Doug Brunk

SAN DIEGO – Patients with chronic systolic heart failure who were enrolled in a 12-week tai chi program experienced significant improvements in quality of life, mood, and exercise self-efficacy, compared with patients who were enrolled in an education-only control group, results from a single center study showed.

“Exercise is a recognized important part of heart failure management,” Dr. Gloria Yeh said at the annual meeting of the Heart Failure Society of America. “The focus of prior studies has been on aerobic training, with some new and recent emphasis on strength training. Little, however, is known about the potential value of integrative mind-body movement therapies in this population.”

Tai chi is well suited for heart failure patients, she said, because the physical component “is low impact [and] nonstrenuous, and can easily be performed by the elderly or the more severely deconditioned patients, which may be important in enhancing exercise compliance and self-efficacy.” Reported cardiorespiratory benefits include an increase in peak oxygen uptake and ventilatory capacity, a decrease in blood pressure, and modulations of autonomic tone.

For the current study, Dr. Yeh and her associates at Beth Israel randomized 100 patients with systolic heart failure either to 12 weeks of tai chi classes that met twice weekly or to 12 weeks of an education class that met twice weekly. Testing at baseline, 6 weeks, and 12 weeks in both groups included questionnaires, functional tests, and cardiopulmonary exercise testing.

To be eligible for the trial, patients had to have a left ventricular ejection fraction of 40% or less, be on a stable medical regimen, and have New York Heart Association class I-III heart failure. Study exclusions included unstable angina, MI, cardiac surgery, or cardiac resynchronization therapy in the past 3 months, a history of cardiac arrest in the past 6 months, and unstable ventricular arrhythmia.

The primary outcome measures were quality of life based on the Minnesota Living With Heart Failure Questionnaire (MLHFQ) and exercise capacity based on the 6-minute walk test and peak oxygen consumption (VO2max). Secondary outcome measures included mood based on the Profile of Mood States (POMS), exercise, self-efficacy based on the Cardiac Exercise Self-Efficacy Instrument (CESEI), and serum B-type natriuretic peptide (BNP).

The tai chi class included five basic movements and warm-up exercises that emphasized relaxation, breathing, mind-body awareness, cardiovascular endurance, and a 45-minute videotape for home practice. The mean age of patients in this group was 68 years, and 56% were male.

The education class was led by a nurse practitioner and was based on published Heart Failure Society of America education modules that covered standard heart failure topics such as diet, activity, medications, heart arrhythmia problems, and advance care directives. The mean age of patients in this group was 67 years, and 72% were male.

Dr. Yeh reported that over the course of the 12-week study, 75% of participants in the tai chi group attended all classes, compared with 67% of participants in the education group. Tai chi group participants reported a mean of 10 hours of home practice over the study period.

At 12 weeks, patients in the tai chi group significantly improved their median MLHFQ scores by 19 points (from 28 at baseline to 9 at week 12), but there was no significant change in scores among those in the education group (21 points at baseline and 22 at 12 weeks). “This was quite a striking effect,” Dr. Yeh said.

For the 6-minute walk, patients in the tai chi improved their walk distance by 35 m (from 391 m at baseline to 426 m), a nonsignificant improvement, whereas patients in the education group improved their walk distance by just 2 m (from 392 m to 394 m).

Similarly, there was no significant difference in peak oxygen uptake between the two groups. In the education group, the VO2max dropped from 13.5 mL/kg per minute at baseline to 13 mL/kg per minute at week 12. In the tai chi group, the VO2max rose from 11.9 at baseline to 13 at week 12.

The researchers observed clinically and statistically significant improvements in the tai chi group, compared with the education group, in the POMS total mood disturbance score and in the CESEI score over the 12 weeks. However, there were no differences in serum BNP between the two groups over the course of the study.

“There may be several potential mechanisms for tai chi’s effect,” Dr. Yeh noted. “Observed effects may be due to the intervention’s physical activity and associated training effect. Tai chi includes mild to moderate aerobic exercise as well as upper and lower extremity and core strength training. Some benefits may be due to relaxation and stress reduction components of tai chi acting on stress-related neuromodulators. Similarly, mediation and mind-body integration may favorably affect autonomic tone, and breathing retraining may decrease perceived dyspnea.”

Dr. Yeh acknowledged certain limitations of the study, including its modest sample size, the potential for selection bias, and the fact that participants were not blinded to the intervention group. “We were also unable to isolate benefits to either physical activity or meditative components, or to a combination of both,” she said.

The study was funded by the National Center for Complementary and Alternative Medicine. Dr. Yeh said that she had no relevant financial disclosures to report.

Video interview with Dr. Yeh.

SAN DIEGO – Patients with chronic systolic heart failure who were enrolled in a 12-week tai chi program experienced significant improvements in quality of life, mood, and exercise self-efficacy, compared with patients who were enrolled in an education-only control group, results from a single center study showed.

“Exercise is a recognized important part of heart failure management,” Dr. Gloria Yeh said at the annual meeting of the Heart Failure Society of America. “The focus of prior studies has been on aerobic training, with some new and recent emphasis on strength training. Little, however, is known about the potential value of integrative mind-body movement therapies in this population.”

Tai chi is well suited for heart failure patients, she said, because the physical component “is low impact [and] nonstrenuous, and can easily be performed by the elderly or the more severely deconditioned patients, which may be important in enhancing exercise compliance and self-efficacy.” Reported cardiorespiratory benefits include an increase in peak oxygen uptake and ventilatory capacity, a decrease in blood pressure, and modulations of autonomic tone.

For the current study, Dr. Yeh and her associates at Beth Israel randomized 100 patients with systolic heart failure either to 12 weeks of tai chi classes that met twice weekly or to 12 weeks of an education class that met twice weekly. Testing at baseline, 6 weeks, and 12 weeks in both groups included questionnaires, functional tests, and cardiopulmonary exercise testing.

To be eligible for the trial, patients had to have a left ventricular ejection fraction of 40% or less, be on a stable medical regimen, and have New York Heart Association class I-III heart failure. Study exclusions included unstable angina, MI, cardiac surgery, or cardiac resynchronization therapy in the past 3 months, a history of cardiac arrest in the past 6 months, and unstable ventricular arrhythmia.

The primary outcome measures were quality of life based on the Minnesota Living With Heart Failure Questionnaire (MLHFQ) and exercise capacity based on the 6-minute walk test and peak oxygen consumption (VO2max). Secondary outcome measures included mood based on the Profile of Mood States (POMS), exercise, self-efficacy based on the Cardiac Exercise Self-Efficacy Instrument (CESEI), and serum B-type natriuretic peptide (BNP).

The tai chi class included five basic movements and warm-up exercises that emphasized relaxation, breathing, mind-body awareness, cardiovascular endurance, and a 45-minute videotape for home practice. The mean age of patients in this group was 68 years, and 56% were male.

The education class was led by a nurse practitioner and was based on published Heart Failure Society of America education modules that covered standard heart failure topics such as diet, activity, medications, heart arrhythmia problems, and advance care directives. The mean age of patients in this group was 67 years, and 72% were male.

Dr. Yeh reported that over the course of the 12-week study, 75% of participants in the tai chi group attended all classes, compared with 67% of participants in the education group. Tai chi group participants reported a mean of 10 hours of home practice over the study period.

At 12 weeks, patients in the tai chi group significantly improved their median MLHFQ scores by 19 points (from 28 at baseline to 9 at week 12), but there was no significant change in scores among those in the education group (21 points at baseline and 22 at 12 weeks). “This was quite a striking effect,” Dr. Yeh said.

For the 6-minute walk, patients in the tai chi improved their walk distance by 35 m (from 391 m at baseline to 426 m), a nonsignificant improvement, whereas patients in the education group improved their walk distance by just 2 m (from 392 m to 394 m).

Similarly, there was no significant difference in peak oxygen uptake between the two groups. In the education group, the VO2max dropped from 13.5 mL/kg per minute at baseline to 13 mL/kg per minute at week 12. In the tai chi group, the VO2max rose from 11.9 at baseline to 13 at week 12.

The researchers observed clinically and statistically significant improvements in the tai chi group, compared with the education group, in the POMS total mood disturbance score and in the CESEI score over the 12 weeks. However, there were no differences in serum BNP between the two groups over the course of the study.

“There may be several potential mechanisms for tai chi’s effect,” Dr. Yeh noted. “Observed effects may be due to the intervention’s physical activity and associated training effect. Tai chi includes mild to moderate aerobic exercise as well as upper and lower extremity and core strength training. Some benefits may be due to relaxation and stress reduction components of tai chi acting on stress-related neuromodulators. Similarly, mediation and mind-body integration may favorably affect autonomic tone, and breathing retraining may decrease perceived dyspnea.”

Dr. Yeh acknowledged certain limitations of the study, including its modest sample size, the potential for selection bias, and the fact that participants were not blinded to the intervention group. “We were also unable to isolate benefits to either physical activity or meditative components, or to a combination of both,” she said.

The study was funded by the National Center for Complementary and Alternative Medicine. Dr. Yeh said that she had no relevant financial disclosures to report.

Video interview with Dr. Yeh.

SAN DIEGO – Patients with chronic systolic heart failure who were enrolled in a 12-week tai chi program experienced significant improvements in quality of life, mood, and exercise self-efficacy, compared with patients who were enrolled in an education-only control group, results from a single center study showed.

“Exercise is a recognized important part of heart failure management,” Dr. Gloria Yeh said at the annual meeting of the Heart Failure Society of America. “The focus of prior studies has been on aerobic training, with some new and recent emphasis on strength training. Little, however, is known about the potential value of integrative mind-body movement therapies in this population.”

Tai chi is well suited for heart failure patients, she said, because the physical component “is low impact [and] nonstrenuous, and can easily be performed by the elderly or the more severely deconditioned patients, which may be important in enhancing exercise compliance and self-efficacy.” Reported cardiorespiratory benefits include an increase in peak oxygen uptake and ventilatory capacity, a decrease in blood pressure, and modulations of autonomic tone.

For the current study, Dr. Yeh and her associates at Beth Israel randomized 100 patients with systolic heart failure either to 12 weeks of tai chi classes that met twice weekly or to 12 weeks of an education class that met twice weekly. Testing at baseline, 6 weeks, and 12 weeks in both groups included questionnaires, functional tests, and cardiopulmonary exercise testing.

To be eligible for the trial, patients had to have a left ventricular ejection fraction of 40% or less, be on a stable medical regimen, and have New York Heart Association class I-III heart failure. Study exclusions included unstable angina, MI, cardiac surgery, or cardiac resynchronization therapy in the past 3 months, a history of cardiac arrest in the past 6 months, and unstable ventricular arrhythmia.

The primary outcome measures were quality of life based on the Minnesota Living With Heart Failure Questionnaire (MLHFQ) and exercise capacity based on the 6-minute walk test and peak oxygen consumption (VO2max). Secondary outcome measures included mood based on the Profile of Mood States (POMS), exercise, self-efficacy based on the Cardiac Exercise Self-Efficacy Instrument (CESEI), and serum B-type natriuretic peptide (BNP).

The tai chi class included five basic movements and warm-up exercises that emphasized relaxation, breathing, mind-body awareness, cardiovascular endurance, and a 45-minute videotape for home practice. The mean age of patients in this group was 68 years, and 56% were male.

The education class was led by a nurse practitioner and was based on published Heart Failure Society of America education modules that covered standard heart failure topics such as diet, activity, medications, heart arrhythmia problems, and advance care directives. The mean age of patients in this group was 67 years, and 72% were male.

Dr. Yeh reported that over the course of the 12-week study, 75% of participants in the tai chi group attended all classes, compared with 67% of participants in the education group. Tai chi group participants reported a mean of 10 hours of home practice over the study period.

At 12 weeks, patients in the tai chi group significantly improved their median MLHFQ scores by 19 points (from 28 at baseline to 9 at week 12), but there was no significant change in scores among those in the education group (21 points at baseline and 22 at 12 weeks). “This was quite a striking effect,” Dr. Yeh said.

For the 6-minute walk, patients in the tai chi improved their walk distance by 35 m (from 391 m at baseline to 426 m), a nonsignificant improvement, whereas patients in the education group improved their walk distance by just 2 m (from 392 m to 394 m).

Similarly, there was no significant difference in peak oxygen uptake between the two groups. In the education group, the VO2max dropped from 13.5 mL/kg per minute at baseline to 13 mL/kg per minute at week 12. In the tai chi group, the VO2max rose from 11.9 at baseline to 13 at week 12.

The researchers observed clinically and statistically significant improvements in the tai chi group, compared with the education group, in the POMS total mood disturbance score and in the CESEI score over the 12 weeks. However, there were no differences in serum BNP between the two groups over the course of the study.

“There may be several potential mechanisms for tai chi’s effect,” Dr. Yeh noted. “Observed effects may be due to the intervention’s physical activity and associated training effect. Tai chi includes mild to moderate aerobic exercise as well as upper and lower extremity and core strength training. Some benefits may be due to relaxation and stress reduction components of tai chi acting on stress-related neuromodulators. Similarly, mediation and mind-body integration may favorably affect autonomic tone, and breathing retraining may decrease perceived dyspnea.”

Dr. Yeh acknowledged certain limitations of the study, including its modest sample size, the potential for selection bias, and the fact that participants were not blinded to the intervention group. “We were also unable to isolate benefits to either physical activity or meditative components, or to a combination of both,” she said.

The study was funded by the National Center for Complementary and Alternative Medicine. Dr. Yeh said that she had no relevant financial disclosures to report.

Video interview with Dr. Yeh.

SANTA BARBARA, Calif. – Sometimes, changes in skin appearance serve as the first marker of inherited internal disease.

At the annual meeting of the California Society of Dermatology and Dermatologic Surgery, Dr. Bruce H. Thiers highlighted common dermatologic signs associated with several of these syndromes:

• Cowden syndrome. This autosomal dominant syndrome is a marker for the eventual development of breast cancer and thyroid tumors. It is characterized by wart-like papules known as trichilemmomas. “They can occur anywhere, especially on the face,” said Dr. Thiers, of the department of dermatology and dermatologic surgery at the Medical University of South Carolina, Charleston. “You can also see other benign lesions like angiomas and lipomas. I’ve had a few patients with Cowden syndrome who have a strong history of breast cancer and who have elected to have prophylactic mastectomies.”

Up to 50% of women with Cowden’s disease get breast cancer, and about 10% are diagnosed with thyroid cancer, he added.

– Gardner syndrome. This condition typically presents as deforming epidermoid cysts, though it may also include fibromas, lipomas, leiomyomas, trichoepitheliomas, and neurofibromas. About one half of patients develop osteomas involving the membranous bones of the face and head. “Many reference sources say that the incidence of colon cancer in Gardner syndrome nears 100%,” said Dr. Thiers. “The standard of care in these patients appears to be frequent colonoscopies with consideration of prophylactic colectomy.”

– Muir-Torre syndrome. This condition is most often associated with carcinoma of the lower gastrointestinal tract, “although the tumors tend to be less aggressive than they are with Gardner syndrome,” Dr. Thiers said. The characteristic lesion is a sebaceous neoplasm, usually located on the trunk. “It could be benign, like a sebaceous adenoma, or it could be a sebaceous carcinoma.”

– Birt-Hogg-Dubé syndrome. This condition is associated with kidney cancer and is marked by benign fibrofolliculomas and trichodiscomas that most often occur on the head and neck. “These patients have an increased incidence of pneumothorax as well,” he said.

– Hereditary leiomyomatosis and renal cell cancer syndrome. This condition is marked by cutaneous leiomyomas and papillary renal cell carcinoma. The skin lesions typically occur before the age of 25. “These patients not only have an increased risk of kidney cancer, but these tumors tend to occur at a very young age, and they tend to be quite aggressive,” Dr. Thiers noted. “If you see a patient with multiple leiomyomas, realize that this might not be purely a cutaneous phenomenon but part of a significant paraneoplastic syndrome.”

Dr. Thiers said that he had no relevant financial conflicts to disclose.

SANTA BARBARA, Calif. – Sometimes, changes in skin appearance serve as the first marker of inherited internal disease.

At the annual meeting of the California Society of Dermatology and Dermatologic Surgery, Dr. Bruce H. Thiers highlighted common dermatologic signs associated with several of these syndromes:

• Cowden syndrome. This autosomal dominant syndrome is a marker for the eventual development of breast cancer and thyroid tumors. It is characterized by wart-like papules known as trichilemmomas. “They can occur anywhere, especially on the face,” said Dr. Thiers, of the department of dermatology and dermatologic surgery at the Medical University of South Carolina, Charleston. “You can also see other benign lesions like angiomas and lipomas. I’ve had a few patients with Cowden syndrome who have a strong history of breast cancer and who have elected to have prophylactic mastectomies.”

Up to 50% of women with Cowden’s disease get breast cancer, and about 10% are diagnosed with thyroid cancer, he added.

– Gardner syndrome. This condition typically presents as deforming epidermoid cysts, though it may also include fibromas, lipomas, leiomyomas, trichoepitheliomas, and neurofibromas. About one half of patients develop osteomas involving the membranous bones of the face and head. “Many reference sources say that the incidence of colon cancer in Gardner syndrome nears 100%,” said Dr. Thiers. “The standard of care in these patients appears to be frequent colonoscopies with consideration of prophylactic colectomy.”

– Muir-Torre syndrome. This condition is most often associated with carcinoma of the lower gastrointestinal tract, “although the tumors tend to be less aggressive than they are with Gardner syndrome,” Dr. Thiers said. The characteristic lesion is a sebaceous neoplasm, usually located on the trunk. “It could be benign, like a sebaceous adenoma, or it could be a sebaceous carcinoma.”

– Birt-Hogg-Dubé syndrome. This condition is associated with kidney cancer and is marked by benign fibrofolliculomas and trichodiscomas that most often occur on the head and neck. “These patients have an increased incidence of pneumothorax as well,” he said.

– Hereditary leiomyomatosis and renal cell cancer syndrome. This condition is marked by cutaneous leiomyomas and papillary renal cell carcinoma. The skin lesions typically occur before the age of 25. “These patients not only have an increased risk of kidney cancer, but these tumors tend to occur at a very young age, and they tend to be quite aggressive,” Dr. Thiers noted. “If you see a patient with multiple leiomyomas, realize that this might not be purely a cutaneous phenomenon but part of a significant paraneoplastic syndrome.”

Dr. Thiers said that he had no relevant financial conflicts to disclose.

SANTA BARBARA, Calif. – Sometimes, changes in skin appearance serve as the first marker of inherited internal disease.

At the annual meeting of the California Society of Dermatology and Dermatologic Surgery, Dr. Bruce H. Thiers highlighted common dermatologic signs associated with several of these syndromes:

• Cowden syndrome. This autosomal dominant syndrome is a marker for the eventual development of breast cancer and thyroid tumors. It is characterized by wart-like papules known as trichilemmomas. “They can occur anywhere, especially on the face,” said Dr. Thiers, of the department of dermatology and dermatologic surgery at the Medical University of South Carolina, Charleston. “You can also see other benign lesions like angiomas and lipomas. I’ve had a few patients with Cowden syndrome who have a strong history of breast cancer and who have elected to have prophylactic mastectomies.”

Up to 50% of women with Cowden’s disease get breast cancer, and about 10% are diagnosed with thyroid cancer, he added.

– Gardner syndrome. This condition typically presents as deforming epidermoid cysts, though it may also include fibromas, lipomas, leiomyomas, trichoepitheliomas, and neurofibromas. About one half of patients develop osteomas involving the membranous bones of the face and head. “Many reference sources say that the incidence of colon cancer in Gardner syndrome nears 100%,” said Dr. Thiers. “The standard of care in these patients appears to be frequent colonoscopies with consideration of prophylactic colectomy.”

– Muir-Torre syndrome. This condition is most often associated with carcinoma of the lower gastrointestinal tract, “although the tumors tend to be less aggressive than they are with Gardner syndrome,” Dr. Thiers said. The characteristic lesion is a sebaceous neoplasm, usually located on the trunk. “It could be benign, like a sebaceous adenoma, or it could be a sebaceous carcinoma.”

– Birt-Hogg-Dubé syndrome. This condition is associated with kidney cancer and is marked by benign fibrofolliculomas and trichodiscomas that most often occur on the head and neck. “These patients have an increased incidence of pneumothorax as well,” he said.

– Hereditary leiomyomatosis and renal cell cancer syndrome. This condition is marked by cutaneous leiomyomas and papillary renal cell carcinoma. The skin lesions typically occur before the age of 25. “These patients not only have an increased risk of kidney cancer, but these tumors tend to occur at a very young age, and they tend to be quite aggressive,” Dr. Thiers noted. “If you see a patient with multiple leiomyomas, realize that this might not be purely a cutaneous phenomenon but part of a significant paraneoplastic syndrome.”

Dr. Thiers said that he had no relevant financial conflicts to disclose.

Overweight or obese women who were assigned to a structured weight-loss program with free prepared meals lost a significantly greater amount of weight at 2 years than did those who received usual care.

In addition, a greater proportion of women enrolled in the program maintained a 5% weight loss at 2 years than did those who received usual care.

“For clinical practitioners, the evidence suggests that the structured program as applied in this study provides another route for their overweight or obese patients to achieve and maintain weight loss through behavioral changes for at least a 2-year period,” researchers led by Cheryl L. Rock, Ph.D., of the University of California, San Diego School of Medicine, wrote in a study published online Oct. 9 in JAMA.

For the study, 442 overweight or obese women at one of four study sites were randomly assigned to one of three groups: an in-person center-based intervention group, a telephone-based intervention group, or a usual care group.

Women in the intervention groups received free one-on-one weight-loss counseling for 2 years, and were educated on recommendations for a nutritionally sound, reduced-calorie diet with 20-30% of calories from fat, and 30 minutes of physical exercise at least 5 days per week (JAMA 2010 Oct. 9 [Epub doi:10.1001/jama.2010.1503]). They also received free access to prepackaged prepared foods from Jenny Craig Inc. to help them achieve their nutritional goals.

“Over time, participants were transitioned to a meal plan based mainly not on food provided from the commercial program, although participants could choose to include one prepackaged meal per day during weight-loss maintenance,” Dr. Rock and her associates noted.

Women assigned to the usual care group received a 1-hour consultation with a dietetics professional at baseline and at 6 months. During these sessions, they received publicly available materials on dietary and physical activity recommendations to achieve and maintain weight loss, as well as sample meal plans and advice on reading food labels and estimating serving sizes. Women in this group were followed up monthly via e-mail or telephone contact.

All study participants received $25 for each completed clinic visit, but no payment was provided for participating in the intervention or counseling sessions.

The mean age of study participants was 44 years, and 73% were non-Hispanic white. At 2 years, 407 participants remained in the trial, for a retention rate of 92%. The mean weight loss was 7.4 kg in the center-based group, 6.2 kg in the telephone-based group, and 2.0 kg in the usual care group. In addition, 62% in the center-based group and 56% in the telephone-based group had maintained a weight loss of at least 5% by the end of the study period, compared with just 29% in the usual care group.

A reduction in C-reactive protein levels and improvement in leptin levels were greater in both intervention groups compared with the usual care group, but there were no significant intervention effects on other measures, including cardiopulmonary fitness, cholesterol levels, physical or mental quality of life, or depression.

Dr. Rock and her associates acknowledged certain limitations of the study, including the fact that the prepackaged foods were provided free of charge. If women in the intervention groups were paying out-of-pocket, participant food costs would have averaged $85 per week for a total of $4,080 for the year, they wrote. “For the second year of the program, when participants transitioned to their own foods, food costs would have averaged $45 per week for a total of $2,160 for the year.”

They also noted that weight-loss program counselors were unblinded, “which may have influenced their behavior and effectiveness, although they were instructed to provide the program and services as designed to be delivered to paying customers.”

The study was supported by Jenny Craig Inc., which had a minimal role in the design of the study. Dr. Rock disclosed that she served on the advisory board of Jenny Craig from 2003 to 2004. None of her coauthors reported having any relevant financial conflicts.

Overweight or obese women who were assigned to a structured weight-loss program with free prepared meals lost a significantly greater amount of weight at 2 years than did those who received usual care.

In addition, a greater proportion of women enrolled in the program maintained a 5% weight loss at 2 years than did those who received usual care.

“For clinical practitioners, the evidence suggests that the structured program as applied in this study provides another route for their overweight or obese patients to achieve and maintain weight loss through behavioral changes for at least a 2-year period,” researchers led by Cheryl L. Rock, Ph.D., of the University of California, San Diego School of Medicine, wrote in a study published online Oct. 9 in JAMA.

For the study, 442 overweight or obese women at one of four study sites were randomly assigned to one of three groups: an in-person center-based intervention group, a telephone-based intervention group, or a usual care group.

Women in the intervention groups received free one-on-one weight-loss counseling for 2 years, and were educated on recommendations for a nutritionally sound, reduced-calorie diet with 20-30% of calories from fat, and 30 minutes of physical exercise at least 5 days per week (JAMA 2010 Oct. 9 [Epub doi:10.1001/jama.2010.1503]). They also received free access to prepackaged prepared foods from Jenny Craig Inc. to help them achieve their nutritional goals.

“Over time, participants were transitioned to a meal plan based mainly not on food provided from the commercial program, although participants could choose to include one prepackaged meal per day during weight-loss maintenance,” Dr. Rock and her associates noted.

Women assigned to the usual care group received a 1-hour consultation with a dietetics professional at baseline and at 6 months. During these sessions, they received publicly available materials on dietary and physical activity recommendations to achieve and maintain weight loss, as well as sample meal plans and advice on reading food labels and estimating serving sizes. Women in this group were followed up monthly via e-mail or telephone contact.

All study participants received $25 for each completed clinic visit, but no payment was provided for participating in the intervention or counseling sessions.

The mean age of study participants was 44 years, and 73% were non-Hispanic white. At 2 years, 407 participants remained in the trial, for a retention rate of 92%. The mean weight loss was 7.4 kg in the center-based group, 6.2 kg in the telephone-based group, and 2.0 kg in the usual care group. In addition, 62% in the center-based group and 56% in the telephone-based group had maintained a weight loss of at least 5% by the end of the study period, compared with just 29% in the usual care group.

A reduction in C-reactive protein levels and improvement in leptin levels were greater in both intervention groups compared with the usual care group, but there were no significant intervention effects on other measures, including cardiopulmonary fitness, cholesterol levels, physical or mental quality of life, or depression.

Dr. Rock and her associates acknowledged certain limitations of the study, including the fact that the prepackaged foods were provided free of charge. If women in the intervention groups were paying out-of-pocket, participant food costs would have averaged $85 per week for a total of $4,080 for the year, they wrote. “For the second year of the program, when participants transitioned to their own foods, food costs would have averaged $45 per week for a total of $2,160 for the year.”

They also noted that weight-loss program counselors were unblinded, “which may have influenced their behavior and effectiveness, although they were instructed to provide the program and services as designed to be delivered to paying customers.”

The study was supported by Jenny Craig Inc., which had a minimal role in the design of the study. Dr. Rock disclosed that she served on the advisory board of Jenny Craig from 2003 to 2004. None of her coauthors reported having any relevant financial conflicts.

Overweight or obese women who were assigned to a structured weight-loss program with free prepared meals lost a significantly greater amount of weight at 2 years than did those who received usual care.

In addition, a greater proportion of women enrolled in the program maintained a 5% weight loss at 2 years than did those who received usual care.

“For clinical practitioners, the evidence suggests that the structured program as applied in this study provides another route for their overweight or obese patients to achieve and maintain weight loss through behavioral changes for at least a 2-year period,” researchers led by Cheryl L. Rock, Ph.D., of the University of California, San Diego School of Medicine, wrote in a study published online Oct. 9 in JAMA.

For the study, 442 overweight or obese women at one of four study sites were randomly assigned to one of three groups: an in-person center-based intervention group, a telephone-based intervention group, or a usual care group.

Women in the intervention groups received free one-on-one weight-loss counseling for 2 years, and were educated on recommendations for a nutritionally sound, reduced-calorie diet with 20-30% of calories from fat, and 30 minutes of physical exercise at least 5 days per week (JAMA 2010 Oct. 9 [Epub doi:10.1001/jama.2010.1503]). They also received free access to prepackaged prepared foods from Jenny Craig Inc. to help them achieve their nutritional goals.

“Over time, participants were transitioned to a meal plan based mainly not on food provided from the commercial program, although participants could choose to include one prepackaged meal per day during weight-loss maintenance,” Dr. Rock and her associates noted.

Women assigned to the usual care group received a 1-hour consultation with a dietetics professional at baseline and at 6 months. During these sessions, they received publicly available materials on dietary and physical activity recommendations to achieve and maintain weight loss, as well as sample meal plans and advice on reading food labels and estimating serving sizes. Women in this group were followed up monthly via e-mail or telephone contact.

All study participants received $25 for each completed clinic visit, but no payment was provided for participating in the intervention or counseling sessions.

The mean age of study participants was 44 years, and 73% were non-Hispanic white. At 2 years, 407 participants remained in the trial, for a retention rate of 92%. The mean weight loss was 7.4 kg in the center-based group, 6.2 kg in the telephone-based group, and 2.0 kg in the usual care group. In addition, 62% in the center-based group and 56% in the telephone-based group had maintained a weight loss of at least 5% by the end of the study period, compared with just 29% in the usual care group.

A reduction in C-reactive protein levels and improvement in leptin levels were greater in both intervention groups compared with the usual care group, but there were no significant intervention effects on other measures, including cardiopulmonary fitness, cholesterol levels, physical or mental quality of life, or depression.

Dr. Rock and her associates acknowledged certain limitations of the study, including the fact that the prepackaged foods were provided free of charge. If women in the intervention groups were paying out-of-pocket, participant food costs would have averaged $85 per week for a total of $4,080 for the year, they wrote. “For the second year of the program, when participants transitioned to their own foods, food costs would have averaged $45 per week for a total of $2,160 for the year.”

They also noted that weight-loss program counselors were unblinded, “which may have influenced their behavior and effectiveness, although they were instructed to provide the program and services as designed to be delivered to paying customers.”

The study was supported by Jenny Craig Inc., which had a minimal role in the design of the study. Dr. Rock disclosed that she served on the advisory board of Jenny Craig from 2003 to 2004. None of her coauthors reported having any relevant financial conflicts.

Overweight or obese women who were assigned to a structured weight-loss program with free prepared meals lost a significantly greater amount of weight at 2 years than did those who received usual care.

In addition, a greater proportion of women enrolled in the program maintained a 5% weight loss at 2 years than did those who received usual care.

“For clinical practitioners, the evidence suggests that the structured program as applied in this study provides another route for their overweight or obese patients to achieve and maintain weight loss through behavioral changes for at least a 2-year period,” researchers led by Cheryl L. Rock, Ph.D., of the University of California, San Diego School of Medicine, wrote in a study published online Oct. 9 in JAMA.

For the study, 442 overweight or obese women at one of four study sites were randomly assigned to one of three groups: an in-person center-based intervention group, a telephone-based intervention group, or a usual care group.

Women in the intervention groups received free one-on-one weight-loss counseling for 2 years, and were educated on recommendations for a nutritionally sound, reduced-calorie diet with 20-30% of calories from fat, and 30 minutes of physical exercise at least 5 days per week (JAMA 2010 Oct. 9 [Epub doi:10.1001/jama.2010.1503]). They also received free access to prepackaged prepared foods from Jenny Craig Inc. to help them achieve their nutritional goals.

“Over time, participants were transitioned to a meal plan based mainly not on food provided from the commercial program, although participants could choose to include one prepackaged meal per day during weight-loss maintenance,” Dr. Rock and her associates noted.

Women assigned to the usual care group received a 1-hour consultation with a dietetics professional at baseline and at 6 months. During these sessions, they received publicly available materials on dietary and physical activity recommendations to achieve and maintain weight loss, as well as sample meal plans and advice on reading food labels and estimating serving sizes. Women in this group were followed up monthly via e-mail or telephone contact.

All study participants received $25 for each completed clinic visit, but no payment was provided for participating in the intervention or counseling sessions.

The mean age of study participants was 44 years, and 73% were non-Hispanic white. At 2 years, 407 participants remained in the trial, for a retention rate of 92%. The mean weight loss was 7.4 kg in the center-based group, 6.2 kg in the telephone-based group, and 2.0 kg in the usual care group. In addition, 62% in the center-based group and 56% in the telephone-based group had maintained a weight loss of at least 5% by the end of the study period, compared with just 29% in the usual care group.

A reduction in C-reactive protein levels and improvement in leptin levels were greater in both intervention groups compared with the usual care group, but there were no significant intervention effects on other measures, including cardiopulmonary fitness, cholesterol levels, physical or mental quality of life, or depression.

Dr. Rock and her associates acknowledged certain limitations of the study, including the fact that the prepackaged foods were provided free of charge. If women in the intervention groups were paying out-of-pocket, participant food costs would have averaged $85 per week for a total of $4,080 for the year, they wrote. “For the second year of the program, when participants transitioned to their own foods, food costs would have averaged $45 per week for a total of $2,160 for the year.”

They also noted that weight-loss program counselors were unblinded, “which may have influenced their behavior and effectiveness, although they were instructed to provide the program and services as designed to be delivered to paying customers.”

In an accompanying editorial, Rena R. Wing, Ph.D., wrote, “The findings of this trial raise the possibility that if structured commercial weight-loss programs could be provided free-of-charge to participants, both retention and average weight-loss outcomes might be far better than when participants must pay for these programs. Currently, insurance companies will cover the cost of bariatric surgery for obesity (estimated at $19,000-$29,000 per patient from insurance data), but they do not cover the cost of commercial weight-loss programs (such as that evaluated in this study, with estimated costs of approximately $1,600 for 12 weeks of the program and for food).”

Dr. Wing, director of the Weight Control and Diabetes Research Center at Miriam Hospital, Providence, R.I., continued: “Providing commercial weight-loss programs free-of-charge to participants might be a worthwhile health care investment. Future studies should directly compare the outcomes achieved in a variety of different commercial weight-loss programs and examine whether providing these programs free-of-charge to participants would be a cost-effective approach” (JAMA 2010 Oct. 9 [Epub doi:10.1001/jama.2010.1529).

She disclosed that preparation of the editorial was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases.

The study was supported by Jenny Craig Inc., which had a minimal role in the design of the study. Dr. Rock disclosed that she served on the advisory board of Jenny Craig from 2003 to 2004. None of her coauthors reported having any relevant financial conflicts.

Overweight or obese women who were assigned to a structured weight-loss program with free prepared meals lost a significantly greater amount of weight at 2 years than did those who received usual care.

In addition, a greater proportion of women enrolled in the program maintained a 5% weight loss at 2 years than did those who received usual care.

“For clinical practitioners, the evidence suggests that the structured program as applied in this study provides another route for their overweight or obese patients to achieve and maintain weight loss through behavioral changes for at least a 2-year period,” researchers led by Cheryl L. Rock, Ph.D., of the University of California, San Diego School of Medicine, wrote in a study published online Oct. 9 in JAMA.

For the study, 442 overweight or obese women at one of four study sites were randomly assigned to one of three groups: an in-person center-based intervention group, a telephone-based intervention group, or a usual care group.

Women in the intervention groups received free one-on-one weight-loss counseling for 2 years, and were educated on recommendations for a nutritionally sound, reduced-calorie diet with 20-30% of calories from fat, and 30 minutes of physical exercise at least 5 days per week (JAMA 2010 Oct. 9 [Epub doi:10.1001/jama.2010.1503]). They also received free access to prepackaged prepared foods from Jenny Craig Inc. to help them achieve their nutritional goals.

“Over time, participants were transitioned to a meal plan based mainly not on food provided from the commercial program, although participants could choose to include one prepackaged meal per day during weight-loss maintenance,” Dr. Rock and her associates noted.

Women assigned to the usual care group received a 1-hour consultation with a dietetics professional at baseline and at 6 months. During these sessions, they received publicly available materials on dietary and physical activity recommendations to achieve and maintain weight loss, as well as sample meal plans and advice on reading food labels and estimating serving sizes. Women in this group were followed up monthly via e-mail or telephone contact.

All study participants received $25 for each completed clinic visit, but no payment was provided for participating in the intervention or counseling sessions.

The mean age of study participants was 44 years, and 73% were non-Hispanic white. At 2 years, 407 participants remained in the trial, for a retention rate of 92%. The mean weight loss was 7.4 kg in the center-based group, 6.2 kg in the telephone-based group, and 2.0 kg in the usual care group. In addition, 62% in the center-based group and 56% in the telephone-based group had maintained a weight loss of at least 5% by the end of the study period, compared with just 29% in the usual care group.

A reduction in C-reactive protein levels and improvement in leptin levels were greater in both intervention groups compared with the usual care group, but there were no significant intervention effects on other measures, including cardiopulmonary fitness, cholesterol levels, physical or mental quality of life, or depression.

Dr. Rock and her associates acknowledged certain limitations of the study, including the fact that the prepackaged foods were provided free of charge. If women in the intervention groups were paying out-of-pocket, participant food costs would have averaged $85 per week for a total of $4,080 for the year, they wrote. “For the second year of the program, when participants transitioned to their own foods, food costs would have averaged $45 per week for a total of $2,160 for the year.”

They also noted that weight-loss program counselors were unblinded, “which may have influenced their behavior and effectiveness, although they were instructed to provide the program and services as designed to be delivered to paying customers.”

In an accompanying editorial, Rena R. Wing, Ph.D., wrote, “The findings of this trial raise the possibility that if structured commercial weight-loss programs could be provided free-of-charge to participants, both retention and average weight-loss outcomes might be far better than when participants must pay for these programs. Currently, insurance companies will cover the cost of bariatric surgery for obesity (estimated at $19,000-$29,000 per patient from insurance data), but they do not cover the cost of commercial weight-loss programs (such as that evaluated in this study, with estimated costs of approximately $1,600 for 12 weeks of the program and for food).”

Dr. Wing, director of the Weight Control and Diabetes Research Center at Miriam Hospital, Providence, R.I., continued: “Providing commercial weight-loss programs free-of-charge to participants might be a worthwhile health care investment. Future studies should directly compare the outcomes achieved in a variety of different commercial weight-loss programs and examine whether providing these programs free-of-charge to participants would be a cost-effective approach” (JAMA 2010 Oct. 9 [Epub doi:10.1001/jama.2010.1529).

She disclosed that preparation of the editorial was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases.

The study was supported by Jenny Craig Inc., which had a minimal role in the design of the study. Dr. Rock disclosed that she served on the advisory board of Jenny Craig from 2003 to 2004. None of her coauthors reported having any relevant financial conflicts.

Overweight or obese women who were assigned to a structured weight-loss program with free prepared meals lost a significantly greater amount of weight at 2 years than did those who received usual care.

In addition, a greater proportion of women enrolled in the program maintained a 5% weight loss at 2 years than did those who received usual care.

“For clinical practitioners, the evidence suggests that the structured program as applied in this study provides another route for their overweight or obese patients to achieve and maintain weight loss through behavioral changes for at least a 2-year period,” researchers led by Cheryl L. Rock, Ph.D., of the University of California, San Diego School of Medicine, wrote in a study published online Oct. 9 in JAMA.

For the study, 442 overweight or obese women at one of four study sites were randomly assigned to one of three groups: an in-person center-based intervention group, a telephone-based intervention group, or a usual care group.

Women in the intervention groups received free one-on-one weight-loss counseling for 2 years, and were educated on recommendations for a nutritionally sound, reduced-calorie diet with 20-30% of calories from fat, and 30 minutes of physical exercise at least 5 days per week (JAMA 2010 Oct. 9 [Epub doi:10.1001/jama.2010.1503]). They also received free access to prepackaged prepared foods from Jenny Craig Inc. to help them achieve their nutritional goals.

“Over time, participants were transitioned to a meal plan based mainly not on food provided from the commercial program, although participants could choose to include one prepackaged meal per day during weight-loss maintenance,” Dr. Rock and her associates noted.

Women assigned to the usual care group received a 1-hour consultation with a dietetics professional at baseline and at 6 months. During these sessions, they received publicly available materials on dietary and physical activity recommendations to achieve and maintain weight loss, as well as sample meal plans and advice on reading food labels and estimating serving sizes. Women in this group were followed up monthly via e-mail or telephone contact.

All study participants received $25 for each completed clinic visit, but no payment was provided for participating in the intervention or counseling sessions.

The mean age of study participants was 44 years, and 73% were non-Hispanic white. At 2 years, 407 participants remained in the trial, for a retention rate of 92%. The mean weight loss was 7.4 kg in the center-based group, 6.2 kg in the telephone-based group, and 2.0 kg in the usual care group. In addition, 62% in the center-based group and 56% in the telephone-based group had maintained a weight loss of at least 5% by the end of the study period, compared with just 29% in the usual care group.

A reduction in C-reactive protein levels and improvement in leptin levels were greater in both intervention groups compared with the usual care group, but there were no significant intervention effects on other measures, including cardiopulmonary fitness, cholesterol levels, physical or mental quality of life, or depression.

Dr. Rock and her associates acknowledged certain limitations of the study, including the fact that the prepackaged foods were provided free of charge. If women in the intervention groups were paying out-of-pocket, participant food costs would have averaged $85 per week for a total of $4,080 for the year, they wrote. “For the second year of the program, when participants transitioned to their own foods, food costs would have averaged $45 per week for a total of $2,160 for the year.”

They also noted that weight-loss program counselors were unblinded, “which may have influenced their behavior and effectiveness, although they were instructed to provide the program and services as designed to be delivered to paying customers.”

In an accompanying editorial, Rena R. Wing, Ph.D., wrote, “The findings of this trial raise the possibility that if structured commercial weight-loss programs could be provided free-of-charge to participants, both retention and average weight-loss outcomes might be far better than when participants must pay for these programs. Currently, insurance companies will cover the cost of bariatric surgery for obesity (estimated at $19,000-$29,000 per patient from insurance data), but they do not cover the cost of commercial weight-loss programs (such as that evaluated in this study, with estimated costs of approximately $1,600 for 12 weeks of the program and for food).”

Dr. Wing, director of the Weight Control and Diabetes Research Center at Miriam Hospital, Providence, R.I., continued: “Providing commercial weight-loss programs free-of-charge to participants might be a worthwhile health care investment. Future studies should directly compare the outcomes achieved in a variety of different commercial weight-loss programs and examine whether providing these programs free-of-charge to participants would be a cost-effective approach” (JAMA 2010 Oct. 9 [Epub doi:10.1001/jama.2010.1529).

She disclosed that preparation of the editorial was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases.

The study was supported by Jenny Craig Inc., which had a minimal role in the design of the study. Dr. Rock disclosed that she served on the advisory board of Jenny Craig from 2003 to 2004. None of her coauthors reported having any relevant financial conflicts.

SAN DIEGO – Patients with heart failure on optimal medical therapy who received a multidisciplinary, nonpharmacologic intervention for follow-up care and observation had a 38% reduction in death and rehospitalization for heart failure at 1 year, compared with patients who received usual care.

They also experienced significant improvements in depression scores from baseline, compared with their counterparts, Dr. Viacheslav Mareev reported at the annual meeting of the Heart Failure Society of America.

“It’s well known that many patients with congestive heart failure have depression,” said Dr. Mareev of the Russian Society of Heart Failure Specialists, Moscow. A recent meta-analysis of trials studying the association found that the prevalence ranges from 19% to 34%, and that the prevalence of depression worsens as heart failure worsens (J. Am. Coll. Cardiol. 2006;48:1527-37).

For the current trial, known as CHANCE (Congestive Heart Failure: A Multidisciplinary Nonpharmacological Approach for Changing in Rehospitalization and Prognosis), Dr. Mareev and his associates at 38 sites in 24 cities in Russia randomized 385 patients with New York Heart Association class III or IV heart failure to receive optimal medical treatment plus usual care, and 360 patients to receive optimal medical treatment plus education and observation by a multidisciplinary team of clinicians.

Patients in the intervention group attended four 30-minute, in-hospital educational sessions about how to live optimally with heart failure. After discharge, bilateral phone contact was made once weekly during the first month, twice a month until month 6, and then monthly until month 12. To date, none of the patients has been lost to follow-up, Dr. Mareev said.

Both groups of patients completed the HADS (Hospital Anxiety and Depression Scale) at baseline and at 12 months. In this scale, a score of less than 7 suggests the absence of anxiety and/or depression, a score of 7-10 suggests subclinical or minor anxiety and/or depression, and a score greater than 10 suggests clinically relevant, severe anxiety and/or depression.

The mean age of the study participants was 63 years, 60% were male, and 72% had NYHA class III heart failure.

Dr. Mareev reported that patients in the intervention group had a 38% reduction in death and rehospitalization for heart failure, compared with patients in the usual-care group.

Baseline HADS scores in the intervention group fell significantly (from 9.7 at baseline to 7.1 at 1 year), whereas scores in the usual-care group dropped slightly but not significantly (from 9.3 to 8.7). Dr. Mareev said that the number of patients who scored greater than 10 on the HADS dropped slightly between baseline and 1 year for patients in the usual-care group (from 31% to 30%), but dropped markedly for patients in the intervention group (from 37% to 18%).

The relative risk of death among all patients who scored greater than 10 on the HADS was 50% higher, compared with patients who scored 7-10 or less than 7.

Patients in the intervention group who scored less than 10 on the HADS had a 25% relative risk reduction of death, compared with their counterparts in the usual-care group, whereas patients in the intervention group who scored greater than 10 on the HADS had a 17% relative risk reduction of death, compared with their counterparts in the usual-care group.

The multidisciplinary intervention improved the prognosis of heart failure, “even in the group of patients with clinically relevant depression,” Dr. Mareev concluded.

The results support the recent findings of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial, which found that a nonmedical intervention by a specially trained nurse improved prognosis and matched the efficacy of sertraline (J. Am. Coll. Cardiol. 2010;56:692-9). At the meeting, the one of the investigators of that trial, Dr. Christopher M. O’Connor of Duke University in Durham, N.C., said that the CHANCE study “confirms that depression is an important risk factor and confers an increased risk in morbidity and mortality” in heart failure. “This is an important advance in the field. We need more long-term studies like this.”

Dr. Mareev said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Patients with heart failure on optimal medical therapy who received a multidisciplinary, nonpharmacologic intervention for follow-up care and observation had a 38% reduction in death and rehospitalization for heart failure at 1 year, compared with patients who received usual care.

They also experienced significant improvements in depression scores from baseline, compared with their counterparts, Dr. Viacheslav Mareev reported at the annual meeting of the Heart Failure Society of America.

“It’s well known that many patients with congestive heart failure have depression,” said Dr. Mareev of the Russian Society of Heart Failure Specialists, Moscow. A recent meta-analysis of trials studying the association found that the prevalence ranges from 19% to 34%, and that the prevalence of depression worsens as heart failure worsens (J. Am. Coll. Cardiol. 2006;48:1527-37).

For the current trial, known as CHANCE (Congestive Heart Failure: A Multidisciplinary Nonpharmacological Approach for Changing in Rehospitalization and Prognosis), Dr. Mareev and his associates at 38 sites in 24 cities in Russia randomized 385 patients with New York Heart Association class III or IV heart failure to receive optimal medical treatment plus usual care, and 360 patients to receive optimal medical treatment plus education and observation by a multidisciplinary team of clinicians.

Patients in the intervention group attended four 30-minute, in-hospital educational sessions about how to live optimally with heart failure. After discharge, bilateral phone contact was made once weekly during the first month, twice a month until month 6, and then monthly until month 12. To date, none of the patients has been lost to follow-up, Dr. Mareev said.

Both groups of patients completed the HADS (Hospital Anxiety and Depression Scale) at baseline and at 12 months. In this scale, a score of less than 7 suggests the absence of anxiety and/or depression, a score of 7-10 suggests subclinical or minor anxiety and/or depression, and a score greater than 10 suggests clinically relevant, severe anxiety and/or depression.

The mean age of the study participants was 63 years, 60% were male, and 72% had NYHA class III heart failure.

Dr. Mareev reported that patients in the intervention group had a 38% reduction in death and rehospitalization for heart failure, compared with patients in the usual-care group.

Baseline HADS scores in the intervention group fell significantly (from 9.7 at baseline to 7.1 at 1 year), whereas scores in the usual-care group dropped slightly but not significantly (from 9.3 to 8.7). Dr. Mareev said that the number of patients who scored greater than 10 on the HADS dropped slightly between baseline and 1 year for patients in the usual-care group (from 31% to 30%), but dropped markedly for patients in the intervention group (from 37% to 18%).

The relative risk of death among all patients who scored greater than 10 on the HADS was 50% higher, compared with patients who scored 7-10 or less than 7.

Patients in the intervention group who scored less than 10 on the HADS had a 25% relative risk reduction of death, compared with their counterparts in the usual-care group, whereas patients in the intervention group who scored greater than 10 on the HADS had a 17% relative risk reduction of death, compared with their counterparts in the usual-care group.

The multidisciplinary intervention improved the prognosis of heart failure, “even in the group of patients with clinically relevant depression,” Dr. Mareev concluded.

The results support the recent findings of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial, which found that a nonmedical intervention by a specially trained nurse improved prognosis and matched the efficacy of sertraline (J. Am. Coll. Cardiol. 2010;56:692-9). At the meeting, the one of the investigators of that trial, Dr. Christopher M. O’Connor of Duke University in Durham, N.C., said that the CHANCE study “confirms that depression is an important risk factor and confers an increased risk in morbidity and mortality” in heart failure. “This is an important advance in the field. We need more long-term studies like this.”

Dr. Mareev said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Patients with heart failure on optimal medical therapy who received a multidisciplinary, nonpharmacologic intervention for follow-up care and observation had a 38% reduction in death and rehospitalization for heart failure at 1 year, compared with patients who received usual care.

They also experienced significant improvements in depression scores from baseline, compared with their counterparts, Dr. Viacheslav Mareev reported at the annual meeting of the Heart Failure Society of America.

“It’s well known that many patients with congestive heart failure have depression,” said Dr. Mareev of the Russian Society of Heart Failure Specialists, Moscow. A recent meta-analysis of trials studying the association found that the prevalence ranges from 19% to 34%, and that the prevalence of depression worsens as heart failure worsens (J. Am. Coll. Cardiol. 2006;48:1527-37).

For the current trial, known as CHANCE (Congestive Heart Failure: A Multidisciplinary Nonpharmacological Approach for Changing in Rehospitalization and Prognosis), Dr. Mareev and his associates at 38 sites in 24 cities in Russia randomized 385 patients with New York Heart Association class III or IV heart failure to receive optimal medical treatment plus usual care, and 360 patients to receive optimal medical treatment plus education and observation by a multidisciplinary team of clinicians.

Patients in the intervention group attended four 30-minute, in-hospital educational sessions about how to live optimally with heart failure. After discharge, bilateral phone contact was made once weekly during the first month, twice a month until month 6, and then monthly until month 12. To date, none of the patients has been lost to follow-up, Dr. Mareev said.

Both groups of patients completed the HADS (Hospital Anxiety and Depression Scale) at baseline and at 12 months. In this scale, a score of less than 7 suggests the absence of anxiety and/or depression, a score of 7-10 suggests subclinical or minor anxiety and/or depression, and a score greater than 10 suggests clinically relevant, severe anxiety and/or depression.

The mean age of the study participants was 63 years, 60% were male, and 72% had NYHA class III heart failure.

Dr. Mareev reported that patients in the intervention group had a 38% reduction in death and rehospitalization for heart failure, compared with patients in the usual-care group.

Baseline HADS scores in the intervention group fell significantly (from 9.7 at baseline to 7.1 at 1 year), whereas scores in the usual-care group dropped slightly but not significantly (from 9.3 to 8.7). Dr. Mareev said that the number of patients who scored greater than 10 on the HADS dropped slightly between baseline and 1 year for patients in the usual-care group (from 31% to 30%), but dropped markedly for patients in the intervention group (from 37% to 18%).

The relative risk of death among all patients who scored greater than 10 on the HADS was 50% higher, compared with patients who scored 7-10 or less than 7.

Patients in the intervention group who scored less than 10 on the HADS had a 25% relative risk reduction of death, compared with their counterparts in the usual-care group, whereas patients in the intervention group who scored greater than 10 on the HADS had a 17% relative risk reduction of death, compared with their counterparts in the usual-care group.

The multidisciplinary intervention improved the prognosis of heart failure, “even in the group of patients with clinically relevant depression,” Dr. Mareev concluded.

The results support the recent findings of the SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial, which found that a nonmedical intervention by a specially trained nurse improved prognosis and matched the efficacy of sertraline (J. Am. Coll. Cardiol. 2010;56:692-9). At the meeting, the one of the investigators of that trial, Dr. Christopher M. O’Connor of Duke University in Durham, N.C., said that the CHANCE study “confirms that depression is an important risk factor and confers an increased risk in morbidity and mortality” in heart failure. “This is an important advance in the field. We need more long-term studies like this.”

Dr. Mareev said that he had no relevant financial conflicts to disclose.

SANTA BARBARA, Calif. – Current American Joint Committee on Cancer melanoma staging criteria incorporate a mitotic rate of 1/mm2 or greater into the T1b classification, recognizing mitotic rate as an independent prognostic factor in patients with primary melanoma.

This change, which went into effect in January,"is going to have a profound impact in whom we consider eligible for staging with sentinel lymph node biopsy" Dr. Susan Swetter predicted at the annual meeting of the California Society of Dermatology and Dermatologic Surgery. "The reason is that only about 6%-8% of these T1 tumors (1.0 mm) are ulcerated, but it is estimated that up to 30%-40% will have an elevated mitotic rate of 1.0 or more per square millimeter. This leaves us with a conundrum: Are all of these patients going to be eligible for sentinel lymph node biopsy?"

Current AJCC melanoma staging criteria are based on data analysis from the 2008 AJCC collaborative melanoma staging database from 14 cancer centers and cooperative oncology organizations worldwide, said Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford University Medical Center/VA Palo Alto Health Care System, Calif.

The criteria are based on prognostic factor analysis of nearly 60,000 patients to validate staging criteria and groupings for the 7th edition of the AJCC Cancer Staging Manual (Springer, New York), which was published in the fall of 2009 and became active in January 2010.

"The concept is that each stage grouping has a uniform risk for survival, and there are a wealth of patients per tumor node metastasis (TNM) categories, with more than 27,000 with stage I and II disease, more than 3,400 with stage III disease, and more than 7,600 with stage IV disease," Dr. Swetter said.

The newest revision of the AJCC staging for melanoma involves no major changes for TNM and stage grouping criteria, with the exception of mitotic rate.

Other changes involve more advanced disease. For example, "immunohistochemical detection of nodal metastases is now acceptable, whereas only routine histology was used previously," Dr. Swetter said. "Also, there is no longer a lower limit to designate node-positive disease. The size of the isolated tumor cells is no longer used, although that is quite controversial."

Thickness of tumors is potentially a marker of duration of growth, with increasing tumor thickness correlating adversely with survival. According to the 2008 AJCC Melanoma Database, patients with tumor thickness of 0.01-0.55 mm have a 10-year survival rate of 95%, while those with a tumor thickness of 4.01-6.0 mm have a 10-year survival rate of 54%.

The most relevant correlate of a mitotic rate increase and its effect on prognosis appears to be in thin tumors, Dr. Swetter said. "This is why the new AJCC guidelines incorporate mitotic rate in tumors that are less than or equal to 1.0 mm thick."

Survival data from the 2008 AJCC Melanoma Database suggest there is little to no value in promoting sentinel lymph node biopsy in patients who have tumors up to 0.50 mm in depth, regardless of mitotic rate, because the survival rate in these patients is excellent. Currently, the T1b designation is used for staging in terms of survival. "It is not a criterion in itself to perform sentinel lymph node biopsy," Dr. Swetter emphasized. "There is some evolving data suggesting that mitotic rate as a continuous variable may be predictive of occult regional nodal disease."

One published study suggests that sentinel lymph node biopsy is appropriate for patients with T1b melanomas, including those defined by mitotic rate (J. Natl. Compr. Canc. Netw. 2009;7:308-17). "We are now awaiting publication of a larger analysis of patients with thin melanoma," Dr. Swetter said. "Both the National Comprehensive Cancer Network and the AAD [American Academy of Dermatology] melanoma panels are weighing in to establish an appropriate threshold in these T1b patients."

Dr. Swetter, who serves on both of the panels, noted that there is currently "very little enthusiasm from a surgical perspective to be pursuing sentinel lymph node biopsy on every patient who is T1b by virtue of mitotic rate."

The National Comprehensive Cancer Network recommends that clinicians "discuss and offer" sentinel lymph node biopsy for patients with stage IB and stage II cutaneous melanoma, "recognizing that the sentinel node biopsy is an important staging tool, but its impact on overall survival is unclear," Dr. Swetter said.

The procedure should also be considered for stage IA melanomas with adverse features including positive deep margins, lymphovascular invasion, thickness of 0.75 mm or greater, or younger age.

The decision not to perform sentinel lymph node biopsy can be based on significant patient comorbidities, patient preference, or other factors.

An unresolved question is whether or not sentinel lymph node biopsy is a valid staging technique in older patients. "Older age is associated with worse prognosis, but lower rates of sentinel lymph node positivity," Dr. Swetter said. "The question is, why? One issue is whether there is different biology of melanoma in the elderly, or whether host immune factors come into play. Another [factor] could be delayed lymphatic spread, or it might be that tumors are more likely to disseminate hematogenously in older patients, compared with younger patients."

In the future, Dr. Swetter predicted the emergence of individualized prognoses based on novel weighted mathematical equations using AJCC staging and other factors. A Web-based predictive tool for prognosis developed by the AJCC Melanoma Database is currently available at www.melanomaprognosis.org.

Dr. Swetter stated having no relevant financial conflicts to disclose.

SANTA BARBARA, Calif. – Current American Joint Committee on Cancer melanoma staging criteria incorporate a mitotic rate of 1/mm2 or greater into the T1b classification, recognizing mitotic rate as an independent prognostic factor in patients with primary melanoma.

This change, which went into effect in January,"is going to have a profound impact in whom we consider eligible for staging with sentinel lymph node biopsy" Dr. Susan Swetter predicted at the annual meeting of the California Society of Dermatology and Dermatologic Surgery. "The reason is that only about 6%-8% of these T1 tumors (1.0 mm) are ulcerated, but it is estimated that up to 30%-40% will have an elevated mitotic rate of 1.0 or more per square millimeter. This leaves us with a conundrum: Are all of these patients going to be eligible for sentinel lymph node biopsy?"

Current AJCC melanoma staging criteria are based on data analysis from the 2008 AJCC collaborative melanoma staging database from 14 cancer centers and cooperative oncology organizations worldwide, said Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford University Medical Center/VA Palo Alto Health Care System, Calif.

The criteria are based on prognostic factor analysis of nearly 60,000 patients to validate staging criteria and groupings for the 7th edition of the AJCC Cancer Staging Manual (Springer, New York), which was published in the fall of 2009 and became active in January 2010.

"The concept is that each stage grouping has a uniform risk for survival, and there are a wealth of patients per tumor node metastasis (TNM) categories, with more than 27,000 with stage I and II disease, more than 3,400 with stage III disease, and more than 7,600 with stage IV disease," Dr. Swetter said.

The newest revision of the AJCC staging for melanoma involves no major changes for TNM and stage grouping criteria, with the exception of mitotic rate.

Other changes involve more advanced disease. For example, "immunohistochemical detection of nodal metastases is now acceptable, whereas only routine histology was used previously," Dr. Swetter said. "Also, there is no longer a lower limit to designate node-positive disease. The size of the isolated tumor cells is no longer used, although that is quite controversial."

Thickness of tumors is potentially a marker of duration of growth, with increasing tumor thickness correlating adversely with survival. According to the 2008 AJCC Melanoma Database, patients with tumor thickness of 0.01-0.55 mm have a 10-year survival rate of 95%, while those with a tumor thickness of 4.01-6.0 mm have a 10-year survival rate of 54%.

The most relevant correlate of a mitotic rate increase and its effect on prognosis appears to be in thin tumors, Dr. Swetter said. "This is why the new AJCC guidelines incorporate mitotic rate in tumors that are less than or equal to 1.0 mm thick."

Survival data from the 2008 AJCC Melanoma Database suggest there is little to no value in promoting sentinel lymph node biopsy in patients who have tumors up to 0.50 mm in depth, regardless of mitotic rate, because the survival rate in these patients is excellent. Currently, the T1b designation is used for staging in terms of survival. "It is not a criterion in itself to perform sentinel lymph node biopsy," Dr. Swetter emphasized. "There is some evolving data suggesting that mitotic rate as a continuous variable may be predictive of occult regional nodal disease."

One published study suggests that sentinel lymph node biopsy is appropriate for patients with T1b melanomas, including those defined by mitotic rate (J. Natl. Compr. Canc. Netw. 2009;7:308-17). "We are now awaiting publication of a larger analysis of patients with thin melanoma," Dr. Swetter said. "Both the National Comprehensive Cancer Network and the AAD [American Academy of Dermatology] melanoma panels are weighing in to establish an appropriate threshold in these T1b patients."

Dr. Swetter, who serves on both of the panels, noted that there is currently "very little enthusiasm from a surgical perspective to be pursuing sentinel lymph node biopsy on every patient who is T1b by virtue of mitotic rate."

The National Comprehensive Cancer Network recommends that clinicians "discuss and offer" sentinel lymph node biopsy for patients with stage IB and stage II cutaneous melanoma, "recognizing that the sentinel node biopsy is an important staging tool, but its impact on overall survival is unclear," Dr. Swetter said.

The procedure should also be considered for stage IA melanomas with adverse features including positive deep margins, lymphovascular invasion, thickness of 0.75 mm or greater, or younger age.

The decision not to perform sentinel lymph node biopsy can be based on significant patient comorbidities, patient preference, or other factors.

An unresolved question is whether or not sentinel lymph node biopsy is a valid staging technique in older patients. "Older age is associated with worse prognosis, but lower rates of sentinel lymph node positivity," Dr. Swetter said. "The question is, why? One issue is whether there is different biology of melanoma in the elderly, or whether host immune factors come into play. Another [factor] could be delayed lymphatic spread, or it might be that tumors are more likely to disseminate hematogenously in older patients, compared with younger patients."

In the future, Dr. Swetter predicted the emergence of individualized prognoses based on novel weighted mathematical equations using AJCC staging and other factors. A Web-based predictive tool for prognosis developed by the AJCC Melanoma Database is currently available at www.melanomaprognosis.org.

Dr. Swetter stated having no relevant financial conflicts to disclose.

SANTA BARBARA, Calif. – Current American Joint Committee on Cancer melanoma staging criteria incorporate a mitotic rate of 1/mm2 or greater into the T1b classification, recognizing mitotic rate as an independent prognostic factor in patients with primary melanoma.

This change, which went into effect in January,"is going to have a profound impact in whom we consider eligible for staging with sentinel lymph node biopsy" Dr. Susan Swetter predicted at the annual meeting of the California Society of Dermatology and Dermatologic Surgery. "The reason is that only about 6%-8% of these T1 tumors (1.0 mm) are ulcerated, but it is estimated that up to 30%-40% will have an elevated mitotic rate of 1.0 or more per square millimeter. This leaves us with a conundrum: Are all of these patients going to be eligible for sentinel lymph node biopsy?"

Current AJCC melanoma staging criteria are based on data analysis from the 2008 AJCC collaborative melanoma staging database from 14 cancer centers and cooperative oncology organizations worldwide, said Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford University Medical Center/VA Palo Alto Health Care System, Calif.

The criteria are based on prognostic factor analysis of nearly 60,000 patients to validate staging criteria and groupings for the 7th edition of the AJCC Cancer Staging Manual (Springer, New York), which was published in the fall of 2009 and became active in January 2010.

"The concept is that each stage grouping has a uniform risk for survival, and there are a wealth of patients per tumor node metastasis (TNM) categories, with more than 27,000 with stage I and II disease, more than 3,400 with stage III disease, and more than 7,600 with stage IV disease," Dr. Swetter said.

The newest revision of the AJCC staging for melanoma involves no major changes for TNM and stage grouping criteria, with the exception of mitotic rate.

Other changes involve more advanced disease. For example, "immunohistochemical detection of nodal metastases is now acceptable, whereas only routine histology was used previously," Dr. Swetter said. "Also, there is no longer a lower limit to designate node-positive disease. The size of the isolated tumor cells is no longer used, although that is quite controversial."

Thickness of tumors is potentially a marker of duration of growth, with increasing tumor thickness correlating adversely with survival. According to the 2008 AJCC Melanoma Database, patients with tumor thickness of 0.01-0.55 mm have a 10-year survival rate of 95%, while those with a tumor thickness of 4.01-6.0 mm have a 10-year survival rate of 54%.

The most relevant correlate of a mitotic rate increase and its effect on prognosis appears to be in thin tumors, Dr. Swetter said. "This is why the new AJCC guidelines incorporate mitotic rate in tumors that are less than or equal to 1.0 mm thick."

Survival data from the 2008 AJCC Melanoma Database suggest there is little to no value in promoting sentinel lymph node biopsy in patients who have tumors up to 0.50 mm in depth, regardless of mitotic rate, because the survival rate in these patients is excellent. Currently, the T1b designation is used for staging in terms of survival. "It is not a criterion in itself to perform sentinel lymph node biopsy," Dr. Swetter emphasized. "There is some evolving data suggesting that mitotic rate as a continuous variable may be predictive of occult regional nodal disease."

One published study suggests that sentinel lymph node biopsy is appropriate for patients with T1b melanomas, including those defined by mitotic rate (J. Natl. Compr. Canc. Netw. 2009;7:308-17). "We are now awaiting publication of a larger analysis of patients with thin melanoma," Dr. Swetter said. "Both the National Comprehensive Cancer Network and the AAD [American Academy of Dermatology] melanoma panels are weighing in to establish an appropriate threshold in these T1b patients."

Dr. Swetter, who serves on both of the panels, noted that there is currently "very little enthusiasm from a surgical perspective to be pursuing sentinel lymph node biopsy on every patient who is T1b by virtue of mitotic rate."

The National Comprehensive Cancer Network recommends that clinicians "discuss and offer" sentinel lymph node biopsy for patients with stage IB and stage II cutaneous melanoma, "recognizing that the sentinel node biopsy is an important staging tool, but its impact on overall survival is unclear," Dr. Swetter said.

The procedure should also be considered for stage IA melanomas with adverse features including positive deep margins, lymphovascular invasion, thickness of 0.75 mm or greater, or younger age.

The decision not to perform sentinel lymph node biopsy can be based on significant patient comorbidities, patient preference, or other factors.

An unresolved question is whether or not sentinel lymph node biopsy is a valid staging technique in older patients. "Older age is associated with worse prognosis, but lower rates of sentinel lymph node positivity," Dr. Swetter said. "The question is, why? One issue is whether there is different biology of melanoma in the elderly, or whether host immune factors come into play. Another [factor] could be delayed lymphatic spread, or it might be that tumors are more likely to disseminate hematogenously in older patients, compared with younger patients."

In the future, Dr. Swetter predicted the emergence of individualized prognoses based on novel weighted mathematical equations using AJCC staging and other factors. A Web-based predictive tool for prognosis developed by the AJCC Melanoma Database is currently available at www.melanomaprognosis.org.

Dr. Swetter stated having no relevant financial conflicts to disclose.

SANTA BARBARA, Calif. – Current American Joint Committee on Cancer melanoma staging criteria incorporate a mitotic rate of 1/mm2 or greater into the T1b classification, recognizing mitotic rate as an independent prognostic factor in patients with primary melanoma.

This change, which went into effect in January,“is going to have a profound impact in whom we consider eligible for staging with sentinel lymph node biopsy,” Dr. Susan Swetter predicted at the annual meeting of the California Society of Dermatology and Dermatologic Surgery. “The reason is that only about 6%-8% of these T1 tumors (1.0 mm) are ulcerated, but it is estimated that up to 30%-40% will have an elevated mitotic rate of 1.0 or more per square millimeter. This leaves us with a conundrum: Are all of these patients going to be eligible for sentinel lymph node biopsy?”

Current AJCC melanoma staging criteria are based on data analysis from the 2008 AJCC collaborative melanoma staging database from 14 cancer centers and cooperative oncology organizations worldwide, said Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford University Medical Center/VA Palo Alto Health Care System, Calif.

The criteria are based on prognostic factor analysis of nearly 60,000 patients to validate staging criteria and groupings for the 7th edition of the AJCC Cancer Staging Manual (Springer, New York), which was published in the fall of 2009 and became active in January 2010.

“The concept is that each stage grouping has a uniform risk for survival, and there are a wealth of patients per tumor node metastasis (TNM) categories, with more than 27,000 with stage I and II disease, more than 3,400 with stage III disease, and more than 7,600 with stage IV disease,” Dr. Swetter said.

The newest revision of the AJCC staging for melanoma involves no major changes for TNM and stage grouping criteria, with the exception of mitotic rate.

Other changes involve more advanced disease. For example, “immunohistochemical detection of nodal metastases is now acceptable, whereas only routine histology was used previously,” Dr. Swetter said. “Also, there is no longer a lower limit to designate node-positive disease. The size of the isolated tumor cells is no longer used, although that is quite controversial.”

Thickness of tumors is potentially a marker of duration of growth, with increasing tumor thickness correlating adversely with survival. According to the 2008 AJCC Melanoma Database, patients with tumor thickness of 0.01-0.55 mm have a 10-year survival rate of 95%, while those with a tumor thickness of 4.01-6.0 mm have a 10-year survival rate of 54%.

The most relevant correlate of a mitotic rate increase and its effect on prognosis appears to be in thin tumors, Dr. Swetter said. “This is why the new AJCC guidelines incorporate mitotic rate in tumors that are less than or equal to 1.0 mm thick.”

Survival data from the 2008 AJCC Melanoma Database suggest there is little to no value in promoting sentinel lymph node biopsy in patients who have tumors up to 0.50 mm in depth, regardless of mitotic rate, because the survival rate in these patients is excellent. Currently, the T1b designation is used for staging in terms of survival. “It is not a criterion in itself to perform sentinel lymph node biopsy,” Dr. Swetter emphasized. “There is some evolving data suggesting that mitotic rate as a continuous variable may be predictive of occult regional nodal disease.”

One published study suggests that sentinel lymph node biopsy is appropriate for patients with T1b melanomas, including those defined by mitotic rate (J. Natl. Compr. Canc. Netw. 2009;7:308-17). “We are now awaiting publication of a larger analysis of patients with thin melanoma,” Dr. Swetter said. “Both the National Comprehensive Cancer Network and the AAD [American Academy of Dermatology] melanoma panels are weighing in to establish an appropriate threshold in these T1b patients.”

Dr. Swetter, who serves on both of the panels, noted that there is currently “very little enthusiasm from a surgical perspective to be pursuing sentinel lymph node biopsy on every patient who is T1b by virtue of mitotic rate.”

The National Comprehensive Cancer Network recommends that clinicians “discuss and offer” sentinel lymph node biopsy for patients with stage IB and stage II cutaneous melanoma, “recognizing that the sentinel node biopsy is an important staging tool, but its impact on overall survival is unclear,” Dr. Swetter said.

The procedure should also be considered for stage IA melanomas with adverse features including positive deep margins, lymphovascular invasion, thickness of 0.75 mm or greater, or younger age.

The decision not to perform sentinel lymph node biopsy can be based on significant patient comorbidities, patient preference, or other factors.

An unresolved question is whether or not sentinel lymph node biopsy is a valid staging technique in older patients. “Older age is associated with worse prognosis, but lower rates of sentinel lymph node positivity,” Dr. Swetter said. “The question is, why? One issue is whether there is different biology of melanoma in the elderly, or whether host immune factors come into play. Another [factor] could be delayed lymphatic spread, or it might be that tumors are more likely to disseminate hematogenously in older patients, compared with younger patients.”

In the future, Dr. Swetter predicted the emergence of individualized prognoses based on novel weighted mathematical equations using AJCC staging and other factors. A Web-based predictive tool for prognosis developed by the AJCC Melanoma Database is currently available at www.melanomaprognosis.org.

Dr. Swetter stated having no relevant financial conflicts to disclose.

SANTA BARBARA, Calif. – Current American Joint Committee on Cancer melanoma staging criteria incorporate a mitotic rate of 1/mm2 or greater into the T1b classification, recognizing mitotic rate as an independent prognostic factor in patients with primary melanoma.

This change, which went into effect in January,“is going to have a profound impact in whom we consider eligible for staging with sentinel lymph node biopsy,” Dr. Susan Swetter predicted at the annual meeting of the California Society of Dermatology and Dermatologic Surgery. “The reason is that only about 6%-8% of these T1 tumors (1.0 mm) are ulcerated, but it is estimated that up to 30%-40% will have an elevated mitotic rate of 1.0 or more per square millimeter. This leaves us with a conundrum: Are all of these patients going to be eligible for sentinel lymph node biopsy?”

Current AJCC melanoma staging criteria are based on data analysis from the 2008 AJCC collaborative melanoma staging database from 14 cancer centers and cooperative oncology organizations worldwide, said Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford University Medical Center/VA Palo Alto Health Care System, Calif.

The criteria are based on prognostic factor analysis of nearly 60,000 patients to validate staging criteria and groupings for the 7th edition of the AJCC Cancer Staging Manual (Springer, New York), which was published in the fall of 2009 and became active in January 2010.

“The concept is that each stage grouping has a uniform risk for survival, and there are a wealth of patients per tumor node metastasis (TNM) categories, with more than 27,000 with stage I and II disease, more than 3,400 with stage III disease, and more than 7,600 with stage IV disease,” Dr. Swetter said.

The newest revision of the AJCC staging for melanoma involves no major changes for TNM and stage grouping criteria, with the exception of mitotic rate.

Other changes involve more advanced disease. For example, “immunohistochemical detection of nodal metastases is now acceptable, whereas only routine histology was used previously,” Dr. Swetter said. “Also, there is no longer a lower limit to designate node-positive disease. The size of the isolated tumor cells is no longer used, although that is quite controversial.”

Thickness of tumors is potentially a marker of duration of growth, with increasing tumor thickness correlating adversely with survival. According to the 2008 AJCC Melanoma Database, patients with tumor thickness of 0.01-0.55 mm have a 10-year survival rate of 95%, while those with a tumor thickness of 4.01-6.0 mm have a 10-year survival rate of 54%.

The most relevant correlate of a mitotic rate increase and its effect on prognosis appears to be in thin tumors, Dr. Swetter said. “This is why the new AJCC guidelines incorporate mitotic rate in tumors that are less than or equal to 1.0 mm thick.”

Survival data from the 2008 AJCC Melanoma Database suggest there is little to no value in promoting sentinel lymph node biopsy in patients who have tumors up to 0.50 mm in depth, regardless of mitotic rate, because the survival rate in these patients is excellent. Currently, the T1b designation is used for staging in terms of survival. “It is not a criterion in itself to perform sentinel lymph node biopsy,” Dr. Swetter emphasized. “There is some evolving data suggesting that mitotic rate as a continuous variable may be predictive of occult regional nodal disease.”

One published study suggests that sentinel lymph node biopsy is appropriate for patients with T1b melanomas, including those defined by mitotic rate (J. Natl. Compr. Canc. Netw. 2009;7:308-17). “We are now awaiting publication of a larger analysis of patients with thin melanoma,” Dr. Swetter said. “Both the National Comprehensive Cancer Network and the AAD [American Academy of Dermatology] melanoma panels are weighing in to establish an appropriate threshold in these T1b patients.”

Dr. Swetter, who serves on both of the panels, noted that there is currently “very little enthusiasm from a surgical perspective to be pursuing sentinel lymph node biopsy on every patient who is T1b by virtue of mitotic rate.”

The National Comprehensive Cancer Network recommends that clinicians “discuss and offer” sentinel lymph node biopsy for patients with stage IB and stage II cutaneous melanoma, “recognizing that the sentinel node biopsy is an important staging tool, but its impact on overall survival is unclear,” Dr. Swetter said.

The procedure should also be considered for stage IA melanomas with adverse features including positive deep margins, lymphovascular invasion, thickness of 0.75 mm or greater, or younger age.

The decision not to perform sentinel lymph node biopsy can be based on significant patient comorbidities, patient preference, or other factors.

An unresolved question is whether or not sentinel lymph node biopsy is a valid staging technique in older patients. “Older age is associated with worse prognosis, but lower rates of sentinel lymph node positivity,” Dr. Swetter said. “The question is, why? One issue is whether there is different biology of melanoma in the elderly, or whether host immune factors come into play. Another [factor] could be delayed lymphatic spread, or it might be that tumors are more likely to disseminate hematogenously in older patients, compared with younger patients.”

In the future, Dr. Swetter predicted the emergence of individualized prognoses based on novel weighted mathematical equations using AJCC staging and other factors. A Web-based predictive tool for prognosis developed by the AJCC Melanoma Database is currently available at www.melanomaprognosis.org.

Dr. Swetter stated having no relevant financial conflicts to disclose.

SANTA BARBARA, Calif. – Current American Joint Committee on Cancer melanoma staging criteria incorporate a mitotic rate of 1/mm2 or greater into the T1b classification, recognizing mitotic rate as an independent prognostic factor in patients with primary melanoma.

This change, which went into effect in January,“is going to have a profound impact in whom we consider eligible for staging with sentinel lymph node biopsy,” Dr. Susan Swetter predicted at the annual meeting of the California Society of Dermatology and Dermatologic Surgery. “The reason is that only about 6%-8% of these T1 tumors (1.0 mm) are ulcerated, but it is estimated that up to 30%-40% will have an elevated mitotic rate of 1.0 or more per square millimeter. This leaves us with a conundrum: Are all of these patients going to be eligible for sentinel lymph node biopsy?”

Current AJCC melanoma staging criteria are based on data analysis from the 2008 AJCC collaborative melanoma staging database from 14 cancer centers and cooperative oncology organizations worldwide, said Dr. Swetter, professor of dermatology and director of the pigmented lesion and melanoma program at Stanford University Medical Center/VA Palo Alto Health Care System, Calif.

The criteria are based on prognostic factor analysis of nearly 60,000 patients to validate staging criteria and groupings for the 7th edition of the AJCC Cancer Staging Manual (Springer, New York), which was published in the fall of 2009 and became active in January 2010.

“The concept is that each stage grouping has a uniform risk for survival, and there are a wealth of patients per tumor node metastasis (TNM) categories, with more than 27,000 with stage I and II disease, more than 3,400 with stage III disease, and more than 7,600 with stage IV disease,” Dr. Swetter said.

The newest revision of the AJCC staging for melanoma involves no major changes for TNM and stage grouping criteria, with the exception of mitotic rate.

Other changes involve more advanced disease. For example, “immunohistochemical detection of nodal metastases is now acceptable, whereas only routine histology was used previously,” Dr. Swetter said. “Also, there is no longer a lower limit to designate node-positive disease. The size of the isolated tumor cells is no longer used, although that is quite controversial.”

Thickness of tumors is potentially a marker of duration of growth, with increasing tumor thickness correlating adversely with survival. According to the 2008 AJCC Melanoma Database, patients with tumor thickness of 0.01-0.55 mm have a 10-year survival rate of 95%, while those with a tumor thickness of 4.01-6.0 mm have a 10-year survival rate of 54%.

The most relevant correlate of a mitotic rate increase and its effect on prognosis appears to be in thin tumors, Dr. Swetter said. “This is why the new AJCC guidelines incorporate mitotic rate in tumors that are less than or equal to 1.0 mm thick.”

Survival data from the 2008 AJCC Melanoma Database suggest there is little to no value in promoting sentinel lymph node biopsy in patients who have tumors up to 0.50 mm in depth, regardless of mitotic rate, because the survival rate in these patients is excellent. Currently, the T1b designation is used for staging in terms of survival. “It is not a criterion in itself to perform sentinel lymph node biopsy,” Dr. Swetter emphasized. “There is some evolving data suggesting that mitotic rate as a continuous variable may be predictive of occult regional nodal disease.”

One published study suggests that sentinel lymph node biopsy is appropriate for patients with T1b melanomas, including those defined by mitotic rate (J. Natl. Compr. Canc. Netw. 2009;7:308-17). “We are now awaiting publication of a larger analysis of patients with thin melanoma,” Dr. Swetter said. “Both the National Comprehensive Cancer Network and the AAD [American Academy of Dermatology] melanoma panels are weighing in to establish an appropriate threshold in these T1b patients.”

Dr. Swetter, who serves on both of the panels, noted that there is currently “very little enthusiasm from a surgical perspective to be pursuing sentinel lymph node biopsy on every patient who is T1b by virtue of mitotic rate.”

The National Comprehensive Cancer Network recommends that clinicians “discuss and offer” sentinel lymph node biopsy for patients with stage IB and stage II cutaneous melanoma, “recognizing that the sentinel node biopsy is an important staging tool, but its impact on overall survival is unclear,” Dr. Swetter said.

The procedure should also be considered for stage IA melanomas with adverse features including positive deep margins, lymphovascular invasion, thickness of 0.75 mm or greater, or younger age.

The decision not to perform sentinel lymph node biopsy can be based on significant patient comorbidities, patient preference, or other factors.

An unresolved question is whether or not sentinel lymph node biopsy is a valid staging technique in older patients. “Older age is associated with worse prognosis, but lower rates of sentinel lymph node positivity,” Dr. Swetter said. “The question is, why? One issue is whether there is different biology of melanoma in the elderly, or whether host immune factors come into play. Another [factor] could be delayed lymphatic spread, or it might be that tumors are more likely to disseminate hematogenously in older patients, compared with younger patients.”

In the future, Dr. Swetter predicted the emergence of individualized prognoses based on novel weighted mathematical equations using AJCC staging and other factors. A Web-based predictive tool for prognosis developed by the AJCC Melanoma Database is currently available at www.melanomaprognosis.org.

Dr. Swetter stated having no relevant financial conflicts to disclose.

SAN DIEGO – In a phase II study of patients with advanced heart failure, gene therapy with MYDICAR was found to be safe and was associated with benefit in clinical outcomes, symptoms, functional status, and cardiac structure.

Deficiency of the protein SERCA2a is central to the progression of heart failure, resulting in abnormal calcium transfer and impairing myocardial relaxation and contraction, Dr. Barry H. Greenberg said at the annual meeting of the Heart Failure Society of America.

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A recombinant adeno-associated viral vector is used to deliver the SERCA2a gene.

The objectives of the phase II study, known as CUPID (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease), were to evaluate safety and feasibility and to explore the activity and efficacy of MYDICAR in patients with advanced heart failure, said Dr. Greenberg, professor of medicine and director of the Advance Heart Failure Treatment Program at the University of California, San Diego.

To be eligible for the trial, patients had to be 18-75 years old, have New York State Heart Association class III or IV heart failure caused by an ischemic or nonischemic etiology, have a maximal oxygen consumption of 20 mL/kg per minute or less, have a left ventricular fraction of 35% or less, and be on a stable, optimized heart failure regimen for 30 days.

Dr. Greenberg and his associates randomized 39 patients to one of three doses of MYDICAR or to placebo, and all were treated via single intracoronary infusion. All patients were observed for 12 months, with a primary analysis after 6 months of therapy.

The mean age of patients was 61 years, 87% were male, 87% were white, half had heart failure resulting from ischemic cardiomyopathy, and all had NYHA class III heart failure.

Safety measurements included physical examination, electrocardiogram, adverse events, complete blood count, serum chemistries, urinalysis, creatine kinase myocardial band, troponin T, and enzyme-linked immunospot testing for cellular immune response against viral proteins.

Efficacy domains included symptomatic changes in NYHA class and the MLHF (Minnesota Living With Heart Failure) questionnaire; functional changes based on 6-minute walk test and maximal oxygen consumption; changes in N-terminal prohormone brain natriuretic peptide; and evidence of remodeling based on ejection fraction scores and end systolic volume.

CUPID’s primary efficacy end point was defined as evidence of success in one of four areas: group-level analysis, individual analysis, time-to-event analysis, and duration of cardiovascular-related hospitalization analysis. All were deemed statistically significant (P less than .2).

CUPID met the primary efficacy end point for high-dose MYDICAR treatment group vs. placebo in three of the four areas. In the group-level analysis, significant improvements were seen in the treatment group, compared with the placebo group, in improvements in the 6-minute walk test and end systolic volume, with no clinically significant worsening in any end point and numerical superiority to placebo in all other end points.

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group.

In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but this difference did not reach statistical significance.

In the duration of cardiovascular-related hospitalization analysis, the duration of stay was significantly shorter for patients in the treatment group, compared with the placebo group (mean, 2 fewer days).

Dr. Greenberg reported that there were no statistically significant differences between the treatment groups and the placebo groups in the proportion of adverse events or serious events.

“These encouraging results support further studies to determine the value of genetically targeted enzyme replacement of SERCA2a in advanced heart failure,” Dr. Greenberg concluded.

The meeting’s invited discussant, Dr. Michael R. Bristow, president and CEO of ARCA Biopharma Inc., described it as “a big deal to have done gene therapy on this number of patients who are this sick and see absolutely no evidence of safety concern. I believe there’s definite evidence of an efficacy signal ... [and] that CUPID will serve as a catalyst for the development of other gene therapies for heart failure.”

Disclosures: Celladon Corp. funded the trial. Dr. Greenberg said that he had no relevant financial disclosures to make.

SAN DIEGO – In a phase II study of patients with advanced heart failure, gene therapy with MYDICAR was found to be safe and was associated with benefit in clinical outcomes, symptoms, functional status, and cardiac structure.

Deficiency of the protein SERCA2a is central to the progression of heart failure, resulting in abnormal calcium transfer and impairing myocardial relaxation and contraction, Dr. Barry H. Greenberg said at the annual meeting of the Heart Failure Society of America.

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A recombinant adeno-associated viral vector is used to deliver the SERCA2a gene.

The objectives of the phase II study, known as CUPID (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease), were to evaluate safety and feasibility and to explore the activity and efficacy of MYDICAR in patients with advanced heart failure, said Dr. Greenberg, professor of medicine and director of the Advance Heart Failure Treatment Program at the University of California, San Diego.

To be eligible for the trial, patients had to be 18-75 years old, have New York State Heart Association class III or IV heart failure caused by an ischemic or nonischemic etiology, have a maximal oxygen consumption of 20 mL/kg per minute or less, have a left ventricular fraction of 35% or less, and be on a stable, optimized heart failure regimen for 30 days.

Dr. Greenberg and his associates randomized 39 patients to one of three doses of MYDICAR or to placebo, and all were treated via single intracoronary infusion. All patients were observed for 12 months, with a primary analysis after 6 months of therapy.

The mean age of patients was 61 years, 87% were male, 87% were white, half had heart failure resulting from ischemic cardiomyopathy, and all had NYHA class III heart failure.

Safety measurements included physical examination, electrocardiogram, adverse events, complete blood count, serum chemistries, urinalysis, creatine kinase myocardial band, troponin T, and enzyme-linked immunospot testing for cellular immune response against viral proteins.

Efficacy domains included symptomatic changes in NYHA class and the MLHF (Minnesota Living With Heart Failure) questionnaire; functional changes based on 6-minute walk test and maximal oxygen consumption; changes in N-terminal prohormone brain natriuretic peptide; and evidence of remodeling based on ejection fraction scores and end systolic volume.

CUPID’s primary efficacy end point was defined as evidence of success in one of four areas: group-level analysis, individual analysis, time-to-event analysis, and duration of cardiovascular-related hospitalization analysis. All were deemed statistically significant (P less than .2).

CUPID met the primary efficacy end point for high-dose MYDICAR treatment group vs. placebo in three of the four areas. In the group-level analysis, significant improvements were seen in the treatment group, compared with the placebo group, in improvements in the 6-minute walk test and end systolic volume, with no clinically significant worsening in any end point and numerical superiority to placebo in all other end points.

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group.

In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but this difference did not reach statistical significance.

In the duration of cardiovascular-related hospitalization analysis, the duration of stay was significantly shorter for patients in the treatment group, compared with the placebo group (mean, 2 fewer days).

Dr. Greenberg reported that there were no statistically significant differences between the treatment groups and the placebo groups in the proportion of adverse events or serious events.

“These encouraging results support further studies to determine the value of genetically targeted enzyme replacement of SERCA2a in advanced heart failure,” Dr. Greenberg concluded.

The meeting’s invited discussant, Dr. Michael R. Bristow, president and CEO of ARCA Biopharma Inc., described it as “a big deal to have done gene therapy on this number of patients who are this sick and see absolutely no evidence of safety concern. I believe there’s definite evidence of an efficacy signal ... [and] that CUPID will serve as a catalyst for the development of other gene therapies for heart failure.”

Disclosures: Celladon Corp. funded the trial. Dr. Greenberg said that he had no relevant financial disclosures to make.

SAN DIEGO – In a phase II study of patients with advanced heart failure, gene therapy with MYDICAR was found to be safe and was associated with benefit in clinical outcomes, symptoms, functional status, and cardiac structure.

Deficiency of the protein SERCA2a is central to the progression of heart failure, resulting in abnormal calcium transfer and impairing myocardial relaxation and contraction, Dr. Barry H. Greenberg said at the annual meeting of the Heart Failure Society of America.

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A recombinant adeno-associated viral vector is used to deliver the SERCA2a gene.

The objectives of the phase II study, known as CUPID (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease), were to evaluate safety and feasibility and to explore the activity and efficacy of MYDICAR in patients with advanced heart failure, said Dr. Greenberg, professor of medicine and director of the Advance Heart Failure Treatment Program at the University of California, San Diego.

To be eligible for the trial, patients had to be 18-75 years old, have New York State Heart Association class III or IV heart failure caused by an ischemic or nonischemic etiology, have a maximal oxygen consumption of 20 mL/kg per minute or less, have a left ventricular fraction of 35% or less, and be on a stable, optimized heart failure regimen for 30 days.

Dr. Greenberg and his associates randomized 39 patients to one of three doses of MYDICAR or to placebo, and all were treated via single intracoronary infusion. All patients were observed for 12 months, with a primary analysis after 6 months of therapy.

The mean age of patients was 61 years, 87% were male, 87% were white, half had heart failure resulting from ischemic cardiomyopathy, and all had NYHA class III heart failure.

Safety measurements included physical examination, electrocardiogram, adverse events, complete blood count, serum chemistries, urinalysis, creatine kinase myocardial band, troponin T, and enzyme-linked immunospot testing for cellular immune response against viral proteins.

Efficacy domains included symptomatic changes in NYHA class and the MLHF (Minnesota Living With Heart Failure) questionnaire; functional changes based on 6-minute walk test and maximal oxygen consumption; changes in N-terminal prohormone brain natriuretic peptide; and evidence of remodeling based on ejection fraction scores and end systolic volume.

CUPID’s primary efficacy end point was defined as evidence of success in one of four areas: group-level analysis, individual analysis, time-to-event analysis, and duration of cardiovascular-related hospitalization analysis. All were deemed statistically significant (P less than .2).

CUPID met the primary efficacy end point for high-dose MYDICAR treatment group vs. placebo in three of the four areas. In the group-level analysis, significant improvements were seen in the treatment group, compared with the placebo group, in improvements in the 6-minute walk test and end systolic volume, with no clinically significant worsening in any end point and numerical superiority to placebo in all other end points.

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group.

In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but this difference did not reach statistical significance.

In the duration of cardiovascular-related hospitalization analysis, the duration of stay was significantly shorter for patients in the treatment group, compared with the placebo group (mean, 2 fewer days).

Dr. Greenberg reported that there were no statistically significant differences between the treatment groups and the placebo groups in the proportion of adverse events or serious events.

“These encouraging results support further studies to determine the value of genetically targeted enzyme replacement of SERCA2a in advanced heart failure,” Dr. Greenberg concluded.

The meeting’s invited discussant, Dr. Michael R. Bristow, president and CEO of ARCA Biopharma Inc., described it as “a big deal to have done gene therapy on this number of patients who are this sick and see absolutely no evidence of safety concern. I believe there’s definite evidence of an efficacy signal ... [and] that CUPID will serve as a catalyst for the development of other gene therapies for heart failure.”

Disclosures: Celladon Corp. funded the trial. Dr. Greenberg said that he had no relevant financial disclosures to make.

SAN DIEGO – In a phase II study of patients with advanced heart failure, gene therapy with MYDICAR was found to be safe and was associated with benefit in clinical outcomes, symptoms, functional status, and cardiac structure.

Deficiency of the protein SERCA2a is central to the progression of heart failure, resulting in abnormal calcium transfer and impairing myocardial relaxation and contraction, Dr. Barry H. Greenberg said at the annual meeting of the Heart Failure Society of America.

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A recombinant adeno-associated viral vector is used to deliver the SERCA2a gene.

The objectives of the phase II study, known as CUPID (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease), were to evaluate safety and feasibility and to explore the activity and efficacy of MYDICAR in patients with advanced heart failure, said Dr. Greenberg, professor of medicine and director of the Advance Heart Failure Treatment Program at the University of California, San Diego.

To be eligible for the trial, patients had to be 18-75 years old, have New York State Heart Association class III or IV heart failure caused by an ischemic or nonischemic etiology, have a maximal oxygen consumption of 20 mL/kg per minute or less, have a left ventricular fraction of 35% or less, and be on a stable, optimized heart failure regimen for 30 days.

Dr. Greenberg and his associates randomized 39 patients to one of three doses of MYDICAR or to placebo, and all were treated via single intracoronary infusion. All patients were observed for 12 months, with a primary analysis after 6 months of therapy.

The mean age of patients was 61 years, 87% were male, 87% were white, half had heart failure resulting from ischemic cardiomyopathy, and all had NYHA class III heart failure.

Safety measurements included physical examination, electrocardiogram, adverse events, complete blood count, serum chemistries, urinalysis, creatine kinase myocardial band, troponin T, and enzyme-linked immunospot testing for cellular immune response against viral proteins.

Efficacy domains included symptomatic changes in NYHA class and the MLHF (Minnesota Living With Heart Failure) questionnaire; functional changes based on 6-minute walk test and maximal oxygen consumption; changes in N-terminal prohormone brain natriuretic peptide; and evidence of remodeling based on ejection fraction scores and end systolic volume.

CUPID’s primary efficacy end point was defined as evidence of success in one of four areas: group-level analysis, individual analysis, time-to-event analysis, and duration of cardiovascular-related hospitalization analysis. All were deemed statistically significant (P less than .2).

CUPID met the primary efficacy end point for high-dose MYDICAR treatment group vs. placebo in three of the four areas. In the group-level analysis, significant improvements were seen in the treatment group, compared with the placebo group, in improvements in the 6-minute walk test and end systolic volume, with no clinically significant worsening in any end point and numerical superiority to placebo in all other end points.

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group.

In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but this difference did not reach statistical significance.

In the duration of cardiovascular-related hospitalization analysis, the duration of stay was significantly shorter for patients in the treatment group, compared with the placebo group (mean, 2 fewer days).

Dr. Greenberg reported that there were no statistically significant differences between the treatment groups and the placebo groups in the proportion of adverse events or serious events.

“These encouraging results support further studies to determine the value of genetically targeted enzyme replacement of SERCA2a in advanced heart failure,” Dr. Greenberg concluded.

The meeting’s invited discussant, Dr. Michael R. Bristow, president and CEO of ARCA Biopharma Inc., described it as “a big deal to have done gene therapy on this number of patients who are this sick and see absolutely no evidence of safety concern. I believe there’s definite evidence of an efficacy signal ... [and] that CUPID will serve as a catalyst for the development of other gene therapies for heart failure.”

Disclosures: Celladon Corp. funded the trial. Dr. Greenberg said that he had no relevant financial disclosures to make.

SAN DIEGO – In a phase II study of patients with advanced heart failure, gene therapy with MYDICAR was found to be safe and was associated with benefit in clinical outcomes, symptoms, functional status, and cardiac structure.

Deficiency of the protein SERCA2a is central to the progression of heart failure, resulting in abnormal calcium transfer and impairing myocardial relaxation and contraction, Dr. Barry H. Greenberg said at the annual meeting of the Heart Failure Society of America.

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A recombinant adeno-associated viral vector is used to deliver the SERCA2a gene.

The objectives of the phase II study, known as CUPID (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease), were to evaluate safety and feasibility and to explore the activity and efficacy of MYDICAR in patients with advanced heart failure, said Dr. Greenberg, professor of medicine and director of the Advance Heart Failure Treatment Program at the University of California, San Diego.

To be eligible for the trial, patients had to be 18-75 years old, have New York State Heart Association class III or IV heart failure caused by an ischemic or nonischemic etiology, have a maximal oxygen consumption of 20 mL/kg per minute or less, have a left ventricular fraction of 35% or less, and be on a stable, optimized heart failure regimen for 30 days.

Dr. Greenberg and his associates randomized 39 patients to one of three doses of MYDICAR or to placebo, and all were treated via single intracoronary infusion. All patients were observed for 12 months, with a primary analysis after 6 months of therapy.

The mean age of patients was 61 years, 87% were male, 87% were white, half had heart failure resulting from ischemic cardiomyopathy, and all had NYHA class III heart failure.

Safety measurements included physical examination, electrocardiogram, adverse events, complete blood count, serum chemistries, urinalysis, creatine kinase myocardial band, troponin T, and enzyme-linked immunospot testing for cellular immune response against viral proteins.

Efficacy domains included symptomatic changes in NYHA class and the MLHF (Minnesota Living With Heart Failure) questionnaire; functional changes based on 6-minute walk test and maximal oxygen consumption; changes in N-terminal prohormone brain natriuretic peptide; and evidence of remodeling based on ejection fraction scores and end systolic volume.

CUPID’s primary efficacy end point was defined as evidence of success in one of four areas: group-level analysis, individual analysis, time-to-event analysis, and duration of cardiovascular-related hospitalization analysis. All were deemed statistically significant (P less than .2).

CUPID met the primary efficacy end point for high-dose MYDICAR treatment group vs. placebo in three of the four areas. In the group-level analysis, significant improvements were seen in the treatment group, compared with the placebo group, in improvements in the 6-minute walk test and end systolic volume, with no clinically significant worsening in any end point and numerical superiority to placebo in all other end points.

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group.

In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but this difference did not reach statistical significance.

In the duration of cardiovascular-related hospitalization analysis, the duration of stay was significantly shorter for patients in the treatment group, compared with the placebo group (mean, 2 fewer days).

Dr. Greenberg reported that there were no statistically significant differences between the treatment groups and the placebo groups in the proportion of adverse events or serious events.

“These encouraging results support further studies to determine the value of genetically targeted enzyme replacement of SERCA2a in advanced heart failure,” Dr. Greenberg concluded.

The meeting’s invited discussant, Dr. Michael R. Bristow, president and CEO of ARCA Biopharma Inc., described it as “a big deal to have done gene therapy on this number of patients who are this sick and see absolutely no evidence of safety concern. I believe there’s definite evidence of an efficacy signal ... [and] that CUPID will serve as a catalyst for the development of other gene therapies for heart failure.”

Disclosures: Celladon Corp. funded the trial. Dr. Greenberg said that he had no relevant financial disclosures to make.

SAN DIEGO – In a phase II study of patients with advanced heart failure, gene therapy with MYDICAR was found to be safe and was associated with benefit in clinical outcomes, symptoms, functional status, and cardiac structure.

Deficiency of the protein SERCA2a is central to the progression of heart failure, resulting in abnormal calcium transfer and impairing myocardial relaxation and contraction, Dr. Barry H. Greenberg said at the annual meeting of the Heart Failure Society of America.

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A recombinant adeno-associated viral vector is used to deliver the SERCA2a gene.

The objectives of the phase II study, known as CUPID (Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease), were to evaluate safety and feasibility and to explore the activity and efficacy of MYDICAR in patients with advanced heart failure, said Dr. Greenberg, professor of medicine and director of the Advance Heart Failure Treatment Program at the University of California, San Diego.

To be eligible for the trial, patients had to be 18-75 years old, have New York State Heart Association class III or IV heart failure caused by an ischemic or nonischemic etiology, have a maximal oxygen consumption of 20 mL/kg per minute or less, have a left ventricular fraction of 35% or less, and be on a stable, optimized heart failure regimen for 30 days.

Dr. Greenberg and his associates randomized 39 patients to one of three doses of MYDICAR or to placebo, and all were treated via single intracoronary infusion. All patients were observed for 12 months, with a primary analysis after 6 months of therapy.

The mean age of patients was 61 years, 87% were male, 87% were white, half had heart failure resulting from ischemic cardiomyopathy, and all had NYHA class III heart failure.

Safety measurements included physical examination, electrocardiogram, adverse events, complete blood count, serum chemistries, urinalysis, creatine kinase myocardial band, troponin T, and enzyme-linked immunospot testing for cellular immune response against viral proteins.

Efficacy domains included symptomatic changes in NYHA class and the MLHF (Minnesota Living With Heart Failure) questionnaire; functional changes based on 6-minute walk test and maximal oxygen consumption; changes in N-terminal prohormone brain natriuretic peptide; and evidence of remodeling based on ejection fraction scores and end systolic volume.

CUPID’s primary efficacy end point was defined as evidence of success in one of four areas: group-level analysis, individual analysis, time-to-event analysis, and duration of cardiovascular-related hospitalization analysis. All were deemed statistically significant (P less than .2).

CUPID met the primary efficacy end point for high-dose MYDICAR treatment group vs. placebo in three of the four areas. In the group-level analysis, significant improvements were seen in the treatment group, compared with the placebo group, in improvements in the 6-minute walk test and end systolic volume, with no clinically significant worsening in any end point and numerical superiority to placebo in all other end points.

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group.

In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but this difference did not reach statistical significance.

In the duration of cardiovascular-related hospitalization analysis, the duration of stay was significantly shorter for patients in the treatment group, compared with the placebo group (mean, 2 fewer days).

Dr. Greenberg reported that there were no statistically significant differences between the treatment groups and the placebo groups in the proportion of adverse events or serious events.

“These encouraging results support further studies to determine the value of genetically targeted enzyme replacement of SERCA2a in advanced heart failure,” Dr. Greenberg concluded.

The meeting’s invited discussant, Dr. Michael R. Bristow, president and CEO of ARCA Biopharma Inc., described it as “a big deal to have done gene therapy on this number of patients who are this sick and see absolutely no evidence of safety concern. I believe there’s definite evidence of an efficacy signal ... [and] that CUPID will serve as a catalyst for the development of other gene therapies for heart failure.”

Disclosures: Celladon Corp. funded the trial. Dr. Greenberg said that he had no relevant financial disclosures to make.

Major Finding: Elderly men experienced a 29% increased risk of coronary heart disease per standard deviation increase in total testosterone and a 22% increased risk per standard deviation increase in bioavailable and free testosterone.

Data Source: Analysis of the National Institutes of Health–funded Osteoporosis Fractures in Men Study (MrOS) ancillary sleep study involving 697 men.

Disclosures: Dr. Sueoka has received funding from the UCSF Clinical and Translational Science Institute.

SAN DIEGO — Elevated endogenous testosterone levels in elderly men are associated with a significantly increased risk of coronary heart disease, according to a large, multicenter study.

“These results are important given that testosterone has been associated with cardiovascular health, and we have yet to understand how it works and to what extent,” Dr. Kristen T. Sueoka said at the meeting.”

“For a disease like coronary heart disease that affects many Americans, any insight into its pathogenesis and any new identifiable and possibly modifiable risk factors can have implications for the health of our population.”

Dr. Sueoka, an internal medicine resident at the University of California, San Francisco, went on to note that while the current study focused on endogenous sex hormones, “our results may raise concern about the safety of exogenous hormone use. Indeed, our results emphasize the importance of further studies.”

She and her associates analyzed data from 697 men enrolled in the National Institutes of Health–funded Osteoporosis Fractures in Men Study (MrOS) ancillary sleep study, which targeted elderly men at six medical centers in the United States and followed them for an average of 4 years.

At baseline, the men underwent sleep studies and had hormones processed by mass spectrometry for sex hormones and chemiluminescence for sex hormone–binding globulin (SHBG). They also filled out survey information and answered personal interviews regarding their extensive medical history, including risk factors for coronary heart disease.

Study participants were contacted every 4 months by mail to monitor for coronary heart disease events: acute coronary syndrome, revascularization (including percutaneous coronary intervention and coronary artery bypass graft surgery), ischemic heart failure, and ischemia-related mortality. Reported events were reviewed by a cardiologist.

The researchers then analyzed the relationship between coronary heart disease risk and quartile of sex hormones. For example, the quartiles of total testosterone were less than 308 ng/dL, 308–392 ng/dL, 393–495 ng/dL, and greater than 495 ng/dL.

At baseline, the mean age of the study participants was 72 years and their mean body mass index was 28 kg/m

Dr. Sueoka reported that at 4 years, 100 of the men (14%) suffered an incident coronary heart disease event. The researchers observed a 29% increased risk of coronary heart disease per standard deviation increase in total serum testosterone.

The pattern was similar for bioavailable and free testosterone (a 22% increased risk of coronary heart disease per standard deviation increase in each hormone).

Higher levels of SHBG also were associated with increased risk of heart disease (a 31% increase per standard deviation increase). However, no significant associations between total estradiol and coronary heart disease risk were observed.

In the analysis of sex hormones by quartile, the researchers observed “an increasing risk of coronary heart disease as you move from the lowest to highest quartiles of testosterone, which was statistically significant,” Dr. Sueoka said.

“We did not find a statistically significant relationship between total estradiol and coronary heart disease.”

“On the other hand, there was a statistically significant relationship looking at SHBG, with increasing of SHBG associated with a higher risk of coronary heart disease,” Dr. Sueoka said.

The study was limited by the fact that it included an older population and that there was only one measurement of sex hormone, she said.

“Higher endogenous testosterone was associated with an increased risk for coronary heart disease,” Dr. Sueoka concluded.

“This effect remained after accounting for common cardiovascular risk factors. We noted similar trends for all forms of testosterone, including bioavailable and free. We did further analyses which showed a similar trend for broader cardiovascular disease, including stroke and peripheral vascular disease,” she added.

Risk of coronary heart disease increased from the lowest to highest quartiles of testosterone.

Source DR. SUEOKA

Major Finding: Elderly men experienced a 29% increased risk of coronary heart disease per standard deviation increase in total testosterone and a 22% increased risk per standard deviation increase in bioavailable and free testosterone.

Data Source: Analysis of the National Institutes of Health–funded Osteoporosis Fractures in Men Study (MrOS) ancillary sleep study involving 697 men.

Disclosures: Dr. Sueoka has received funding from the UCSF Clinical and Translational Science Institute.

SAN DIEGO — Elevated endogenous testosterone levels in elderly men are associated with a significantly increased risk of coronary heart disease, according to a large, multicenter study.

“These results are important given that testosterone has been associated with cardiovascular health, and we have yet to understand how it works and to what extent,” Dr. Kristen T. Sueoka said at the meeting.”

“For a disease like coronary heart disease that affects many Americans, any insight into its pathogenesis and any new identifiable and possibly modifiable risk factors can have implications for the health of our population.”

Dr. Sueoka, an internal medicine resident at the University of California, San Francisco, went on to note that while the current study focused on endogenous sex hormones, “our results may raise concern about the safety of exogenous hormone use. Indeed, our results emphasize the importance of further studies.”

She and her associates analyzed data from 697 men enrolled in the National Institutes of Health–funded Osteoporosis Fractures in Men Study (MrOS) ancillary sleep study, which targeted elderly men at six medical centers in the United States and followed them for an average of 4 years.

At baseline, the men underwent sleep studies and had hormones processed by mass spectrometry for sex hormones and chemiluminescence for sex hormone–binding globulin (SHBG). They also filled out survey information and answered personal interviews regarding their extensive medical history, including risk factors for coronary heart disease.

Study participants were contacted every 4 months by mail to monitor for coronary heart disease events: acute coronary syndrome, revascularization (including percutaneous coronary intervention and coronary artery bypass graft surgery), ischemic heart failure, and ischemia-related mortality. Reported events were reviewed by a cardiologist.

The researchers then analyzed the relationship between coronary heart disease risk and quartile of sex hormones. For example, the quartiles of total testosterone were less than 308 ng/dL, 308–392 ng/dL, 393–495 ng/dL, and greater than 495 ng/dL.

At baseline, the mean age of the study participants was 72 years and their mean body mass index was 28 kg/m

Dr. Sueoka reported that at 4 years, 100 of the men (14%) suffered an incident coronary heart disease event. The researchers observed a 29% increased risk of coronary heart disease per standard deviation increase in total serum testosterone.

The pattern was similar for bioavailable and free testosterone (a 22% increased risk of coronary heart disease per standard deviation increase in each hormone).

Higher levels of SHBG also were associated with increased risk of heart disease (a 31% increase per standard deviation increase). However, no significant associations between total estradiol and coronary heart disease risk were observed.

In the analysis of sex hormones by quartile, the researchers observed “an increasing risk of coronary heart disease as you move from the lowest to highest quartiles of testosterone, which was statistically significant,” Dr. Sueoka said.

“We did not find a statistically significant relationship between total estradiol and coronary heart disease.”

“On the other hand, there was a statistically significant relationship looking at SHBG, with increasing of SHBG associated with a higher risk of coronary heart disease,” Dr. Sueoka said.

The study was limited by the fact that it included an older population and that there was only one measurement of sex hormone, she said.

“Higher endogenous testosterone was associated with an increased risk for coronary heart disease,” Dr. Sueoka concluded.

“This effect remained after accounting for common cardiovascular risk factors. We noted similar trends for all forms of testosterone, including bioavailable and free. We did further analyses which showed a similar trend for broader cardiovascular disease, including stroke and peripheral vascular disease,” she added.

Risk of coronary heart disease increased from the lowest to highest quartiles of testosterone.

Source DR. SUEOKA

Major Finding: Elderly men experienced a 29% increased risk of coronary heart disease per standard deviation increase in total testosterone and a 22% increased risk per standard deviation increase in bioavailable and free testosterone.

Data Source: Analysis of the National Institutes of Health–funded Osteoporosis Fractures in Men Study (MrOS) ancillary sleep study involving 697 men.

Disclosures: Dr. Sueoka has received funding from the UCSF Clinical and Translational Science Institute.

SAN DIEGO — Elevated endogenous testosterone levels in elderly men are associated with a significantly increased risk of coronary heart disease, according to a large, multicenter study.

“These results are important given that testosterone has been associated with cardiovascular health, and we have yet to understand how it works and to what extent,” Dr. Kristen T. Sueoka said at the meeting.”

“For a disease like coronary heart disease that affects many Americans, any insight into its pathogenesis and any new identifiable and possibly modifiable risk factors can have implications for the health of our population.”

Dr. Sueoka, an internal medicine resident at the University of California, San Francisco, went on to note that while the current study focused on endogenous sex hormones, “our results may raise concern about the safety of exogenous hormone use. Indeed, our results emphasize the importance of further studies.”

She and her associates analyzed data from 697 men enrolled in the National Institutes of Health–funded Osteoporosis Fractures in Men Study (MrOS) ancillary sleep study, which targeted elderly men at six medical centers in the United States and followed them for an average of 4 years.

At baseline, the men underwent sleep studies and had hormones processed by mass spectrometry for sex hormones and chemiluminescence for sex hormone–binding globulin (SHBG). They also filled out survey information and answered personal interviews regarding their extensive medical history, including risk factors for coronary heart disease.

Study participants were contacted every 4 months by mail to monitor for coronary heart disease events: acute coronary syndrome, revascularization (including percutaneous coronary intervention and coronary artery bypass graft surgery), ischemic heart failure, and ischemia-related mortality. Reported events were reviewed by a cardiologist.

The researchers then analyzed the relationship between coronary heart disease risk and quartile of sex hormones. For example, the quartiles of total testosterone were less than 308 ng/dL, 308–392 ng/dL, 393–495 ng/dL, and greater than 495 ng/dL.

At baseline, the mean age of the study participants was 72 years and their mean body mass index was 28 kg/m

Dr. Sueoka reported that at 4 years, 100 of the men (14%) suffered an incident coronary heart disease event. The researchers observed a 29% increased risk of coronary heart disease per standard deviation increase in total serum testosterone.

The pattern was similar for bioavailable and free testosterone (a 22% increased risk of coronary heart disease per standard deviation increase in each hormone).

Higher levels of SHBG also were associated with increased risk of heart disease (a 31% increase per standard deviation increase). However, no significant associations between total estradiol and coronary heart disease risk were observed.

In the analysis of sex hormones by quartile, the researchers observed “an increasing risk of coronary heart disease as you move from the lowest to highest quartiles of testosterone, which was statistically significant,” Dr. Sueoka said.

“We did not find a statistically significant relationship between total estradiol and coronary heart disease.”

“On the other hand, there was a statistically significant relationship looking at SHBG, with increasing of SHBG associated with a higher risk of coronary heart disease,” Dr. Sueoka said.

The study was limited by the fact that it included an older population and that there was only one measurement of sex hormone, she said.

“Higher endogenous testosterone was associated with an increased risk for coronary heart disease,” Dr. Sueoka concluded.

“This effect remained after accounting for common cardiovascular risk factors. We noted similar trends for all forms of testosterone, including bioavailable and free. We did further analyses which showed a similar trend for broader cardiovascular disease, including stroke and peripheral vascular disease,” she added.

Risk of coronary heart disease increased from the lowest to highest quartiles of testosterone.

Source DR. SUEOKA