heart failure from nonischemic etiology, and in patients with ischemic etiology who have not yet reached more advanced disease stages,” said Dr. Torre-Amione, medical director at the Methodist DeBakey Heart Center, Houston, and his associates.

Dr. Torre-Amione has received honoraria and research funding from Vasogen Inc., which funded the trial and owns the experimental Celacade technology.

Celacade therapy targets the chronic inflammation associated with cardiovascular disease. Samples of whole blood taken from patients randomized to Celacade therapy were subjected to oxidative stress and returned to patients via intramuscular injection. The oxidative stress induces cell apoptosis and triggers other reactions that increase production of anti-inflammatory cytokines and regulatory T cells that help reduce chronic inflammation, the investigators said.

Outpatient treatment with the 10-mL blood samples took place on days 1, 2, and 14, then every 30 days for 22 weeks or longer during June 2003-November 2005. All patients were on standard medications for heart failure, as tolerated. The mean follow-up in the study was 10 months.

There was no significant difference at 600 days between the Celacade and placebo groups in the primary combined end point of death from any cause or hospitalization for cardiovascular reasons. Quality-of-life scores were significantly better in the Celacade group than in placebo patients in preplanned analyses of secondary end points. The number of serious adverse events was similar between groups, as was the number of patients with more than one serious adverse event.

Among 900 patients with no prior MI, however, there were 26% fewer deaths or cardiovascular hospitalizations with Celacade compared with placebo, and patients fared better on secondary end points with Celacade as well, Dr. Torre-Amione said.

Among 700 patients with NYHA class II heart failure, there were 29% fewer deaths or cardiovascular hospitalizations with Celacade compared with placebo.

In a separate analysis of a combined group of 1,300 patients (about half of all patients in the study) with either class II heart failure or class III-IV but no history of MI, there were 165 deaths or heart failure hospitalizations in the Celacade group, compared with 226 in the placebo group, a highly statistically significant difference. In addition, the Celacade group had fewer mean days in the hospital for heart failure or for any cause, he said.

The study took place in 177 centers in North America, Europe, and Israel. Patients predominantly were white males and had a mean age of 64 years. All had a baseline ejection fraction of 30% or less and prior hospitalization (or outpatient treatment with IV medication) for heart failure within the previous 12 months. Sixty-two percent of patients had a history of MI.

SEATTLE — Immune modulation therapy for patients with chronic heart failure did not reduce deaths or hospitalizations but was helpful in two subsets of patients in a 2,426-patient trial, Dr. Guillermo Torre-Amione reported.

Prespecified subgroup analyses found fewer deaths or hospitalizations with Celacade immune modulation therapy than with placebo in patients with New York Heart Association (NYHA) class II heart failure and in patients with class III-IV heart failure but no history of MI, he said at the annual meeting of the Heart Failure Society of America.

The randomized, double-blind, placebo-controlled Advanced Chronic Heart Failure Clinical Assessment of Immune Modulation Therapy (ACCLAIM) trial showed that the Celacade technology was safe and well tolerated and “helpful in heart failure from nonischemic etiology, and in patients with ischemic etiology who have not yet reached more advanced disease stages,” said Dr. Torre-Amione, medical director at the Methodist DeBakey Heart Center, Houston, and his associates.

Dr. Torre-Amione has received honoraria and research funding from Vasogen Inc., which funded the trial and owns the experimental Celacade technology.

Celacade therapy targets the chronic inflammation associated with cardiovascular disease. Samples of whole blood taken from patients randomized to Celacade therapy were subjected to oxidative stress and returned to patients via intramuscular injection. The oxidative stress induces cell apoptosis and triggers other reactions that increase production of anti-inflammatory cytokines and regulatory T cells that help reduce chronic inflammation, the investigators said.

Outpatient treatment with the 10-mL blood samples took place on days 1, 2, and 14, then every 30 days for 22 weeks or longer during June 2003-November 2005. All patients were on standard medications for heart failure, as tolerated. The mean follow-up in the study was 10 months.

There was no significant difference at 600 days between the Celacade and placebo groups in the primary combined end point of death from any cause or hospitalization for cardiovascular reasons. Quality-of-life scores were significantly better in the Celacade group than in placebo patients in preplanned analyses of secondary end points. The number of serious adverse events was similar between groups, as was the number of patients with more than one serious adverse event.

Among 900 patients with no prior MI, however, there were 26% fewer deaths or cardiovascular hospitalizations with Celacade compared with placebo, and patients fared better on secondary end points with Celacade as well, Dr. Torre-Amione said.

Among 700 patients with NYHA class II heart failure, there were 29% fewer deaths or cardiovascular hospitalizations with Celacade compared with placebo.

In a separate analysis of a combined group of 1,300 patients (about half of all patients in the study) with either class II heart failure or class III-IV but no history of MI, there were 165 deaths or heart failure hospitalizations in the Celacade group, compared with 226 in the placebo group, a highly statistically significant difference. In addition, the Celacade group had fewer mean days in the hospital for heart failure or for any cause, he said.

The study took place in 177 centers in North America, Europe, and Israel. Patients predominantly were white males and had a mean age of 64 years. All had a baseline ejection fraction of 30% or less and prior hospitalization (or outpatient treatment with IV medication) for heart failure within the previous 12 months. Sixty-two percent of patients had a history of MI.

SEATTLE — Immune modulation therapy for patients with chronic heart failure did not reduce deaths or hospitalizations but was helpful in two subsets of patients in a 2,426-patient trial, Dr. Guillermo Torre-Amione reported.

Prespecified subgroup analyses found fewer deaths or hospitalizations with Celacade immune modulation therapy than with placebo in patients with New York Heart Association (NYHA) class II heart failure and in patients with class III-IV heart failure but no history of MI, he said at the annual meeting of the Heart Failure Society of America.

The randomized, double-blind, placebo-controlled Advanced Chronic Heart Failure Clinical Assessment of Immune Modulation Therapy (ACCLAIM) trial showed that the Celacade technology was safe and well tolerated and “helpful in heart failure from nonischemic etiology, and in patients with ischemic etiology who have not yet reached more advanced disease stages,” said Dr. Torre-Amione, medical director at the Methodist DeBakey Heart Center, Houston, and his associates.

Dr. Torre-Amione has received honoraria and research funding from Vasogen Inc., which funded the trial and owns the experimental Celacade technology.

Celacade therapy targets the chronic inflammation associated with cardiovascular disease. Samples of whole blood taken from patients randomized to Celacade therapy were subjected to oxidative stress and returned to patients via intramuscular injection. The oxidative stress induces cell apoptosis and triggers other reactions that increase production of anti-inflammatory cytokines and regulatory T cells that help reduce chronic inflammation, the investigators said.

Outpatient treatment with the 10-mL blood samples took place on days 1, 2, and 14, then every 30 days for 22 weeks or longer during June 2003-November 2005. All patients were on standard medications for heart failure, as tolerated. The mean follow-up in the study was 10 months.

There was no significant difference at 600 days between the Celacade and placebo groups in the primary combined end point of death from any cause or hospitalization for cardiovascular reasons. Quality-of-life scores were significantly better in the Celacade group than in placebo patients in preplanned analyses of secondary end points. The number of serious adverse events was similar between groups, as was the number of patients with more than one serious adverse event.

Among 900 patients with no prior MI, however, there were 26% fewer deaths or cardiovascular hospitalizations with Celacade compared with placebo, and patients fared better on secondary end points with Celacade as well, Dr. Torre-Amione said.

Among 700 patients with NYHA class II heart failure, there were 29% fewer deaths or cardiovascular hospitalizations with Celacade compared with placebo.

In a separate analysis of a combined group of 1,300 patients (about half of all patients in the study) with either class II heart failure or class III-IV but no history of MI, there were 165 deaths or heart failure hospitalizations in the Celacade group, compared with 226 in the placebo group, a highly statistically significant difference. In addition, the Celacade group had fewer mean days in the hospital for heart failure or for any cause, he said.

The study took place in 177 centers in North America, Europe, and Israel. Patients predominantly were white males and had a mean age of 64 years. All had a baseline ejection fraction of 30% or less and prior hospitalization (or outpatient treatment with IV medication) for heart failure within the previous 12 months. Sixty-two percent of patients had a history of MI.

CHICAGO — Most heart failure patients greatly overestimate the survival benefit provided by implantable cardioverter defibrillators, according to a new survey, Dr. Garrick C. Stewart reported at the annual scientific sessions of the American Heart Association.

The problem stems in part from the common practice of reporting clinical trial outcomes in terms of percent reduction in mortality. It creates confusion among patients, the public, and even physicians. This figure is actually a percent of a percent and is far greater than the number of deaths prevented or delayed, which is what really matters, added Dr. Stewart of Brigham and Women's Hospital, Boston.

“We advocate reporting event rates in persons per 100 to translate more clearly such information for our patients. We cannot stop reminding our patients and ourselves that heart failure remains a fatal disease from which most deaths occur slowly,” he stressed.

Dr. Stewart presented the results of a written survey completed by 104 patients with symptomatic heart failure who fit the profile of the study population in the landmark Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) which established the efficacy of ICDs for primary prevention of cardiac arrest. These were patients with a left ventricular ejection fraction below 35% and no history of cardiac arrest or syncope. Two-thirds already had an ICD.

More than half of those surveyed indicated they expected an ICD would save at least 50 lives per 100 recipients over a 5-year period. In reality, Dr. Stewart noted, SCD-HeFT showed the benefit is 7–8 lives saved.

“Frankly, the benefit is just not as big as we think,” observed coinvestigator Dr. Lynne Warner Stevenson, codirector of the cardiomyopathy and heart failure clinic at Brigham and Women's Hospital and professor of medicine at Harvard Medical School, Boston.

“We frequently have patients referred to us from other centers where they've been told that they must have an ICD put in place or they'll die. We think that's quite a disservice because it implies that the ICD will make them immortal,” she continued.

Two-thirds of survey participants who actually had an ICD thought the device would save their own lives. Fifty-five percent indicated they wouldn't deactivate it even if they were getting daily shocks, 70% would keep it on if they were dying of cancer, and 100% would keep the device on even if they were continuously struggling to breathe.

Dr. Stewart and Dr. Stevenson advocate a highly systematic approach to consenting patients for an ICD if they've never had a life-threatening arrhythmia.

“We actually have a script we use that says if we put an ICD in 100 patients with heart disease like yours, over the next 5 years we would expect that 30 patients would die anyway, 7 or 8 would be saved by the ICD, 10–20 would have a shock they don't need, 5–15 would have other complications, and the rest would not experience their device at all,” Dr. Stevenson said.

After hearing all of this, roughly one-third of patients still want a device, one-third decide they definitely don't, and one-third want to think it over some more.

Underscoring the point that ICDs partially protect against sudden arrhythmic death but don't prevent a slower death from pump failure, Dr. Jean-Yves F. Le Heuzey presented outcome data on 2,418 patients who got an ICD at 22 French hospitals during 2001–2003.

Mortality was 11.3% by 2005. Forty-two percent of deaths resulted from pump failure, 8.7% from cardiac arrest with electromechanical dissociation, and 6.2% were due to arrhythmic storm. Cancer and septic shock each accounted for 6.5% of deaths, said Dr. Le Heuzey, professor of cardiology at George Pompidou European Hospital, Paris.

More than half of those surveyed said they expected an ICD would save at least 50 lives per 100 recipients over 5 years. DR. STEWART

CHICAGO — Most heart failure patients greatly overestimate the survival benefit provided by implantable cardioverter defibrillators, according to a new survey, Dr. Garrick C. Stewart reported at the annual scientific sessions of the American Heart Association.

The problem stems in part from the common practice of reporting clinical trial outcomes in terms of percent reduction in mortality. It creates confusion among patients, the public, and even physicians. This figure is actually a percent of a percent and is far greater than the number of deaths prevented or delayed, which is what really matters, added Dr. Stewart of Brigham and Women's Hospital, Boston.

“We advocate reporting event rates in persons per 100 to translate more clearly such information for our patients. We cannot stop reminding our patients and ourselves that heart failure remains a fatal disease from which most deaths occur slowly,” he stressed.

Dr. Stewart presented the results of a written survey completed by 104 patients with symptomatic heart failure who fit the profile of the study population in the landmark Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) which established the efficacy of ICDs for primary prevention of cardiac arrest. These were patients with a left ventricular ejection fraction below 35% and no history of cardiac arrest or syncope. Two-thirds already had an ICD.

More than half of those surveyed indicated they expected an ICD would save at least 50 lives per 100 recipients over a 5-year period. In reality, Dr. Stewart noted, SCD-HeFT showed the benefit is 7–8 lives saved.

“Frankly, the benefit is just not as big as we think,” observed coinvestigator Dr. Lynne Warner Stevenson, codirector of the cardiomyopathy and heart failure clinic at Brigham and Women's Hospital and professor of medicine at Harvard Medical School, Boston.

“We frequently have patients referred to us from other centers where they've been told that they must have an ICD put in place or they'll die. We think that's quite a disservice because it implies that the ICD will make them immortal,” she continued.

Two-thirds of survey participants who actually had an ICD thought the device would save their own lives. Fifty-five percent indicated they wouldn't deactivate it even if they were getting daily shocks, 70% would keep it on if they were dying of cancer, and 100% would keep the device on even if they were continuously struggling to breathe.

Dr. Stewart and Dr. Stevenson advocate a highly systematic approach to consenting patients for an ICD if they've never had a life-threatening arrhythmia.

“We actually have a script we use that says if we put an ICD in 100 patients with heart disease like yours, over the next 5 years we would expect that 30 patients would die anyway, 7 or 8 would be saved by the ICD, 10–20 would have a shock they don't need, 5–15 would have other complications, and the rest would not experience their device at all,” Dr. Stevenson said.

After hearing all of this, roughly one-third of patients still want a device, one-third decide they definitely don't, and one-third want to think it over some more.

Underscoring the point that ICDs partially protect against sudden arrhythmic death but don't prevent a slower death from pump failure, Dr. Jean-Yves F. Le Heuzey presented outcome data on 2,418 patients who got an ICD at 22 French hospitals during 2001–2003.

Mortality was 11.3% by 2005. Forty-two percent of deaths resulted from pump failure, 8.7% from cardiac arrest with electromechanical dissociation, and 6.2% were due to arrhythmic storm. Cancer and septic shock each accounted for 6.5% of deaths, said Dr. Le Heuzey, professor of cardiology at George Pompidou European Hospital, Paris.

More than half of those surveyed said they expected an ICD would save at least 50 lives per 100 recipients over 5 years. DR. STEWART

CHICAGO — Most heart failure patients greatly overestimate the survival benefit provided by implantable cardioverter defibrillators, according to a new survey, Dr. Garrick C. Stewart reported at the annual scientific sessions of the American Heart Association.

The problem stems in part from the common practice of reporting clinical trial outcomes in terms of percent reduction in mortality. It creates confusion among patients, the public, and even physicians. This figure is actually a percent of a percent and is far greater than the number of deaths prevented or delayed, which is what really matters, added Dr. Stewart of Brigham and Women's Hospital, Boston.

“We advocate reporting event rates in persons per 100 to translate more clearly such information for our patients. We cannot stop reminding our patients and ourselves that heart failure remains a fatal disease from which most deaths occur slowly,” he stressed.

Dr. Stewart presented the results of a written survey completed by 104 patients with symptomatic heart failure who fit the profile of the study population in the landmark Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) which established the efficacy of ICDs for primary prevention of cardiac arrest. These were patients with a left ventricular ejection fraction below 35% and no history of cardiac arrest or syncope. Two-thirds already had an ICD.

More than half of those surveyed indicated they expected an ICD would save at least 50 lives per 100 recipients over a 5-year period. In reality, Dr. Stewart noted, SCD-HeFT showed the benefit is 7–8 lives saved.

“Frankly, the benefit is just not as big as we think,” observed coinvestigator Dr. Lynne Warner Stevenson, codirector of the cardiomyopathy and heart failure clinic at Brigham and Women's Hospital and professor of medicine at Harvard Medical School, Boston.

“We frequently have patients referred to us from other centers where they've been told that they must have an ICD put in place or they'll die. We think that's quite a disservice because it implies that the ICD will make them immortal,” she continued.

Two-thirds of survey participants who actually had an ICD thought the device would save their own lives. Fifty-five percent indicated they wouldn't deactivate it even if they were getting daily shocks, 70% would keep it on if they were dying of cancer, and 100% would keep the device on even if they were continuously struggling to breathe.

Dr. Stewart and Dr. Stevenson advocate a highly systematic approach to consenting patients for an ICD if they've never had a life-threatening arrhythmia.

“We actually have a script we use that says if we put an ICD in 100 patients with heart disease like yours, over the next 5 years we would expect that 30 patients would die anyway, 7 or 8 would be saved by the ICD, 10–20 would have a shock they don't need, 5–15 would have other complications, and the rest would not experience their device at all,” Dr. Stevenson said.

After hearing all of this, roughly one-third of patients still want a device, one-third decide they definitely don't, and one-third want to think it over some more.

Underscoring the point that ICDs partially protect against sudden arrhythmic death but don't prevent a slower death from pump failure, Dr. Jean-Yves F. Le Heuzey presented outcome data on 2,418 patients who got an ICD at 22 French hospitals during 2001–2003.

Mortality was 11.3% by 2005. Forty-two percent of deaths resulted from pump failure, 8.7% from cardiac arrest with electromechanical dissociation, and 6.2% were due to arrhythmic storm. Cancer and septic shock each accounted for 6.5% of deaths, said Dr. Le Heuzey, professor of cardiology at George Pompidou European Hospital, Paris.

More than half of those surveyed said they expected an ICD would save at least 50 lives per 100 recipients over 5 years. DR. STEWART