Heart Failure

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

VIENNA — The dopamine agonist bromocriptine shows considerable promise for the treatment of peripartum cardiomyopathy, Dr. Olaf Forster said at the annual congress of the European Society of Cardiology.

“The results obtained by the addition of bromocriptine to standard heart failure treatment in this study are encouraging. Bromocriptine may represent a novel therapeutic approach in the treatment of peripartum cardiomyopathy, but the data need to be considered as preliminary,” according to Dr. Forster of the University of the Witwatersrand, Johannesburg, South Africa.

The hallmark of peripartum cardiomyopathy (PPCM) is onset of left ventricular failure between 1 month before and 5 months after delivery. The highest rates of PPCM in the world are reported in South Africa. “We get two or three new patients per week in Soweto,” said Dr. Forster, who is with the university's cardiovascular research unit at the Chris Hani Baragwanath Hospital, Soweto.

Treatment of PPCM involves standard heart failure medications and firm advice to avoid further pregnancies. A subsequent pregnancy can be fatal; half of women who become pregnant again after a first episode of PPCM experience long-term worsening of heart failure, whereas the other half return to their normal prepregnancy left ventricular systolic function.

Dr. Forster reported on 16 indigenous black women ages 26–39 with PPCM who presented with a subsequent pregnancy 1–6 years following their index PPCM pregnancy. The first six women—the control group—didn't receive bromocriptine because their pregnancies occurred before the South African team learned of evidence from German studies in knockout mice suggesting that the drug might be beneficial in PPCM. The next 10 patients received bromocriptine at 2.5 mg b.i.d. for 2 months beginning 4 hours post delivery. This was the first study of the drug in human PPCM.

All 16 patients were on a diuretic and β-blocker during pregnancy, with an ACE inhibitor added post partum.

The mean left ventricular ejection fraction in controls was 44% at baseline, declining to 36% at 1 month post partum and to 25% 3 months post partum. In contrast, the baseline ejection fraction was 51% in the bromocriptine-treated group, dropping to 43% 1 month post partum, and rebounding to 55% by 3 months post partum.

At 3 months post partum, 2 of 6 controls were dead of heart failure, compared with none of the 10 women who received bromocriptine.

Bromocriptine had no side effects, but some women on the prolactin inhibitor were quite disturbed that they couldn't breast feed, according to Dr. Forster.

In the STAT3 female knockout mouse model of PPCM, enhanced postpartum oxidative stress results in cathepsin D-facilitated cleavage of the 23-kd form of prolactin into its 16-kd form, which is proapoptotic and antiangiogenic. This short-form prolactin disrupts endothelial cell function and promotes vasoconstriction, resulting in impaired cardiac microcirculation, increased cardiac apoptosis, and reduced postpartum survival. Bromocriptine prevents PPCM in this model.

Session cochair Dr. Robert Califf, vice-chancellor for clinical research, director of the Translational Medicine Institute, and professor of medicine at Duke University, Durham, N.C., called the clinical results encouraging, but wondered why the investigators hadn't mounted a randomized trial. Dr. Forster replied that the risks posed by subsequent pregnancy in women with PPCM are so great that he and his coworkers believe it would be unethical to deny them bromocriptine. “The risk is simply too high—and we can see that it works,” he explained.

However, a randomized trial is ongoing in women experiencing a first episode of PPCM, Dr. Forster added.

VIENNA — The dopamine agonist bromocriptine shows considerable promise for the treatment of peripartum cardiomyopathy, Dr. Olaf Forster said at the annual congress of the European Society of Cardiology.

“The results obtained by the addition of bromocriptine to standard heart failure treatment in this study are encouraging. Bromocriptine may represent a novel therapeutic approach in the treatment of peripartum cardiomyopathy, but the data need to be considered as preliminary,” according to Dr. Forster of the University of the Witwatersrand, Johannesburg, South Africa.

The hallmark of peripartum cardiomyopathy (PPCM) is onset of left ventricular failure between 1 month before and 5 months after delivery. The highest rates of PPCM in the world are reported in South Africa. “We get two or three new patients per week in Soweto,” said Dr. Forster, who is with the university's cardiovascular research unit at the Chris Hani Baragwanath Hospital, Soweto.

Treatment of PPCM involves standard heart failure medications and firm advice to avoid further pregnancies. A subsequent pregnancy can be fatal; half of women who become pregnant again after a first episode of PPCM experience long-term worsening of heart failure, whereas the other half return to their normal prepregnancy left ventricular systolic function.

Dr. Forster reported on 16 indigenous black women ages 26–39 with PPCM who presented with a subsequent pregnancy 1–6 years following their index PPCM pregnancy. The first six women—the control group—didn't receive bromocriptine because their pregnancies occurred before the South African team learned of evidence from German studies in knockout mice suggesting that the drug might be beneficial in PPCM. The next 10 patients received bromocriptine at 2.5 mg b.i.d. for 2 months beginning 4 hours post delivery. This was the first study of the drug in human PPCM.

All 16 patients were on a diuretic and β-blocker during pregnancy, with an ACE inhibitor added post partum.

The mean left ventricular ejection fraction in controls was 44% at baseline, declining to 36% at 1 month post partum and to 25% 3 months post partum. In contrast, the baseline ejection fraction was 51% in the bromocriptine-treated group, dropping to 43% 1 month post partum, and rebounding to 55% by 3 months post partum.

At 3 months post partum, 2 of 6 controls were dead of heart failure, compared with none of the 10 women who received bromocriptine.

Bromocriptine had no side effects, but some women on the prolactin inhibitor were quite disturbed that they couldn't breast feed, according to Dr. Forster.

In the STAT3 female knockout mouse model of PPCM, enhanced postpartum oxidative stress results in cathepsin D-facilitated cleavage of the 23-kd form of prolactin into its 16-kd form, which is proapoptotic and antiangiogenic. This short-form prolactin disrupts endothelial cell function and promotes vasoconstriction, resulting in impaired cardiac microcirculation, increased cardiac apoptosis, and reduced postpartum survival. Bromocriptine prevents PPCM in this model.

Session cochair Dr. Robert Califf, vice-chancellor for clinical research, director of the Translational Medicine Institute, and professor of medicine at Duke University, Durham, N.C., called the clinical results encouraging, but wondered why the investigators hadn't mounted a randomized trial. Dr. Forster replied that the risks posed by subsequent pregnancy in women with PPCM are so great that he and his coworkers believe it would be unethical to deny them bromocriptine. “The risk is simply too high—and we can see that it works,” he explained.

However, a randomized trial is ongoing in women experiencing a first episode of PPCM, Dr. Forster added.

VIENNA — The dopamine agonist bromocriptine shows considerable promise for the treatment of peripartum cardiomyopathy, Dr. Olaf Forster said at the annual congress of the European Society of Cardiology.

“The results obtained by the addition of bromocriptine to standard heart failure treatment in this study are encouraging. Bromocriptine may represent a novel therapeutic approach in the treatment of peripartum cardiomyopathy, but the data need to be considered as preliminary,” according to Dr. Forster of the University of the Witwatersrand, Johannesburg, South Africa.

The hallmark of peripartum cardiomyopathy (PPCM) is onset of left ventricular failure between 1 month before and 5 months after delivery. The highest rates of PPCM in the world are reported in South Africa. “We get two or three new patients per week in Soweto,” said Dr. Forster, who is with the university's cardiovascular research unit at the Chris Hani Baragwanath Hospital, Soweto.

Treatment of PPCM involves standard heart failure medications and firm advice to avoid further pregnancies. A subsequent pregnancy can be fatal; half of women who become pregnant again after a first episode of PPCM experience long-term worsening of heart failure, whereas the other half return to their normal prepregnancy left ventricular systolic function.

Dr. Forster reported on 16 indigenous black women ages 26–39 with PPCM who presented with a subsequent pregnancy 1–6 years following their index PPCM pregnancy. The first six women—the control group—didn't receive bromocriptine because their pregnancies occurred before the South African team learned of evidence from German studies in knockout mice suggesting that the drug might be beneficial in PPCM. The next 10 patients received bromocriptine at 2.5 mg b.i.d. for 2 months beginning 4 hours post delivery. This was the first study of the drug in human PPCM.

All 16 patients were on a diuretic and β-blocker during pregnancy, with an ACE inhibitor added post partum.

The mean left ventricular ejection fraction in controls was 44% at baseline, declining to 36% at 1 month post partum and to 25% 3 months post partum. In contrast, the baseline ejection fraction was 51% in the bromocriptine-treated group, dropping to 43% 1 month post partum, and rebounding to 55% by 3 months post partum.

At 3 months post partum, 2 of 6 controls were dead of heart failure, compared with none of the 10 women who received bromocriptine.

Bromocriptine had no side effects, but some women on the prolactin inhibitor were quite disturbed that they couldn't breast feed, according to Dr. Forster.

In the STAT3 female knockout mouse model of PPCM, enhanced postpartum oxidative stress results in cathepsin D-facilitated cleavage of the 23-kd form of prolactin into its 16-kd form, which is proapoptotic and antiangiogenic. This short-form prolactin disrupts endothelial cell function and promotes vasoconstriction, resulting in impaired cardiac microcirculation, increased cardiac apoptosis, and reduced postpartum survival. Bromocriptine prevents PPCM in this model.

Session cochair Dr. Robert Califf, vice-chancellor for clinical research, director of the Translational Medicine Institute, and professor of medicine at Duke University, Durham, N.C., called the clinical results encouraging, but wondered why the investigators hadn't mounted a randomized trial. Dr. Forster replied that the risks posed by subsequent pregnancy in women with PPCM are so great that he and his coworkers believe it would be unethical to deny them bromocriptine. “The risk is simply too high—and we can see that it works,” he explained.

However, a randomized trial is ongoing in women experiencing a first episode of PPCM, Dr. Forster added.

Updated clinical practice guidelines for the medical management of pulmonary arterial hypertension from the American College of Chest Physicians reflect findings from several recent clinical trials as well as the additional drugs that have been approved since the previous guidelines were issued in 2004.

The guidelines include an evidence-based, updated treatment algorithm intended to assist physicians in decision making (Chest 2007;131:1917–28).

Providing new data were two “important” studies that demonstrated survival benefits in patients treated with bosentan, which binds to both endothelin receptors (ETA and ETB), according to lead author Dr. David B. Badesch of the University of Colorado Health Sciences Center, Denver.

In the first study, 169 patients (aged 13–80 years) with class III or IV PAH were treated with bosentan as first-line therapy. Survival was 96% at 12 months and 89% at 24 months, in contrast to predicted survival rates from the earlier National Institutes of Health registry of 69% and 57%, respectively (Eur. Respir. J. 2005;25:244–9).

In the second study, survival in 139 patients treated with bosentan was compared with historical data from 346 patients who had been treated with epoprostenol. Survival estimates after 1 and 2 years were 97% and 91%, respectively, in the bosentan-treated group, and 91% and 84% in the epoprostenol-treated group (Thorax 2005;60:1025–30).

Baseline characteristics of the patients suggested that the epoprostenol patients had more severe disease. But Cox regression analyses adjusting for baseline factors showed a greater risk of death in the epoprostenol group (hazard ratio 2.2).

Bosentan also has now been evaluated in children with PAH associated with congenital heart disease or connective tissue disease. In a retrospective study, 86 children were treated with bosentan with or without concomitant epoprostenol or treprostinil. WHO functional class improved in 46% of patients and was unchanged in 44%, and survival estimates at 1 and 2 years were 98% and 91% (J. Am. Coll. Cardiol. 2005;46:697–704).

Another recent study included 245 patients (ranging in age from 12 years to 78 years) who received bosentan, placebo, or one of two doses of a selective ETA endothelin receptor antagonist, sitaxsentan. At week 18, patients receiving the higher dose of sitaxsentan (100 mg/day) had significant improvements on a 6-minute walk test, compared with those receiving placebo. The incidence of elevated transaminases was 6% in the placebo group, 5% in the sitaxsentan low-dose (50 mg/day) group, 3% in the high-dose sitaxsentan group, and 11% in the bosentan group (J. Am. Coll. Cardiol. 2006;47:2049–56).

Sitaxsentan remains investigational in the United States, but has been approved for use in Europe and Canada.

A second selective ETA endothelin receptor antagonist, ambrisentan, was evaluated in a double-blind, dose-ranging study that included 64 adult patients with PAH. They were randomized to receive 1 mg, 2.5 mg, 5 mg, or 10 mg of ambrisentan orally once daily for 12 weeks. The 6-minute walk test improved significantly for all groups, with a mean increase from baseline of 36.1 meters. Improvements also were seen in WHO functional class, Borg dyspnea index, and cardiac index (J. Am. Coll. Cardiol. 2005;46:529–35).

Adverse events were mild, with elevated serum aminotransferase exceeding three times the upper limit of normal seen in 3.1% of patients. This drug was recently approved for class II and class III PAH in the United States.

The phosphodiesterase inhibitor sildenafil also is now approved for the treatment of all classes of PAH in a dosage of 20 mg three times daily. The drug was evaluated in a double-blind study that randomized 278 patients (mean age 50 years) to placebo or 20, 40, or 80 mg three times daily for 12 weeks.

Improvements were seen in the 6-minute walk test in all groups, with placebo-corrected treatment effects being +13%, +13.3%, and +14.7% in the 20-, 40-, and 80-mg groups, respectively. The incidence of clinical worsening did not differ significantly between the placebo and sildenafil groups. Side effects included flushing, dyspepsia, and diarrhea.

In summarizing the treatment options, the authors noted that for patients in functional class II, the only current recommended drugs are sildenafil and subcutaneous and intravenous treprostinil, and suggested that sildenafil may be the first choice for most patients because of ease of administration and relative efficacy.

For patients in functional class III, five drugs are available: bosentan, sildenafil, intravenous epoprostenol, inhaled iloprost, and subcutaneous or intravenous treprostinil. For those with early class III disease, oral bosentan or sildenafil may be used, with the choice reflecting relative toxicities. For patients with more advanced disease, prostanoid therapy may be needed.

All the available agents are approved for patients with class IV PAH. However, the authors wrote, “[we] strongly encourage IV epoprostenol as the treatment of choice for these most critically ill patients. IV epoprostenol has a rapid and predictable onset of action, and most experts are familiar with how to titrate this drug in the acute setting.”

Updated clinical practice guidelines for the medical management of pulmonary arterial hypertension from the American College of Chest Physicians reflect findings from several recent clinical trials as well as the additional drugs that have been approved since the previous guidelines were issued in 2004.

The guidelines include an evidence-based, updated treatment algorithm intended to assist physicians in decision making (Chest 2007;131:1917–28).

Providing new data were two “important” studies that demonstrated survival benefits in patients treated with bosentan, which binds to both endothelin receptors (ETA and ETB), according to lead author Dr. David B. Badesch of the University of Colorado Health Sciences Center, Denver.

In the first study, 169 patients (aged 13–80 years) with class III or IV PAH were treated with bosentan as first-line therapy. Survival was 96% at 12 months and 89% at 24 months, in contrast to predicted survival rates from the earlier National Institutes of Health registry of 69% and 57%, respectively (Eur. Respir. J. 2005;25:244–9).

In the second study, survival in 139 patients treated with bosentan was compared with historical data from 346 patients who had been treated with epoprostenol. Survival estimates after 1 and 2 years were 97% and 91%, respectively, in the bosentan-treated group, and 91% and 84% in the epoprostenol-treated group (Thorax 2005;60:1025–30).

Baseline characteristics of the patients suggested that the epoprostenol patients had more severe disease. But Cox regression analyses adjusting for baseline factors showed a greater risk of death in the epoprostenol group (hazard ratio 2.2).

Bosentan also has now been evaluated in children with PAH associated with congenital heart disease or connective tissue disease. In a retrospective study, 86 children were treated with bosentan with or without concomitant epoprostenol or treprostinil. WHO functional class improved in 46% of patients and was unchanged in 44%, and survival estimates at 1 and 2 years were 98% and 91% (J. Am. Coll. Cardiol. 2005;46:697–704).

Another recent study included 245 patients (ranging in age from 12 years to 78 years) who received bosentan, placebo, or one of two doses of a selective ETA endothelin receptor antagonist, sitaxsentan. At week 18, patients receiving the higher dose of sitaxsentan (100 mg/day) had significant improvements on a 6-minute walk test, compared with those receiving placebo. The incidence of elevated transaminases was 6% in the placebo group, 5% in the sitaxsentan low-dose (50 mg/day) group, 3% in the high-dose sitaxsentan group, and 11% in the bosentan group (J. Am. Coll. Cardiol. 2006;47:2049–56).

Sitaxsentan remains investigational in the United States, but has been approved for use in Europe and Canada.

A second selective ETA endothelin receptor antagonist, ambrisentan, was evaluated in a double-blind, dose-ranging study that included 64 adult patients with PAH. They were randomized to receive 1 mg, 2.5 mg, 5 mg, or 10 mg of ambrisentan orally once daily for 12 weeks. The 6-minute walk test improved significantly for all groups, with a mean increase from baseline of 36.1 meters. Improvements also were seen in WHO functional class, Borg dyspnea index, and cardiac index (J. Am. Coll. Cardiol. 2005;46:529–35).

Adverse events were mild, with elevated serum aminotransferase exceeding three times the upper limit of normal seen in 3.1% of patients. This drug was recently approved for class II and class III PAH in the United States.

The phosphodiesterase inhibitor sildenafil also is now approved for the treatment of all classes of PAH in a dosage of 20 mg three times daily. The drug was evaluated in a double-blind study that randomized 278 patients (mean age 50 years) to placebo or 20, 40, or 80 mg three times daily for 12 weeks.

Improvements were seen in the 6-minute walk test in all groups, with placebo-corrected treatment effects being +13%, +13.3%, and +14.7% in the 20-, 40-, and 80-mg groups, respectively. The incidence of clinical worsening did not differ significantly between the placebo and sildenafil groups. Side effects included flushing, dyspepsia, and diarrhea.

In summarizing the treatment options, the authors noted that for patients in functional class II, the only current recommended drugs are sildenafil and subcutaneous and intravenous treprostinil, and suggested that sildenafil may be the first choice for most patients because of ease of administration and relative efficacy.

For patients in functional class III, five drugs are available: bosentan, sildenafil, intravenous epoprostenol, inhaled iloprost, and subcutaneous or intravenous treprostinil. For those with early class III disease, oral bosentan or sildenafil may be used, with the choice reflecting relative toxicities. For patients with more advanced disease, prostanoid therapy may be needed.

All the available agents are approved for patients with class IV PAH. However, the authors wrote, “[we] strongly encourage IV epoprostenol as the treatment of choice for these most critically ill patients. IV epoprostenol has a rapid and predictable onset of action, and most experts are familiar with how to titrate this drug in the acute setting.”

Updated clinical practice guidelines for the medical management of pulmonary arterial hypertension from the American College of Chest Physicians reflect findings from several recent clinical trials as well as the additional drugs that have been approved since the previous guidelines were issued in 2004.

The guidelines include an evidence-based, updated treatment algorithm intended to assist physicians in decision making (Chest 2007;131:1917–28).

Providing new data were two “important” studies that demonstrated survival benefits in patients treated with bosentan, which binds to both endothelin receptors (ETA and ETB), according to lead author Dr. David B. Badesch of the University of Colorado Health Sciences Center, Denver.

In the first study, 169 patients (aged 13–80 years) with class III or IV PAH were treated with bosentan as first-line therapy. Survival was 96% at 12 months and 89% at 24 months, in contrast to predicted survival rates from the earlier National Institutes of Health registry of 69% and 57%, respectively (Eur. Respir. J. 2005;25:244–9).

In the second study, survival in 139 patients treated with bosentan was compared with historical data from 346 patients who had been treated with epoprostenol. Survival estimates after 1 and 2 years were 97% and 91%, respectively, in the bosentan-treated group, and 91% and 84% in the epoprostenol-treated group (Thorax 2005;60:1025–30).

Baseline characteristics of the patients suggested that the epoprostenol patients had more severe disease. But Cox regression analyses adjusting for baseline factors showed a greater risk of death in the epoprostenol group (hazard ratio 2.2).

Bosentan also has now been evaluated in children with PAH associated with congenital heart disease or connective tissue disease. In a retrospective study, 86 children were treated with bosentan with or without concomitant epoprostenol or treprostinil. WHO functional class improved in 46% of patients and was unchanged in 44%, and survival estimates at 1 and 2 years were 98% and 91% (J. Am. Coll. Cardiol. 2005;46:697–704).

Another recent study included 245 patients (ranging in age from 12 years to 78 years) who received bosentan, placebo, or one of two doses of a selective ETA endothelin receptor antagonist, sitaxsentan. At week 18, patients receiving the higher dose of sitaxsentan (100 mg/day) had significant improvements on a 6-minute walk test, compared with those receiving placebo. The incidence of elevated transaminases was 6% in the placebo group, 5% in the sitaxsentan low-dose (50 mg/day) group, 3% in the high-dose sitaxsentan group, and 11% in the bosentan group (J. Am. Coll. Cardiol. 2006;47:2049–56).

Sitaxsentan remains investigational in the United States, but has been approved for use in Europe and Canada.

A second selective ETA endothelin receptor antagonist, ambrisentan, was evaluated in a double-blind, dose-ranging study that included 64 adult patients with PAH. They were randomized to receive 1 mg, 2.5 mg, 5 mg, or 10 mg of ambrisentan orally once daily for 12 weeks. The 6-minute walk test improved significantly for all groups, with a mean increase from baseline of 36.1 meters. Improvements also were seen in WHO functional class, Borg dyspnea index, and cardiac index (J. Am. Coll. Cardiol. 2005;46:529–35).

Adverse events were mild, with elevated serum aminotransferase exceeding three times the upper limit of normal seen in 3.1% of patients. This drug was recently approved for class II and class III PAH in the United States.

The phosphodiesterase inhibitor sildenafil also is now approved for the treatment of all classes of PAH in a dosage of 20 mg three times daily. The drug was evaluated in a double-blind study that randomized 278 patients (mean age 50 years) to placebo or 20, 40, or 80 mg three times daily for 12 weeks.

Improvements were seen in the 6-minute walk test in all groups, with placebo-corrected treatment effects being +13%, +13.3%, and +14.7% in the 20-, 40-, and 80-mg groups, respectively. The incidence of clinical worsening did not differ significantly between the placebo and sildenafil groups. Side effects included flushing, dyspepsia, and diarrhea.

In summarizing the treatment options, the authors noted that for patients in functional class II, the only current recommended drugs are sildenafil and subcutaneous and intravenous treprostinil, and suggested that sildenafil may be the first choice for most patients because of ease of administration and relative efficacy.

For patients in functional class III, five drugs are available: bosentan, sildenafil, intravenous epoprostenol, inhaled iloprost, and subcutaneous or intravenous treprostinil. For those with early class III disease, oral bosentan or sildenafil may be used, with the choice reflecting relative toxicities. For patients with more advanced disease, prostanoid therapy may be needed.

All the available agents are approved for patients with class IV PAH. However, the authors wrote, “[we] strongly encourage IV epoprostenol as the treatment of choice for these most critically ill patients. IV epoprostenol has a rapid and predictable onset of action, and most experts are familiar with how to titrate this drug in the acute setting.”

SAN FRANCISCO — Some patients awaiting heart transplantation are as likely to remain alive for 2 years as are those who get transplanted hearts, an outcome that raises the question of whether better risk-stratification methods would keep some patients from being wait-listed in the first place, Dr. Katherine Lietz said at the annual meeting of the International Society for Heart and Lung Transplantation.

In a retrospective study of newly wait-listed patients in the U.S. from 1990 to 2005, Dr. Lietz and her colleague found that the odds of being alive 1 year later or having received a heart transplant jumped from 49% to 69% for patients classified as United Network for Organ Sharing (UNOS) status 1, and improved from 81% to 89% for UNOS status 2 patients.

The probability of wait-listed patients undergoing heart transplantation within 1 year barely changed during that time span. For status 2 patients, the odds of being transplanted within 1 year decreased from 53% in 1990–1994 to 49% in 2000–2005. For status 1 patients, the odds of being transplanted within 1 year crept from 85% to 87%, and the probability of remaining alive on the waiting list for 1 year increased from 17% in 1990–1994 to 40% in 2000–2005.

The improvements seem to be attributable to better medical and device therapies for advanced heart failure, which are keeping patients alive longer on transplant waiting lists, Dr. Lietz said. UNOS status 1 includes the sickest patients who are on device or mechanical support or continuous infusion with IV inotropes. The number of status 1 patients on heart transplant waiting lists increased from 836 in 1990 to 1,159 in 2005, while the number of status 2 patients on a waiting list decreased from 2,612 in 1992 to 1,147 in 2005. Today, the two groups are nearly equally represented on the waiting lists, reported the investigators, of Georgetown University, Washington.

For status 2 patients, the chances of being alive after 2 years on the waiting list increased from 65% in 1990–1994 to 81% in 2000–2005. That 81% survival rate approaches the current 85% survival rate for patients undergoing heart transplantation. Statistical modeling suggests that 2-year survival for patients added to waiting lists today as status 2 would be equivalent to that of patients undergoing heart transplantation, Dr. Lietz observed.

“That raises the question of whether early listing is justified in some of these patients,” she said.

Status 2 patients are a heterogeneous group, however. In the study, 20% died within 2 years of wait-listing, and another 20% were upgraded to status 1. On the other hand, 1,701 status 2 patients were alive more than 5 years after being wait-listed, and 261 patients were alive after 10 years on the list.

“We need better methods of risk-stratifying them, as early listing may not be justified in all these patients,” Dr. Lietz said.

A physician in the audience suggested that what might help more than better risk stratification at the time of wait-listing is better recognition of “triggers” that should prompt reclassification of patients on the list. These might include status 2 patients whose tolerance to β-blocker therapy decreases, or those who develop a creatinine level greater than 1 mg/dL, she said.

Among the wait-listed status 1 patients, 39% died within 2 months. In this very high-risk group, few patients were supported with mechanical devices. The lack of an implantable cardioverter defibrillator (ICD) was significantly associated with poorer outcomes, “perhaps confirming the role of ICD as a bridge to transplantation in these patients,” Dr. Lietz said. “For [status 1] patients who are very sick with signs of severe pump failure, use of mechanical circulatory support should be considered,” especially if the anticipated wait before transplantation exceeds 2 months because of the patient's blood type, body size, or other factors.

SAN FRANCISCO — Some patients awaiting heart transplantation are as likely to remain alive for 2 years as are those who get transplanted hearts, an outcome that raises the question of whether better risk-stratification methods would keep some patients from being wait-listed in the first place, Dr. Katherine Lietz said at the annual meeting of the International Society for Heart and Lung Transplantation.

In a retrospective study of newly wait-listed patients in the U.S. from 1990 to 2005, Dr. Lietz and her colleague found that the odds of being alive 1 year later or having received a heart transplant jumped from 49% to 69% for patients classified as United Network for Organ Sharing (UNOS) status 1, and improved from 81% to 89% for UNOS status 2 patients.

The probability of wait-listed patients undergoing heart transplantation within 1 year barely changed during that time span. For status 2 patients, the odds of being transplanted within 1 year decreased from 53% in 1990–1994 to 49% in 2000–2005. For status 1 patients, the odds of being transplanted within 1 year crept from 85% to 87%, and the probability of remaining alive on the waiting list for 1 year increased from 17% in 1990–1994 to 40% in 2000–2005.

The improvements seem to be attributable to better medical and device therapies for advanced heart failure, which are keeping patients alive longer on transplant waiting lists, Dr. Lietz said. UNOS status 1 includes the sickest patients who are on device or mechanical support or continuous infusion with IV inotropes. The number of status 1 patients on heart transplant waiting lists increased from 836 in 1990 to 1,159 in 2005, while the number of status 2 patients on a waiting list decreased from 2,612 in 1992 to 1,147 in 2005. Today, the two groups are nearly equally represented on the waiting lists, reported the investigators, of Georgetown University, Washington.

For status 2 patients, the chances of being alive after 2 years on the waiting list increased from 65% in 1990–1994 to 81% in 2000–2005. That 81% survival rate approaches the current 85% survival rate for patients undergoing heart transplantation. Statistical modeling suggests that 2-year survival for patients added to waiting lists today as status 2 would be equivalent to that of patients undergoing heart transplantation, Dr. Lietz observed.

“That raises the question of whether early listing is justified in some of these patients,” she said.

Status 2 patients are a heterogeneous group, however. In the study, 20% died within 2 years of wait-listing, and another 20% were upgraded to status 1. On the other hand, 1,701 status 2 patients were alive more than 5 years after being wait-listed, and 261 patients were alive after 10 years on the list.

“We need better methods of risk-stratifying them, as early listing may not be justified in all these patients,” Dr. Lietz said.

A physician in the audience suggested that what might help more than better risk stratification at the time of wait-listing is better recognition of “triggers” that should prompt reclassification of patients on the list. These might include status 2 patients whose tolerance to β-blocker therapy decreases, or those who develop a creatinine level greater than 1 mg/dL, she said.

Among the wait-listed status 1 patients, 39% died within 2 months. In this very high-risk group, few patients were supported with mechanical devices. The lack of an implantable cardioverter defibrillator (ICD) was significantly associated with poorer outcomes, “perhaps confirming the role of ICD as a bridge to transplantation in these patients,” Dr. Lietz said. “For [status 1] patients who are very sick with signs of severe pump failure, use of mechanical circulatory support should be considered,” especially if the anticipated wait before transplantation exceeds 2 months because of the patient's blood type, body size, or other factors.

SAN FRANCISCO — Some patients awaiting heart transplantation are as likely to remain alive for 2 years as are those who get transplanted hearts, an outcome that raises the question of whether better risk-stratification methods would keep some patients from being wait-listed in the first place, Dr. Katherine Lietz said at the annual meeting of the International Society for Heart and Lung Transplantation.

In a retrospective study of newly wait-listed patients in the U.S. from 1990 to 2005, Dr. Lietz and her colleague found that the odds of being alive 1 year later or having received a heart transplant jumped from 49% to 69% for patients classified as United Network for Organ Sharing (UNOS) status 1, and improved from 81% to 89% for UNOS status 2 patients.

The probability of wait-listed patients undergoing heart transplantation within 1 year barely changed during that time span. For status 2 patients, the odds of being transplanted within 1 year decreased from 53% in 1990–1994 to 49% in 2000–2005. For status 1 patients, the odds of being transplanted within 1 year crept from 85% to 87%, and the probability of remaining alive on the waiting list for 1 year increased from 17% in 1990–1994 to 40% in 2000–2005.

The improvements seem to be attributable to better medical and device therapies for advanced heart failure, which are keeping patients alive longer on transplant waiting lists, Dr. Lietz said. UNOS status 1 includes the sickest patients who are on device or mechanical support or continuous infusion with IV inotropes. The number of status 1 patients on heart transplant waiting lists increased from 836 in 1990 to 1,159 in 2005, while the number of status 2 patients on a waiting list decreased from 2,612 in 1992 to 1,147 in 2005. Today, the two groups are nearly equally represented on the waiting lists, reported the investigators, of Georgetown University, Washington.

For status 2 patients, the chances of being alive after 2 years on the waiting list increased from 65% in 1990–1994 to 81% in 2000–2005. That 81% survival rate approaches the current 85% survival rate for patients undergoing heart transplantation. Statistical modeling suggests that 2-year survival for patients added to waiting lists today as status 2 would be equivalent to that of patients undergoing heart transplantation, Dr. Lietz observed.

“That raises the question of whether early listing is justified in some of these patients,” she said.

Status 2 patients are a heterogeneous group, however. In the study, 20% died within 2 years of wait-listing, and another 20% were upgraded to status 1. On the other hand, 1,701 status 2 patients were alive more than 5 years after being wait-listed, and 261 patients were alive after 10 years on the list.

“We need better methods of risk-stratifying them, as early listing may not be justified in all these patients,” Dr. Lietz said.

A physician in the audience suggested that what might help more than better risk stratification at the time of wait-listing is better recognition of “triggers” that should prompt reclassification of patients on the list. These might include status 2 patients whose tolerance to β-blocker therapy decreases, or those who develop a creatinine level greater than 1 mg/dL, she said.

Among the wait-listed status 1 patients, 39% died within 2 months. In this very high-risk group, few patients were supported with mechanical devices. The lack of an implantable cardioverter defibrillator (ICD) was significantly associated with poorer outcomes, “perhaps confirming the role of ICD as a bridge to transplantation in these patients,” Dr. Lietz said. “For [status 1] patients who are very sick with signs of severe pump failure, use of mechanical circulatory support should be considered,” especially if the anticipated wait before transplantation exceeds 2 months because of the patient's blood type, body size, or other factors.

SAN FRANCISCO — Patients over the age of 70 do almost as well after heart transplants as younger recipients, unless they are infected with hepatitis C, according to a poster presentation by Dr. Jignesh K. Patel at the American Transplant Congress.

In a retrospective analysis, Dr. Patel and colleagues from the University of California, Los Angeles, compared 25 heart recipients aged 70-75 years (mean of 72 years) with 246 younger patients (mean of 56 years).

There were no differences between the groups in early cardiac allograft vasculopathy or in the percentage of patients being treated for rejection during the first year.

The younger patients did have a significantly higher 5-year survival rate than did the older patients–80% vs. 64%. However, when the investigators excluded from the analysis all patients with hepatitis C at the time of transplant and those receiving organs from hepatitis C-positive donors, the difference in 5-year survival failed to reach statistical significance. Three of the nine patients who died in the older age group had hepatitis C prior to transplantation.

Since all the older patients were classified as status 2, indicating relatively low-risk patients who did not require intravenous medications, the investigators selected only status 2 recipients for the control group.

SAN FRANCISCO — Patients over the age of 70 do almost as well after heart transplants as younger recipients, unless they are infected with hepatitis C, according to a poster presentation by Dr. Jignesh K. Patel at the American Transplant Congress.

In a retrospective analysis, Dr. Patel and colleagues from the University of California, Los Angeles, compared 25 heart recipients aged 70-75 years (mean of 72 years) with 246 younger patients (mean of 56 years).

There were no differences between the groups in early cardiac allograft vasculopathy or in the percentage of patients being treated for rejection during the first year.

The younger patients did have a significantly higher 5-year survival rate than did the older patients–80% vs. 64%. However, when the investigators excluded from the analysis all patients with hepatitis C at the time of transplant and those receiving organs from hepatitis C-positive donors, the difference in 5-year survival failed to reach statistical significance. Three of the nine patients who died in the older age group had hepatitis C prior to transplantation.

Since all the older patients were classified as status 2, indicating relatively low-risk patients who did not require intravenous medications, the investigators selected only status 2 recipients for the control group.

SAN FRANCISCO — Patients over the age of 70 do almost as well after heart transplants as younger recipients, unless they are infected with hepatitis C, according to a poster presentation by Dr. Jignesh K. Patel at the American Transplant Congress.

In a retrospective analysis, Dr. Patel and colleagues from the University of California, Los Angeles, compared 25 heart recipients aged 70-75 years (mean of 72 years) with 246 younger patients (mean of 56 years).

There were no differences between the groups in early cardiac allograft vasculopathy or in the percentage of patients being treated for rejection during the first year.

The younger patients did have a significantly higher 5-year survival rate than did the older patients–80% vs. 64%. However, when the investigators excluded from the analysis all patients with hepatitis C at the time of transplant and those receiving organs from hepatitis C-positive donors, the difference in 5-year survival failed to reach statistical significance. Three of the nine patients who died in the older age group had hepatitis C prior to transplantation.

Since all the older patients were classified as status 2, indicating relatively low-risk patients who did not require intravenous medications, the investigators selected only status 2 recipients for the control group.

NEW ORLEANS — Angiotensin receptor blockers were associated with significantly greater risk of worsening renal function than were angiotentin-converting enzyme inhibitors in patients with systolic heart failure in a meta-analysis of all seven head-to-head comparative randomized, controlled, clinical trials, Dr. Rachid Lakhdar reported at the annual meeting of the American College of Cardiology.

“The ARBs are trying to make it as first-line drugs. The most recent guidelines put them as a class IIa indication, allowing them as first-line therapy in patients with mild to moderate heart failure and reduced left ventricular function,” he said in an interview.

“Our conclusion from the meta-analysis is maybe that's not such a good idea, and ARBs should continue to be second line, to be used when ACE inhibitors are contraindicated,” he continued.

The meta-analysis involved 20,143 systolic dysfunction heart failure patients who were randomized to an ACE inhibitor or ARB. Among the studies they were drawn from were the Valsartan in Acute Myocardial Infarction Trial (VALIANT), the first and second Evaluation of Losartan in the Elderly (ELITE I and II), the Optimal Therapy in Myocardial Infarction With the Angiotensin II Antagonist Losartan (OPTIMAAL) trial, and the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study.

Carried out without commercial support, the meta-analysis clearly showed that overall side effects were significantly less frequent with ARBs. Indeed, the combined incidence of cough, angioedema, hyperkalemia, hypotension, and worsening renal function was 42% less with ARB therapy than with ACE inhibitor therapy in patients with systolic heart failure. However, the relative risk of worsening renal function was 60% greater with angiotensin receptor blockers, according to Dr. Lakhdar, a third-year resident at the Henry Ford Hospital System, Detroit.

The ARB and ACE inhibitor arms were evenly matched in terms of diuretic therapy and other potential confounders.

“This is a new observation that certainly needs more research, including a prospective study to pinpoint the pathophysiology as to why ARBs are more likely to worsen renal function,” the physician added.

Discussant Dr. Lynne E. Wagoner predicted that guideline-writing committees are going to have to pay attention to the new meta-analysis.

“Cough is the major reason ACE inhibitors are discontinued. Often that cough is not severe and certainly is not life threatening,” said Dr. Wagoner, medical director of the cardiac transplantation division at the University of Cincinnati.

“However, the risk of worsening renal function is potentially life threatening and therefore should be stressed in guideline recommendations. ARBs should remain second-line therapy behind ACE inhibitors as a result of these findings,” he continued.

NEW ORLEANS — Angiotensin receptor blockers were associated with significantly greater risk of worsening renal function than were angiotentin-converting enzyme inhibitors in patients with systolic heart failure in a meta-analysis of all seven head-to-head comparative randomized, controlled, clinical trials, Dr. Rachid Lakhdar reported at the annual meeting of the American College of Cardiology.

“The ARBs are trying to make it as first-line drugs. The most recent guidelines put them as a class IIa indication, allowing them as first-line therapy in patients with mild to moderate heart failure and reduced left ventricular function,” he said in an interview.

“Our conclusion from the meta-analysis is maybe that's not such a good idea, and ARBs should continue to be second line, to be used when ACE inhibitors are contraindicated,” he continued.

The meta-analysis involved 20,143 systolic dysfunction heart failure patients who were randomized to an ACE inhibitor or ARB. Among the studies they were drawn from were the Valsartan in Acute Myocardial Infarction Trial (VALIANT), the first and second Evaluation of Losartan in the Elderly (ELITE I and II), the Optimal Therapy in Myocardial Infarction With the Angiotensin II Antagonist Losartan (OPTIMAAL) trial, and the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study.

Carried out without commercial support, the meta-analysis clearly showed that overall side effects were significantly less frequent with ARBs. Indeed, the combined incidence of cough, angioedema, hyperkalemia, hypotension, and worsening renal function was 42% less with ARB therapy than with ACE inhibitor therapy in patients with systolic heart failure. However, the relative risk of worsening renal function was 60% greater with angiotensin receptor blockers, according to Dr. Lakhdar, a third-year resident at the Henry Ford Hospital System, Detroit.

The ARB and ACE inhibitor arms were evenly matched in terms of diuretic therapy and other potential confounders.

“This is a new observation that certainly needs more research, including a prospective study to pinpoint the pathophysiology as to why ARBs are more likely to worsen renal function,” the physician added.

Discussant Dr. Lynne E. Wagoner predicted that guideline-writing committees are going to have to pay attention to the new meta-analysis.

“Cough is the major reason ACE inhibitors are discontinued. Often that cough is not severe and certainly is not life threatening,” said Dr. Wagoner, medical director of the cardiac transplantation division at the University of Cincinnati.

“However, the risk of worsening renal function is potentially life threatening and therefore should be stressed in guideline recommendations. ARBs should remain second-line therapy behind ACE inhibitors as a result of these findings,” he continued.

NEW ORLEANS — Angiotensin receptor blockers were associated with significantly greater risk of worsening renal function than were angiotentin-converting enzyme inhibitors in patients with systolic heart failure in a meta-analysis of all seven head-to-head comparative randomized, controlled, clinical trials, Dr. Rachid Lakhdar reported at the annual meeting of the American College of Cardiology.

“The ARBs are trying to make it as first-line drugs. The most recent guidelines put them as a class IIa indication, allowing them as first-line therapy in patients with mild to moderate heart failure and reduced left ventricular function,” he said in an interview.

“Our conclusion from the meta-analysis is maybe that's not such a good idea, and ARBs should continue to be second line, to be used when ACE inhibitors are contraindicated,” he continued.

The meta-analysis involved 20,143 systolic dysfunction heart failure patients who were randomized to an ACE inhibitor or ARB. Among the studies they were drawn from were the Valsartan in Acute Myocardial Infarction Trial (VALIANT), the first and second Evaluation of Losartan in the Elderly (ELITE I and II), the Optimal Therapy in Myocardial Infarction With the Angiotensin II Antagonist Losartan (OPTIMAAL) trial, and the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) study.

Carried out without commercial support, the meta-analysis clearly showed that overall side effects were significantly less frequent with ARBs. Indeed, the combined incidence of cough, angioedema, hyperkalemia, hypotension, and worsening renal function was 42% less with ARB therapy than with ACE inhibitor therapy in patients with systolic heart failure. However, the relative risk of worsening renal function was 60% greater with angiotensin receptor blockers, according to Dr. Lakhdar, a third-year resident at the Henry Ford Hospital System, Detroit.

The ARB and ACE inhibitor arms were evenly matched in terms of diuretic therapy and other potential confounders.

“This is a new observation that certainly needs more research, including a prospective study to pinpoint the pathophysiology as to why ARBs are more likely to worsen renal function,” the physician added.

Discussant Dr. Lynne E. Wagoner predicted that guideline-writing committees are going to have to pay attention to the new meta-analysis.

“Cough is the major reason ACE inhibitors are discontinued. Often that cough is not severe and certainly is not life threatening,” said Dr. Wagoner, medical director of the cardiac transplantation division at the University of Cincinnati.

“However, the risk of worsening renal function is potentially life threatening and therefore should be stressed in guideline recommendations. ARBs should remain second-line therapy behind ACE inhibitors as a result of these findings,” he continued.

NEW ORLEANS — Depression is common among patients with heart failure and is independently associated with poor outcomes, Dr. Aldo P. Maggioni said at the annual meeting of the American College of Cardiology.

He presented a retrospective study involving 18,623 patients with heart failure over age 60 identified in an administrative health care database covering two regions of Italy. At entry, 13% were being treated for depression.

In a multivariate logistic regression analysis, comorbid depression was independently associated with a highly significant 28% increased risk of all-cause mortality at 1 year, compared with the risk in heart failure patients not treated for depression.

Depression also was associated with an adjusted 36% increased risk of a 1-year composite end point consisting of MI, stroke, or transient ischemic attack, along with an 18% increase in all-cause hospitalization. However, the risk of rehospitalization for heart failure was no greater in patients treated for depression than in those who weren't, according to Dr. Maggioni, a cardiologist at the Mario Negri Research Consortium South, Santa Maria Imbaro, Italy.

He noted that while the adverse effect of comorbid depression on outcomes in patients with coronary artery disease is well established, there is much less evidence regarding the mood disorder's effect in patients with heart failure. Most previous studies have been quite small.

The strength of the new Italian study is its very large numbers. Its weakness is that there was no systematic screening for depression, so it's entirely possible the “nondepressed” comparator group included a fair number of heart failure patients with undiagnosed and untreated depression. Regardless, Dr. Maggioni said, the study conclusion was essentially the same as in the much smaller studies in which heart failure patients were screened for depression by questionnaire or interview: Depression is associated with poor outcomes in heart failure.

The mean age of participants in this study was 78 years. Patients treated for comorbid depression were significantly older than those who weren't. Sixty-nine percent were women, compared with 58% of heart failure patients not treated for depression.

Patients with depression also were significantly more likely to have a baseline history of stroke, transient ischemic attack, cancer, and chronic obstructive pulmonary disease.

Dr. Maggioni offered three potential explanations for the worse clinical outcomes in heart failure patients treated for depression. One possibility is that some antidepressant medications might have adverse effects in this population. Another is that depression exacerbates the underlying pathophysiology of heart failure, which is plausible in light of the fact that both conditions involve increased sympathetic nervous system activity, platelet activation, and systemic inflammation. But the most likely explanation for the association, in Dr. Maggioni's view, is that depressed patients have less social support and are less adherent to their cardiovascular therapy.

The big unanswered question is whether treatment of depression improves heart failure outcomes, he said. There are no data, and a definitive randomized clinical trial would need to be very large.

“You need the numbers. If you're testing a new drug, just to see a 15% relative difference in mortality, you need perhaps 7,000 patients,” Dr. Maggioni noted in an interview.

Session Chair Douglas P. Zipes called the Italian report linking depression to worse outcomes in heart failure “a very important observation” regarding an issue that doesn't receive sufficient attention from nonpsychiatrists.

“I think we tend to focus on more tangible issues, such as which coronary artery is occluded [and] the warfarin dose. My impression is that issues such as depression, sexual activity, and support groups aren't discussed at length–and they should be,” said Dr. Zipes, Distinguished Professor of Medicine, Pharmacology, and Toxicology at Indiana University, Indianapolis.

Depressed patients have less social support and are less adherent to their cardiovascular therapy. DR. MAGGIONI

NEW ORLEANS — Depression is common among patients with heart failure and is independently associated with poor outcomes, Dr. Aldo P. Maggioni said at the annual meeting of the American College of Cardiology.

He presented a retrospective study involving 18,623 patients with heart failure over age 60 identified in an administrative health care database covering two regions of Italy. At entry, 13% were being treated for depression.

In a multivariate logistic regression analysis, comorbid depression was independently associated with a highly significant 28% increased risk of all-cause mortality at 1 year, compared with the risk in heart failure patients not treated for depression.

Depression also was associated with an adjusted 36% increased risk of a 1-year composite end point consisting of MI, stroke, or transient ischemic attack, along with an 18% increase in all-cause hospitalization. However, the risk of rehospitalization for heart failure was no greater in patients treated for depression than in those who weren't, according to Dr. Maggioni, a cardiologist at the Mario Negri Research Consortium South, Santa Maria Imbaro, Italy.

He noted that while the adverse effect of comorbid depression on outcomes in patients with coronary artery disease is well established, there is much less evidence regarding the mood disorder's effect in patients with heart failure. Most previous studies have been quite small.

The strength of the new Italian study is its very large numbers. Its weakness is that there was no systematic screening for depression, so it's entirely possible the “nondepressed” comparator group included a fair number of heart failure patients with undiagnosed and untreated depression. Regardless, Dr. Maggioni said, the study conclusion was essentially the same as in the much smaller studies in which heart failure patients were screened for depression by questionnaire or interview: Depression is associated with poor outcomes in heart failure.

The mean age of participants in this study was 78 years. Patients treated for comorbid depression were significantly older than those who weren't. Sixty-nine percent were women, compared with 58% of heart failure patients not treated for depression.

Patients with depression also were significantly more likely to have a baseline history of stroke, transient ischemic attack, cancer, and chronic obstructive pulmonary disease.

Dr. Maggioni offered three potential explanations for the worse clinical outcomes in heart failure patients treated for depression. One possibility is that some antidepressant medications might have adverse effects in this population. Another is that depression exacerbates the underlying pathophysiology of heart failure, which is plausible in light of the fact that both conditions involve increased sympathetic nervous system activity, platelet activation, and systemic inflammation. But the most likely explanation for the association, in Dr. Maggioni's view, is that depressed patients have less social support and are less adherent to their cardiovascular therapy.

The big unanswered question is whether treatment of depression improves heart failure outcomes, he said. There are no data, and a definitive randomized clinical trial would need to be very large.

“You need the numbers. If you're testing a new drug, just to see a 15% relative difference in mortality, you need perhaps 7,000 patients,” Dr. Maggioni noted in an interview.

Session Chair Douglas P. Zipes called the Italian report linking depression to worse outcomes in heart failure “a very important observation” regarding an issue that doesn't receive sufficient attention from nonpsychiatrists.

“I think we tend to focus on more tangible issues, such as which coronary artery is occluded [and] the warfarin dose. My impression is that issues such as depression, sexual activity, and support groups aren't discussed at length–and they should be,” said Dr. Zipes, Distinguished Professor of Medicine, Pharmacology, and Toxicology at Indiana University, Indianapolis.

Depressed patients have less social support and are less adherent to their cardiovascular therapy. DR. MAGGIONI

NEW ORLEANS — Depression is common among patients with heart failure and is independently associated with poor outcomes, Dr. Aldo P. Maggioni said at the annual meeting of the American College of Cardiology.

He presented a retrospective study involving 18,623 patients with heart failure over age 60 identified in an administrative health care database covering two regions of Italy. At entry, 13% were being treated for depression.

In a multivariate logistic regression analysis, comorbid depression was independently associated with a highly significant 28% increased risk of all-cause mortality at 1 year, compared with the risk in heart failure patients not treated for depression.

Depression also was associated with an adjusted 36% increased risk of a 1-year composite end point consisting of MI, stroke, or transient ischemic attack, along with an 18% increase in all-cause hospitalization. However, the risk of rehospitalization for heart failure was no greater in patients treated for depression than in those who weren't, according to Dr. Maggioni, a cardiologist at the Mario Negri Research Consortium South, Santa Maria Imbaro, Italy.

He noted that while the adverse effect of comorbid depression on outcomes in patients with coronary artery disease is well established, there is much less evidence regarding the mood disorder's effect in patients with heart failure. Most previous studies have been quite small.

The strength of the new Italian study is its very large numbers. Its weakness is that there was no systematic screening for depression, so it's entirely possible the “nondepressed” comparator group included a fair number of heart failure patients with undiagnosed and untreated depression. Regardless, Dr. Maggioni said, the study conclusion was essentially the same as in the much smaller studies in which heart failure patients were screened for depression by questionnaire or interview: Depression is associated with poor outcomes in heart failure.

The mean age of participants in this study was 78 years. Patients treated for comorbid depression were significantly older than those who weren't. Sixty-nine percent were women, compared with 58% of heart failure patients not treated for depression.

Patients with depression also were significantly more likely to have a baseline history of stroke, transient ischemic attack, cancer, and chronic obstructive pulmonary disease.

Dr. Maggioni offered three potential explanations for the worse clinical outcomes in heart failure patients treated for depression. One possibility is that some antidepressant medications might have adverse effects in this population. Another is that depression exacerbates the underlying pathophysiology of heart failure, which is plausible in light of the fact that both conditions involve increased sympathetic nervous system activity, platelet activation, and systemic inflammation. But the most likely explanation for the association, in Dr. Maggioni's view, is that depressed patients have less social support and are less adherent to their cardiovascular therapy.

The big unanswered question is whether treatment of depression improves heart failure outcomes, he said. There are no data, and a definitive randomized clinical trial would need to be very large.

“You need the numbers. If you're testing a new drug, just to see a 15% relative difference in mortality, you need perhaps 7,000 patients,” Dr. Maggioni noted in an interview.

Session Chair Douglas P. Zipes called the Italian report linking depression to worse outcomes in heart failure “a very important observation” regarding an issue that doesn't receive sufficient attention from nonpsychiatrists.

“I think we tend to focus on more tangible issues, such as which coronary artery is occluded [and] the warfarin dose. My impression is that issues such as depression, sexual activity, and support groups aren't discussed at length–and they should be,” said Dr. Zipes, Distinguished Professor of Medicine, Pharmacology, and Toxicology at Indiana University, Indianapolis.

Depressed patients have less social support and are less adherent to their cardiovascular therapy. DR. MAGGIONI

NEW ORLEANS — A new-generation heart pump was at least as effective as prior models and was also substantially safer, causing fewer deaths and complications in a study with 133 patients. The new unit is also one-seventh the size of the existing model, and is silent.

These results, in a study that assessed the HeartMate II assist device as a bridge to heart transplant, “give us an encouraging look to the future of the primary indication for this treatment,” as destination therapy for patients who are not eligible for a heart transplant, Dr. Leslie W. Miller said at the annual meeting of the American College of Cardiology. A study of the device as destination therapy that's designed to include 200 patients had enrolled 151 patients by late January 2007.

Despite the limitations of the current results based on the indication studied, “the data are a benchmark and branch point in the field of mechanical support. This represents an amazing accomplishment. It is a device for the future,” said Dr. Miller in a conference call following his report at the meeting. The new results “will significantly impact the use of this technology.”

With the new device, “there's a great future for our patients with severe heart failure,” said Dr. Christopher M. O'Connor, director of the heart failure and transplant program at Duke University, Durham, N.C., at the meeting.

The HeartMate II is made by Thoratec Corp., which markets the HeartMate XVE, the current, standard left ventricular assist device. Dr. Miller is a consultant to and has received honoraria and research support from Thoratec.

HeartMate II produces continuous blood flow, unlike the pulsatile pumps of prior-generation devices. In addition to being substantially smaller, the new pump is about 75% lighter than the XVE model, with a 40% smaller percutaneous lead and just one moving part, which is expected to result in much greater durability. The device should last 5–10 years in most patients, said Dr. Miller, chief of the integrated divisions of cardiology at Georgetown University, Washington.

The device was tested at 26 sites in the United States during March 2005-March 2006. The study was not randomized, and instead compared the new unit to an objective performance criterion based on the historic performance of three prior assist devices. The derived criterion stipulated that at least 75% of patients who received the new device had to survive either to heart transplant or for at least 180 days while remaining transplant eligible.

The enrolled patients were 18–69 years old, and were all listed as status 1A or 1B for a heart transplant. Their average left ventricular ejection fraction was 16%. Because of the device's smaller size, the entry criteria were expanded to include smaller patients; 21% of the patients were women, including seven women with a body surface area of less than 1.5 m2, a size that was previously unable to accommodate an implanted assist device.

During follow-up, 100 patients (75%) either went on to receive a heart transplant (68 patients), survived for more than 180 days while awaiting a transplant (29), or recovered substantially and had the device explanted (3), which meant that the results met the study's primary end point. The overall average duration of device support was 168 days. Among the 29 patients who went longer than 180 days without a transplant, the average time on the device was 360 days, with one patient maintained for 600 days. Among the remaining patients, 25 died within 180 days.

Actuarial 6-month survival for all 133 patients was 75%, and 68% survived for 1 year. Most of the deaths occurred prior to hospital discharge, with only three patients dying during the period 4.5–12 months after their devices were placed. The most common causes of death were sepsis, stroke, and multiorgan failure. The most common adverse events were bleeding (41 patients), infections (37), ventricular arrhythmias (32), and renal failure (18). Five patients had to have their devices replaced, with one death linked to explantation.

While on the device, patients showed dramatic improvements in their heart failure status, their 6-minute walk distance, and their quality of life.

“What's most impressive was the survival rate after 4.5 months,” when only three patients died, said Dr. Miller. In contrast, in the landmark, pivotal trial of the XVE model, the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial, 52% of patients survived for 1 year and 25% survived for 2 years. When deaths immediately after surgery in the new trial are discounted, survival with the HeartMate II model looks to be about 20% better, in absolute terms, compared with the XVE model.

“If we can provide a 20% absolute difference in mortality [with HeartMate II], that would outdistance any medical therapy we have and it would be a tremendous change,” Dr. Miller said during the conference call.

Another notable result was the units' reliability, with only five devices needing removal and only two developing thrombosis. “That's incredible performance,” Dr. Miller said.

The much smaller size of the new model is another important factor. “You need one-seventh of the surgical dissection to create the pocket where the pump goes. That probably accounts for the reduced bleeding, and it's technically easier. My surgeons are looking forward to this.

“I don't honestly see any downside to the data. We saw a safety and efficacy profile that beat anything that's been published. We met the end point with success across the board,” Dr. Miller said.

NEW ORLEANS — A new-generation heart pump was at least as effective as prior models and was also substantially safer, causing fewer deaths and complications in a study with 133 patients. The new unit is also one-seventh the size of the existing model, and is silent.

These results, in a study that assessed the HeartMate II assist device as a bridge to heart transplant, “give us an encouraging look to the future of the primary indication for this treatment,” as destination therapy for patients who are not eligible for a heart transplant, Dr. Leslie W. Miller said at the annual meeting of the American College of Cardiology. A study of the device as destination therapy that's designed to include 200 patients had enrolled 151 patients by late January 2007.

Despite the limitations of the current results based on the indication studied, “the data are a benchmark and branch point in the field of mechanical support. This represents an amazing accomplishment. It is a device for the future,” said Dr. Miller in a conference call following his report at the meeting. The new results “will significantly impact the use of this technology.”

With the new device, “there's a great future for our patients with severe heart failure,” said Dr. Christopher M. O'Connor, director of the heart failure and transplant program at Duke University, Durham, N.C., at the meeting.

The HeartMate II is made by Thoratec Corp., which markets the HeartMate XVE, the current, standard left ventricular assist device. Dr. Miller is a consultant to and has received honoraria and research support from Thoratec.

HeartMate II produces continuous blood flow, unlike the pulsatile pumps of prior-generation devices. In addition to being substantially smaller, the new pump is about 75% lighter than the XVE model, with a 40% smaller percutaneous lead and just one moving part, which is expected to result in much greater durability. The device should last 5–10 years in most patients, said Dr. Miller, chief of the integrated divisions of cardiology at Georgetown University, Washington.

The device was tested at 26 sites in the United States during March 2005-March 2006. The study was not randomized, and instead compared the new unit to an objective performance criterion based on the historic performance of three prior assist devices. The derived criterion stipulated that at least 75% of patients who received the new device had to survive either to heart transplant or for at least 180 days while remaining transplant eligible.

The enrolled patients were 18–69 years old, and were all listed as status 1A or 1B for a heart transplant. Their average left ventricular ejection fraction was 16%. Because of the device's smaller size, the entry criteria were expanded to include smaller patients; 21% of the patients were women, including seven women with a body surface area of less than 1.5 m2, a size that was previously unable to accommodate an implanted assist device.

During follow-up, 100 patients (75%) either went on to receive a heart transplant (68 patients), survived for more than 180 days while awaiting a transplant (29), or recovered substantially and had the device explanted (3), which meant that the results met the study's primary end point. The overall average duration of device support was 168 days. Among the 29 patients who went longer than 180 days without a transplant, the average time on the device was 360 days, with one patient maintained for 600 days. Among the remaining patients, 25 died within 180 days.

Actuarial 6-month survival for all 133 patients was 75%, and 68% survived for 1 year. Most of the deaths occurred prior to hospital discharge, with only three patients dying during the period 4.5–12 months after their devices were placed. The most common causes of death were sepsis, stroke, and multiorgan failure. The most common adverse events were bleeding (41 patients), infections (37), ventricular arrhythmias (32), and renal failure (18). Five patients had to have their devices replaced, with one death linked to explantation.

While on the device, patients showed dramatic improvements in their heart failure status, their 6-minute walk distance, and their quality of life.

“What's most impressive was the survival rate after 4.5 months,” when only three patients died, said Dr. Miller. In contrast, in the landmark, pivotal trial of the XVE model, the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial, 52% of patients survived for 1 year and 25% survived for 2 years. When deaths immediately after surgery in the new trial are discounted, survival with the HeartMate II model looks to be about 20% better, in absolute terms, compared with the XVE model.

“If we can provide a 20% absolute difference in mortality [with HeartMate II], that would outdistance any medical therapy we have and it would be a tremendous change,” Dr. Miller said during the conference call.

Another notable result was the units' reliability, with only five devices needing removal and only two developing thrombosis. “That's incredible performance,” Dr. Miller said.

The much smaller size of the new model is another important factor. “You need one-seventh of the surgical dissection to create the pocket where the pump goes. That probably accounts for the reduced bleeding, and it's technically easier. My surgeons are looking forward to this.

“I don't honestly see any downside to the data. We saw a safety and efficacy profile that beat anything that's been published. We met the end point with success across the board,” Dr. Miller said.

NEW ORLEANS — A new-generation heart pump was at least as effective as prior models and was also substantially safer, causing fewer deaths and complications in a study with 133 patients. The new unit is also one-seventh the size of the existing model, and is silent.

These results, in a study that assessed the HeartMate II assist device as a bridge to heart transplant, “give us an encouraging look to the future of the primary indication for this treatment,” as destination therapy for patients who are not eligible for a heart transplant, Dr. Leslie W. Miller said at the annual meeting of the American College of Cardiology. A study of the device as destination therapy that's designed to include 200 patients had enrolled 151 patients by late January 2007.

Despite the limitations of the current results based on the indication studied, “the data are a benchmark and branch point in the field of mechanical support. This represents an amazing accomplishment. It is a device for the future,” said Dr. Miller in a conference call following his report at the meeting. The new results “will significantly impact the use of this technology.”

With the new device, “there's a great future for our patients with severe heart failure,” said Dr. Christopher M. O'Connor, director of the heart failure and transplant program at Duke University, Durham, N.C., at the meeting.

The HeartMate II is made by Thoratec Corp., which markets the HeartMate XVE, the current, standard left ventricular assist device. Dr. Miller is a consultant to and has received honoraria and research support from Thoratec.

HeartMate II produces continuous blood flow, unlike the pulsatile pumps of prior-generation devices. In addition to being substantially smaller, the new pump is about 75% lighter than the XVE model, with a 40% smaller percutaneous lead and just one moving part, which is expected to result in much greater durability. The device should last 5–10 years in most patients, said Dr. Miller, chief of the integrated divisions of cardiology at Georgetown University, Washington.

The device was tested at 26 sites in the United States during March 2005-March 2006. The study was not randomized, and instead compared the new unit to an objective performance criterion based on the historic performance of three prior assist devices. The derived criterion stipulated that at least 75% of patients who received the new device had to survive either to heart transplant or for at least 180 days while remaining transplant eligible.

The enrolled patients were 18–69 years old, and were all listed as status 1A or 1B for a heart transplant. Their average left ventricular ejection fraction was 16%. Because of the device's smaller size, the entry criteria were expanded to include smaller patients; 21% of the patients were women, including seven women with a body surface area of less than 1.5 m2, a size that was previously unable to accommodate an implanted assist device.

During follow-up, 100 patients (75%) either went on to receive a heart transplant (68 patients), survived for more than 180 days while awaiting a transplant (29), or recovered substantially and had the device explanted (3), which meant that the results met the study's primary end point. The overall average duration of device support was 168 days. Among the 29 patients who went longer than 180 days without a transplant, the average time on the device was 360 days, with one patient maintained for 600 days. Among the remaining patients, 25 died within 180 days.

Actuarial 6-month survival for all 133 patients was 75%, and 68% survived for 1 year. Most of the deaths occurred prior to hospital discharge, with only three patients dying during the period 4.5–12 months after their devices were placed. The most common causes of death were sepsis, stroke, and multiorgan failure. The most common adverse events were bleeding (41 patients), infections (37), ventricular arrhythmias (32), and renal failure (18). Five patients had to have their devices replaced, with one death linked to explantation.

While on the device, patients showed dramatic improvements in their heart failure status, their 6-minute walk distance, and their quality of life.

“What's most impressive was the survival rate after 4.5 months,” when only three patients died, said Dr. Miller. In contrast, in the landmark, pivotal trial of the XVE model, the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial, 52% of patients survived for 1 year and 25% survived for 2 years. When deaths immediately after surgery in the new trial are discounted, survival with the HeartMate II model looks to be about 20% better, in absolute terms, compared with the XVE model.

“If we can provide a 20% absolute difference in mortality [with HeartMate II], that would outdistance any medical therapy we have and it would be a tremendous change,” Dr. Miller said during the conference call.

Another notable result was the units' reliability, with only five devices needing removal and only two developing thrombosis. “That's incredible performance,” Dr. Miller said.

The much smaller size of the new model is another important factor. “You need one-seventh of the surgical dissection to create the pocket where the pump goes. That probably accounts for the reduced bleeding, and it's technically easier. My surgeons are looking forward to this.

“I don't honestly see any downside to the data. We saw a safety and efficacy profile that beat anything that's been published. We met the end point with success across the board,” Dr. Miller said.

NEW ORLEANS — New results further supported T-wave alternans as a way to identify patients with nonischemic cardiomyopathy who do not need an implantable cardioverter defibrillator.

Findings from a study with 446 patients done in Italy showed that among patients with nonischemic cardiomyopathy and New York Heart Association class II or III heart failure, “patients with a normal TWA [T-wave alternans] test have a very good prognosis and are unlikely to benefit from ICD [implantable cardioverter defibrillator] therapy,” Dr. Gaetano M. De Ferrari said at the annual meeting of the American College of Cardiology.

In contrast, similar patients with an abnormal TWA result had a fourfold increased risk of cardiac death or a life-threatening ventricular arrhythmia during 18–24 months of follow-up, suggesting that these patients are good candidates for an ICD, said Dr. De Ferrari, chief of the cardiac ICU at Hospital San Matteo in Pavia, Italy.

The results from this “methodologically sound, prospective study confirm with high quality what [results from] other studies have shown,” that the predictive value of TWA in patients with nonischemic cardiomyopathy is similar to its predictive value in patients with ischemic cardiomyopathy, said Dr. Theodore Chow, director of electrophysiology research at the Ohio Heart and Vascular Center in Cincinnati. The new findings, in combination with prior results from other studies, “provide a rationale for a careful, prospective evaluation of whether ICD implants are useful in nonischemic patients with normal TWA.”

Until such a trial is done, “I think that most cardiologists will still generally favor placing ICDs based on data from” the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which showed that ICDs significantly cut mortality in all patients with a left ventricular ejection fraction of 35% or less, said Dr. Chow in an interview.

“We need strategies to sort out who gets an ICD. It's not clear why the use of ICDs is so low, but it's hard to picture that it will be solved by having TWA measurement in all patients,” commented Dr. Mariell L. Jessup, professor of medicine and medical director of heart failure and cardiac transplantation at the University of Pennsylvania, Philadelphia.

The T-Wave Alternans in Patients with Heart Failure (ALPHA) study was done at nine centers in Italy, and was funded in part by Boston Scientific, a company that markets an ICD but does not market equipment used for assessing TWA. The equipment used to measure TWA in the ALPHA study was made by Cambridge Heart.

Dr. De Ferrari and his associates screened more than 3,500 patients with heart failure to identify 446 with nonischemic, dilated cardiomyopathy, a left ventricular ejection fraction of 40% or less, New York Heart Association class II or III heart failure, and no other indication for receiving an ICD. TWA testing identified 154 patients with normal readings and 292 patients with an abnormal result.

During follow-up, the incidence of the study's primary end point—cardiac death or development of a life-threatening ventricular arrhythmia—was 10% in the patients with an abnormal TWA and 3% in those with a normal TWA, a statistically significant difference. When adjusted for baseline differences in age, gender, New York Heart Association class, and left ventricular ejection fraction, patients with an abnormal TWA reading at baseline were 3.2-fold more likely to develop the primary end point than were those with a normal TWA result.

“The most important finding” was the negative predictive value of a normal TWA result at baseline, said Dr. De Ferrari. During 18 months of follow-up, 97% of patients with a normal TWA result were free from the primary end point. “Patients with a normal TWA had a very good prognosis and were unlikely to benefit from an ICD,” he said.

Dr. De Ferrari agreed with the opinion voiced by Dr. Chow: The way to prove that TWA can identify patients who do not need an ICD is to randomize patients with a normal TWA result to either receive an ICD or not and then compare the outcomes of patients in these two groups.

'Patients with a normal TWA test have a very good prognosis and are unlikely to benefit from ICD therapy.' DR. DE FERRARI

NEW ORLEANS — New results further supported T-wave alternans as a way to identify patients with nonischemic cardiomyopathy who do not need an implantable cardioverter defibrillator.

Findings from a study with 446 patients done in Italy showed that among patients with nonischemic cardiomyopathy and New York Heart Association class II or III heart failure, “patients with a normal TWA [T-wave alternans] test have a very good prognosis and are unlikely to benefit from ICD [implantable cardioverter defibrillator] therapy,” Dr. Gaetano M. De Ferrari said at the annual meeting of the American College of Cardiology.

In contrast, similar patients with an abnormal TWA result had a fourfold increased risk of cardiac death or a life-threatening ventricular arrhythmia during 18–24 months of follow-up, suggesting that these patients are good candidates for an ICD, said Dr. De Ferrari, chief of the cardiac ICU at Hospital San Matteo in Pavia, Italy.

The results from this “methodologically sound, prospective study confirm with high quality what [results from] other studies have shown,” that the predictive value of TWA in patients with nonischemic cardiomyopathy is similar to its predictive value in patients with ischemic cardiomyopathy, said Dr. Theodore Chow, director of electrophysiology research at the Ohio Heart and Vascular Center in Cincinnati. The new findings, in combination with prior results from other studies, “provide a rationale for a careful, prospective evaluation of whether ICD implants are useful in nonischemic patients with normal TWA.”

Until such a trial is done, “I think that most cardiologists will still generally favor placing ICDs based on data from” the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which showed that ICDs significantly cut mortality in all patients with a left ventricular ejection fraction of 35% or less, said Dr. Chow in an interview.

“We need strategies to sort out who gets an ICD. It's not clear why the use of ICDs is so low, but it's hard to picture that it will be solved by having TWA measurement in all patients,” commented Dr. Mariell L. Jessup, professor of medicine and medical director of heart failure and cardiac transplantation at the University of Pennsylvania, Philadelphia.

The T-Wave Alternans in Patients with Heart Failure (ALPHA) study was done at nine centers in Italy, and was funded in part by Boston Scientific, a company that markets an ICD but does not market equipment used for assessing TWA. The equipment used to measure TWA in the ALPHA study was made by Cambridge Heart.

Dr. De Ferrari and his associates screened more than 3,500 patients with heart failure to identify 446 with nonischemic, dilated cardiomyopathy, a left ventricular ejection fraction of 40% or less, New York Heart Association class II or III heart failure, and no other indication for receiving an ICD. TWA testing identified 154 patients with normal readings and 292 patients with an abnormal result.

During follow-up, the incidence of the study's primary end point—cardiac death or development of a life-threatening ventricular arrhythmia—was 10% in the patients with an abnormal TWA and 3% in those with a normal TWA, a statistically significant difference. When adjusted for baseline differences in age, gender, New York Heart Association class, and left ventricular ejection fraction, patients with an abnormal TWA reading at baseline were 3.2-fold more likely to develop the primary end point than were those with a normal TWA result.

“The most important finding” was the negative predictive value of a normal TWA result at baseline, said Dr. De Ferrari. During 18 months of follow-up, 97% of patients with a normal TWA result were free from the primary end point. “Patients with a normal TWA had a very good prognosis and were unlikely to benefit from an ICD,” he said.

Dr. De Ferrari agreed with the opinion voiced by Dr. Chow: The way to prove that TWA can identify patients who do not need an ICD is to randomize patients with a normal TWA result to either receive an ICD or not and then compare the outcomes of patients in these two groups.

'Patients with a normal TWA test have a very good prognosis and are unlikely to benefit from ICD therapy.' DR. DE FERRARI

NEW ORLEANS — New results further supported T-wave alternans as a way to identify patients with nonischemic cardiomyopathy who do not need an implantable cardioverter defibrillator.

Findings from a study with 446 patients done in Italy showed that among patients with nonischemic cardiomyopathy and New York Heart Association class II or III heart failure, “patients with a normal TWA [T-wave alternans] test have a very good prognosis and are unlikely to benefit from ICD [implantable cardioverter defibrillator] therapy,” Dr. Gaetano M. De Ferrari said at the annual meeting of the American College of Cardiology.

In contrast, similar patients with an abnormal TWA result had a fourfold increased risk of cardiac death or a life-threatening ventricular arrhythmia during 18–24 months of follow-up, suggesting that these patients are good candidates for an ICD, said Dr. De Ferrari, chief of the cardiac ICU at Hospital San Matteo in Pavia, Italy.

The results from this “methodologically sound, prospective study confirm with high quality what [results from] other studies have shown,” that the predictive value of TWA in patients with nonischemic cardiomyopathy is similar to its predictive value in patients with ischemic cardiomyopathy, said Dr. Theodore Chow, director of electrophysiology research at the Ohio Heart and Vascular Center in Cincinnati. The new findings, in combination with prior results from other studies, “provide a rationale for a careful, prospective evaluation of whether ICD implants are useful in nonischemic patients with normal TWA.”

Until such a trial is done, “I think that most cardiologists will still generally favor placing ICDs based on data from” the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which showed that ICDs significantly cut mortality in all patients with a left ventricular ejection fraction of 35% or less, said Dr. Chow in an interview.

“We need strategies to sort out who gets an ICD. It's not clear why the use of ICDs is so low, but it's hard to picture that it will be solved by having TWA measurement in all patients,” commented Dr. Mariell L. Jessup, professor of medicine and medical director of heart failure and cardiac transplantation at the University of Pennsylvania, Philadelphia.

The T-Wave Alternans in Patients with Heart Failure (ALPHA) study was done at nine centers in Italy, and was funded in part by Boston Scientific, a company that markets an ICD but does not market equipment used for assessing TWA. The equipment used to measure TWA in the ALPHA study was made by Cambridge Heart.

Dr. De Ferrari and his associates screened more than 3,500 patients with heart failure to identify 446 with nonischemic, dilated cardiomyopathy, a left ventricular ejection fraction of 40% or less, New York Heart Association class II or III heart failure, and no other indication for receiving an ICD. TWA testing identified 154 patients with normal readings and 292 patients with an abnormal result.

During follow-up, the incidence of the study's primary end point—cardiac death or development of a life-threatening ventricular arrhythmia—was 10% in the patients with an abnormal TWA and 3% in those with a normal TWA, a statistically significant difference. When adjusted for baseline differences in age, gender, New York Heart Association class, and left ventricular ejection fraction, patients with an abnormal TWA reading at baseline were 3.2-fold more likely to develop the primary end point than were those with a normal TWA result.

“The most important finding” was the negative predictive value of a normal TWA result at baseline, said Dr. De Ferrari. During 18 months of follow-up, 97% of patients with a normal TWA result were free from the primary end point. “Patients with a normal TWA had a very good prognosis and were unlikely to benefit from an ICD,” he said.

Dr. De Ferrari agreed with the opinion voiced by Dr. Chow: The way to prove that TWA can identify patients who do not need an ICD is to randomize patients with a normal TWA result to either receive an ICD or not and then compare the outcomes of patients in these two groups.

'Patients with a normal TWA test have a very good prognosis and are unlikely to benefit from ICD therapy.' DR. DE FERRARI

SEATTLE — One-fourth of 182 women with peripartum cardiomyopathy developed major adverse events, half of which were death or heart transplantation, Dr. Sorel Goland reported in a poster presentation at the annual meeting of the Heart Failure Society of America.

Women with peripartum cardiomyopathy who had very low ejection fractions of 25% or who were not white were most likely to develop major adverse events, 50% of which occurred before the diagnosis of peripartum cardiomyopathy was made, said Dr. Goland of the department of cardiology at Cedars-Sinai Medical Center, Los Angeles, and associates. A diagnostic delay of a week or more raised the risk for death or heart transplant fivefold.

“Early diagnosis and aggressive therapy, including treatment of heart failure, anticoagulation, and sudden death prevention, should improve the outcome of patients,” the investigators stated.

The clinical profile of peripartum cardiomyopathy and risk factors for complications have not been well characterized due to its low incidence. Peripartum cardiomyopathy occurs during pregnancy or the postpartum period for unknown reasons and can cause severe complications.

The retrospective review of 182 patients found that 25% died, had a heart transplantation, developed cardiopulmonary arrest, required temporary circulatory support by an intra-aortic balloon pump or a left ventricular assist device, developed pulmonary edema or thromboembolic complications, or received a pacemaker or implantable cardioverter defibrillator. Of the 46 major adverse events, 36 (78%) occurred within 6 months of the diagnosis of peripartum cardiomyopathy.

Of the 182 patients, 24 (13%) died or underwent heart transplantation; 16 of the 24 deaths or transplants happened within 6 months of diagnosis.

Patients with ejection fractions of 25% or less had quadruple the risk for major adverse events in general and for death or heart transplant, compared with patients with higher ejection fractions. Nonwhites were three times as likely to develop major complications and four times likely to die or need a heart transplant, compared with whites.

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SEATTLE — One-fourth of 182 women with peripartum cardiomyopathy developed major adverse events, half of which were death or heart transplantation, Dr. Sorel Goland reported in a poster presentation at the annual meeting of the Heart Failure Society of America.

Women with peripartum cardiomyopathy who had very low ejection fractions of 25% or who were not white were most likely to develop major adverse events, 50% of which occurred before the diagnosis of peripartum cardiomyopathy was made, said Dr. Goland of the department of cardiology at Cedars-Sinai Medical Center, Los Angeles, and associates. A diagnostic delay of a week or more raised the risk for death or heart transplant fivefold.

“Early diagnosis and aggressive therapy, including treatment of heart failure, anticoagulation, and sudden death prevention, should improve the outcome of patients,” the investigators stated.

The clinical profile of peripartum cardiomyopathy and risk factors for complications have not been well characterized due to its low incidence. Peripartum cardiomyopathy occurs during pregnancy or the postpartum period for unknown reasons and can cause severe complications.

The retrospective review of 182 patients found that 25% died, had a heart transplantation, developed cardiopulmonary arrest, required temporary circulatory support by an intra-aortic balloon pump or a left ventricular assist device, developed pulmonary edema or thromboembolic complications, or received a pacemaker or implantable cardioverter defibrillator. Of the 46 major adverse events, 36 (78%) occurred within 6 months of the diagnosis of peripartum cardiomyopathy.

Of the 182 patients, 24 (13%) died or underwent heart transplantation; 16 of the 24 deaths or transplants happened within 6 months of diagnosis.

Patients with ejection fractions of 25% or less had quadruple the risk for major adverse events in general and for death or heart transplant, compared with patients with higher ejection fractions. Nonwhites were three times as likely to develop major complications and four times likely to die or need a heart transplant, compared with whites.

ELSEVIER GLOBAL MEDICAL NEWS

SEATTLE — One-fourth of 182 women with peripartum cardiomyopathy developed major adverse events, half of which were death or heart transplantation, Dr. Sorel Goland reported in a poster presentation at the annual meeting of the Heart Failure Society of America.

Women with peripartum cardiomyopathy who had very low ejection fractions of 25% or who were not white were most likely to develop major adverse events, 50% of which occurred before the diagnosis of peripartum cardiomyopathy was made, said Dr. Goland of the department of cardiology at Cedars-Sinai Medical Center, Los Angeles, and associates. A diagnostic delay of a week or more raised the risk for death or heart transplant fivefold.

“Early diagnosis and aggressive therapy, including treatment of heart failure, anticoagulation, and sudden death prevention, should improve the outcome of patients,” the investigators stated.

The clinical profile of peripartum cardiomyopathy and risk factors for complications have not been well characterized due to its low incidence. Peripartum cardiomyopathy occurs during pregnancy or the postpartum period for unknown reasons and can cause severe complications.

The retrospective review of 182 patients found that 25% died, had a heart transplantation, developed cardiopulmonary arrest, required temporary circulatory support by an intra-aortic balloon pump or a left ventricular assist device, developed pulmonary edema or thromboembolic complications, or received a pacemaker or implantable cardioverter defibrillator. Of the 46 major adverse events, 36 (78%) occurred within 6 months of the diagnosis of peripartum cardiomyopathy.

Of the 182 patients, 24 (13%) died or underwent heart transplantation; 16 of the 24 deaths or transplants happened within 6 months of diagnosis.

Patients with ejection fractions of 25% or less had quadruple the risk for major adverse events in general and for death or heart transplant, compared with patients with higher ejection fractions. Nonwhites were three times as likely to develop major complications and four times likely to die or need a heart transplant, compared with whites.

ELSEVIER GLOBAL MEDICAL NEWS