Mitchel L. Zoler, PhD

PHILADELPHIA — Treatment with an investigational, oral, immune-modulating drug led to significant improvement in patients with active rheumatoid arthritis refractory to methotrexate in a phase II study in more than 400 patients.

“These results confirm our earlier observations of the effect of this drug on a background of methotrexate,” Dr. Michael E. Weinblatt said at the annual meeting of the American College of Rheumatology.

The two tested dosages of R788 (fostamatinib disodium), 150 mg once daily and 100 mg b.i.d., each led to significantly higher rates of ACR20 responses compared with placebo, the study's primary end point, said Dr. Weinblatt, a professor of medicine at Harvard University and codirector of clinical rheumatology at Brigham and Women's Hospital in Boston.

However, the story may be different in patients with active RA who have failed a biologic. In a second phase II study with the same agent in 219 such patients, administration of R788 at 100 mg b.i.d. did not produce an ACR20 response that was significantly better than placebo, reported Dr. Mark C. Genovese, a professor of medicine/immunology and rheumatology at Stanford (Calif.) University. He noted that this negative, second study seemed potentially flawed because its placebo group had an “exceptionally high placebo response rate.”

R788 is a selective inhibitor of Syk kinase, an important immuno-regulating enzyme that affects mast cells, macrophages, neutrophils, and B cells. Prior studies showed that Syk kinase was present in the synovial fluid of RA patients.

The trial enrolled patients with active RA and at least 6 (out of 28) painful and swollen joints and either a C-reactive protein level above the upper limit of normal or an erythrocyte sedimentation rate greater than 28 mm/hr. Patients also had to be on a methotrexate regimen of at least 10 mg/week for at least 3 months and with a stable dosage for at least 6 weeks. Patients could also be on stable dosages of low-dose prednisone and/or NSAIDs, but other disease modifying antirheumatic drugs, including any biologic, had to be washed out. Their average age was 53 years, about 85% were women, and their mean disease duration was 9 years. Each patient had an average of 12 painful and swollen joints.

After 6 months, an ACR20 response rate occurred in 66% of 152 patients randomized to 100 mg b.i.d., in 57% of 152 patients randomized to 150 mg once daily, and in 35% of 153 placebo patients, analyzed on an intention-to-treat basis. The differences between each of the two active arms and the placebo group were statistically significant. The 100 mg b.i.d. patients also had significantly better improvements in their ACR50 and ACR70 responses compared with placebo, as well as a significantly better rate of patients with a disease activity score (DAS)-28 of less than 2.6. Patients on 150 mg once daily also fared significantly better than the placebo group for the ACR50 and DAS-28 responses, but their ACR70 response did not significant surpass the placebo group.

The incidence of serious adverse events was similar in all three groups, with 7 in the placebo arm, 5 in patients getting 150 mg daily, and 13 in those getting 100 mg b.i.d. No patient died or had an opportunistic infection. The most common adverse event on treatment was diarrhea in 3% of placebo patients, in 12% of patients on 150 mg once daily, and in 19% of patients getting 100 mg b.i.d.

Patients receiving R788 also showed small increases in the rates of neutropenia and in elevations of liver enzymes, compared with the placebo patients. The rate of patients who had a reduction in their dosage because of an adverse event was 14% in each of the R788 arms and 4% in placebo patients. Discontinuations were for blood pressure elevations, liver enzyme elevations greater than three times the upper limit of normal, neutropenia, or gastrointestinal events.

The second study included 219 patients with active RA who previously failed to respond to or tolerate a biologic treatment. Their average age was 56 years, 80% were women, and their average disease duration was 12 years. After 3 months of treatment, the 146 patients getting 100 mg R788 b.i.d. did not have a significantly better response than 73 placebo patients for any ACR response or DAS28 measure. The patients on R788 did have significantly greater reductions in their level of C reactive protein and in their erythrocyte sedimentation rate than those on placebo.

One serious adverse event, an infection, occurred in the placebo patients. Patients on R788 had 13 serious adverse events, including 3 infections, none of them opportunistic. In the placebo group, 3% of patients had to lower their dose due to adverse events as did 14% of those on the active drug.

Disclosures: Rigel Pharmaceuticals, the company developing R788, sponsored both studies. Dr. Weinblatt and Dr. Genovese served as consultants to Rigel, and two of their associates on the study are full-time employees of the company.

R788 led to significantly higher rates of ACR20 responses, compared with placebo.

Source DR. WEINBLATT

PHILADELPHIA — Treatment with an investigational, oral, immune-modulating drug led to significant improvement in patients with active rheumatoid arthritis refractory to methotrexate in a phase II study in more than 400 patients.

“These results confirm our earlier observations of the effect of this drug on a background of methotrexate,” Dr. Michael E. Weinblatt said at the annual meeting of the American College of Rheumatology.

The two tested dosages of R788 (fostamatinib disodium), 150 mg once daily and 100 mg b.i.d., each led to significantly higher rates of ACR20 responses compared with placebo, the study's primary end point, said Dr. Weinblatt, a professor of medicine at Harvard University and codirector of clinical rheumatology at Brigham and Women's Hospital in Boston.

However, the story may be different in patients with active RA who have failed a biologic. In a second phase II study with the same agent in 219 such patients, administration of R788 at 100 mg b.i.d. did not produce an ACR20 response that was significantly better than placebo, reported Dr. Mark C. Genovese, a professor of medicine/immunology and rheumatology at Stanford (Calif.) University. He noted that this negative, second study seemed potentially flawed because its placebo group had an “exceptionally high placebo response rate.”

R788 is a selective inhibitor of Syk kinase, an important immuno-regulating enzyme that affects mast cells, macrophages, neutrophils, and B cells. Prior studies showed that Syk kinase was present in the synovial fluid of RA patients.

The trial enrolled patients with active RA and at least 6 (out of 28) painful and swollen joints and either a C-reactive protein level above the upper limit of normal or an erythrocyte sedimentation rate greater than 28 mm/hr. Patients also had to be on a methotrexate regimen of at least 10 mg/week for at least 3 months and with a stable dosage for at least 6 weeks. Patients could also be on stable dosages of low-dose prednisone and/or NSAIDs, but other disease modifying antirheumatic drugs, including any biologic, had to be washed out. Their average age was 53 years, about 85% were women, and their mean disease duration was 9 years. Each patient had an average of 12 painful and swollen joints.

After 6 months, an ACR20 response rate occurred in 66% of 152 patients randomized to 100 mg b.i.d., in 57% of 152 patients randomized to 150 mg once daily, and in 35% of 153 placebo patients, analyzed on an intention-to-treat basis. The differences between each of the two active arms and the placebo group were statistically significant. The 100 mg b.i.d. patients also had significantly better improvements in their ACR50 and ACR70 responses compared with placebo, as well as a significantly better rate of patients with a disease activity score (DAS)-28 of less than 2.6. Patients on 150 mg once daily also fared significantly better than the placebo group for the ACR50 and DAS-28 responses, but their ACR70 response did not significant surpass the placebo group.

The incidence of serious adverse events was similar in all three groups, with 7 in the placebo arm, 5 in patients getting 150 mg daily, and 13 in those getting 100 mg b.i.d. No patient died or had an opportunistic infection. The most common adverse event on treatment was diarrhea in 3% of placebo patients, in 12% of patients on 150 mg once daily, and in 19% of patients getting 100 mg b.i.d.

Patients receiving R788 also showed small increases in the rates of neutropenia and in elevations of liver enzymes, compared with the placebo patients. The rate of patients who had a reduction in their dosage because of an adverse event was 14% in each of the R788 arms and 4% in placebo patients. Discontinuations were for blood pressure elevations, liver enzyme elevations greater than three times the upper limit of normal, neutropenia, or gastrointestinal events.

The second study included 219 patients with active RA who previously failed to respond to or tolerate a biologic treatment. Their average age was 56 years, 80% were women, and their average disease duration was 12 years. After 3 months of treatment, the 146 patients getting 100 mg R788 b.i.d. did not have a significantly better response than 73 placebo patients for any ACR response or DAS28 measure. The patients on R788 did have significantly greater reductions in their level of C reactive protein and in their erythrocyte sedimentation rate than those on placebo.

One serious adverse event, an infection, occurred in the placebo patients. Patients on R788 had 13 serious adverse events, including 3 infections, none of them opportunistic. In the placebo group, 3% of patients had to lower their dose due to adverse events as did 14% of those on the active drug.

Disclosures: Rigel Pharmaceuticals, the company developing R788, sponsored both studies. Dr. Weinblatt and Dr. Genovese served as consultants to Rigel, and two of their associates on the study are full-time employees of the company.

R788 led to significantly higher rates of ACR20 responses, compared with placebo.

Source DR. WEINBLATT

PHILADELPHIA — Treatment with an investigational, oral, immune-modulating drug led to significant improvement in patients with active rheumatoid arthritis refractory to methotrexate in a phase II study in more than 400 patients.

“These results confirm our earlier observations of the effect of this drug on a background of methotrexate,” Dr. Michael E. Weinblatt said at the annual meeting of the American College of Rheumatology.

The two tested dosages of R788 (fostamatinib disodium), 150 mg once daily and 100 mg b.i.d., each led to significantly higher rates of ACR20 responses compared with placebo, the study's primary end point, said Dr. Weinblatt, a professor of medicine at Harvard University and codirector of clinical rheumatology at Brigham and Women's Hospital in Boston.

However, the story may be different in patients with active RA who have failed a biologic. In a second phase II study with the same agent in 219 such patients, administration of R788 at 100 mg b.i.d. did not produce an ACR20 response that was significantly better than placebo, reported Dr. Mark C. Genovese, a professor of medicine/immunology and rheumatology at Stanford (Calif.) University. He noted that this negative, second study seemed potentially flawed because its placebo group had an “exceptionally high placebo response rate.”

R788 is a selective inhibitor of Syk kinase, an important immuno-regulating enzyme that affects mast cells, macrophages, neutrophils, and B cells. Prior studies showed that Syk kinase was present in the synovial fluid of RA patients.

The trial enrolled patients with active RA and at least 6 (out of 28) painful and swollen joints and either a C-reactive protein level above the upper limit of normal or an erythrocyte sedimentation rate greater than 28 mm/hr. Patients also had to be on a methotrexate regimen of at least 10 mg/week for at least 3 months and with a stable dosage for at least 6 weeks. Patients could also be on stable dosages of low-dose prednisone and/or NSAIDs, but other disease modifying antirheumatic drugs, including any biologic, had to be washed out. Their average age was 53 years, about 85% were women, and their mean disease duration was 9 years. Each patient had an average of 12 painful and swollen joints.

After 6 months, an ACR20 response rate occurred in 66% of 152 patients randomized to 100 mg b.i.d., in 57% of 152 patients randomized to 150 mg once daily, and in 35% of 153 placebo patients, analyzed on an intention-to-treat basis. The differences between each of the two active arms and the placebo group were statistically significant. The 100 mg b.i.d. patients also had significantly better improvements in their ACR50 and ACR70 responses compared with placebo, as well as a significantly better rate of patients with a disease activity score (DAS)-28 of less than 2.6. Patients on 150 mg once daily also fared significantly better than the placebo group for the ACR50 and DAS-28 responses, but their ACR70 response did not significant surpass the placebo group.

The incidence of serious adverse events was similar in all three groups, with 7 in the placebo arm, 5 in patients getting 150 mg daily, and 13 in those getting 100 mg b.i.d. No patient died or had an opportunistic infection. The most common adverse event on treatment was diarrhea in 3% of placebo patients, in 12% of patients on 150 mg once daily, and in 19% of patients getting 100 mg b.i.d.

Patients receiving R788 also showed small increases in the rates of neutropenia and in elevations of liver enzymes, compared with the placebo patients. The rate of patients who had a reduction in their dosage because of an adverse event was 14% in each of the R788 arms and 4% in placebo patients. Discontinuations were for blood pressure elevations, liver enzyme elevations greater than three times the upper limit of normal, neutropenia, or gastrointestinal events.

The second study included 219 patients with active RA who previously failed to respond to or tolerate a biologic treatment. Their average age was 56 years, 80% were women, and their average disease duration was 12 years. After 3 months of treatment, the 146 patients getting 100 mg R788 b.i.d. did not have a significantly better response than 73 placebo patients for any ACR response or DAS28 measure. The patients on R788 did have significantly greater reductions in their level of C reactive protein and in their erythrocyte sedimentation rate than those on placebo.

One serious adverse event, an infection, occurred in the placebo patients. Patients on R788 had 13 serious adverse events, including 3 infections, none of them opportunistic. In the placebo group, 3% of patients had to lower their dose due to adverse events as did 14% of those on the active drug.

Disclosures: Rigel Pharmaceuticals, the company developing R788, sponsored both studies. Dr. Weinblatt and Dr. Genovese served as consultants to Rigel, and two of their associates on the study are full-time employees of the company.

R788 led to significantly higher rates of ACR20 responses, compared with placebo.

Source DR. WEINBLATT

PHILADELPHIA — Women's risk factors for developing gout are similar to those in men, and baseline serum levels of uric acid may be the most powerful predictor, findings from the Framingham Heart Study show.

Women with no clinical indication of gout but a serum uric acid level of 8.0 mg/dL or greater at baseline had a subsequent 2.7% rate of gout during an average 28 years of follow-up—a 46-fold higher rate than women with a serum uric acid level of less than 5 mg/dL at baseline, Dr. Vidula Bhole said at the annual meeting of the American College of Rheumatology.

Serum uric acid likewise posed a powerful risk in men. Those with a level of 8 mg/dL or more at baseline had a 3.3% incidence rate during follow-up, 61-fold higher than men who entered the study with a serum level below 5.0 mg/dL.

Even a baseline uric acid level of 5-5.9 mg/dL conferred a greater than threefold higher risk for developing gout in women and a greater than fourfold higher risk in men, compared with those whose level was under 5 mg/dL, said Dr. Bhole, an epidemiologist in the Arthritis Research Centre of Canada at the University of British Columbia in Vancouver. (See table.)

Dr. Bhole and her associates used prospectively collected data from the more than 5,000 residents of Framingham, Mass., who entered the Heart Study in 1948, at a baseline age of 29-62 years. Among the enrollees, 4,427 had no history of gout at entry and formed the focus for the new analysis.

The group included 2,476 women, with an average age of 47 years and an average serum uric acid level of 4.0 mg/dL. The group also included 1,967 men who entered at an average age of 46 years and a mean serum uric acid level of 5.1 mg/dL.

Average body mass index was 25 kg/m

The subjects developed 304 cases of gout during an average 28 years of follow-up, with an incidence rate of 1.4 cases/1,000 person-years of follow-up in the women and 4.0 cases/1,000 person years follow-up in the men.

An analysis of gout incidence rates relative to baseline serum uric acid showed that, for any baseline level, women developed less gout than men. For example, among people who entered the study with a serum level of 7.0-7.9 mg/dL, the subsequent incidence was 1.3% in women and 1.8% in men.

A multivariate analysis identified several baseline factors linked to a significantly higher rate of incident gout in both genders: age, obesity, heavy alcohol use, hypertension, and diuretic use.

Dr. Bhole said she had no relevant financial relationships. Two of her study colleagues received grant support from and served as consultants to Takeda. One of Dr. Bhole's associates also serves on the advisory board for Savient, a company developing a uric acid–lowering drug.

Age, obesity, and heavy alcohol and diuretic use were linked to a higher rate of incident gout in both genders.

Source DR. BHOLE

Elsevier Global Medical News

PHILADELPHIA — Women's risk factors for developing gout are similar to those in men, and baseline serum levels of uric acid may be the most powerful predictor, findings from the Framingham Heart Study show.

Women with no clinical indication of gout but a serum uric acid level of 8.0 mg/dL or greater at baseline had a subsequent 2.7% rate of gout during an average 28 years of follow-up—a 46-fold higher rate than women with a serum uric acid level of less than 5 mg/dL at baseline, Dr. Vidula Bhole said at the annual meeting of the American College of Rheumatology.

Serum uric acid likewise posed a powerful risk in men. Those with a level of 8 mg/dL or more at baseline had a 3.3% incidence rate during follow-up, 61-fold higher than men who entered the study with a serum level below 5.0 mg/dL.

Even a baseline uric acid level of 5-5.9 mg/dL conferred a greater than threefold higher risk for developing gout in women and a greater than fourfold higher risk in men, compared with those whose level was under 5 mg/dL, said Dr. Bhole, an epidemiologist in the Arthritis Research Centre of Canada at the University of British Columbia in Vancouver. (See table.)

Dr. Bhole and her associates used prospectively collected data from the more than 5,000 residents of Framingham, Mass., who entered the Heart Study in 1948, at a baseline age of 29-62 years. Among the enrollees, 4,427 had no history of gout at entry and formed the focus for the new analysis.

The group included 2,476 women, with an average age of 47 years and an average serum uric acid level of 4.0 mg/dL. The group also included 1,967 men who entered at an average age of 46 years and a mean serum uric acid level of 5.1 mg/dL.

Average body mass index was 25 kg/m

The subjects developed 304 cases of gout during an average 28 years of follow-up, with an incidence rate of 1.4 cases/1,000 person-years of follow-up in the women and 4.0 cases/1,000 person years follow-up in the men.

An analysis of gout incidence rates relative to baseline serum uric acid showed that, for any baseline level, women developed less gout than men. For example, among people who entered the study with a serum level of 7.0-7.9 mg/dL, the subsequent incidence was 1.3% in women and 1.8% in men.

A multivariate analysis identified several baseline factors linked to a significantly higher rate of incident gout in both genders: age, obesity, heavy alcohol use, hypertension, and diuretic use.

Dr. Bhole said she had no relevant financial relationships. Two of her study colleagues received grant support from and served as consultants to Takeda. One of Dr. Bhole's associates also serves on the advisory board for Savient, a company developing a uric acid–lowering drug.

Age, obesity, and heavy alcohol and diuretic use were linked to a higher rate of incident gout in both genders.

Source DR. BHOLE

Elsevier Global Medical News

PHILADELPHIA — Women's risk factors for developing gout are similar to those in men, and baseline serum levels of uric acid may be the most powerful predictor, findings from the Framingham Heart Study show.

Women with no clinical indication of gout but a serum uric acid level of 8.0 mg/dL or greater at baseline had a subsequent 2.7% rate of gout during an average 28 years of follow-up—a 46-fold higher rate than women with a serum uric acid level of less than 5 mg/dL at baseline, Dr. Vidula Bhole said at the annual meeting of the American College of Rheumatology.

Serum uric acid likewise posed a powerful risk in men. Those with a level of 8 mg/dL or more at baseline had a 3.3% incidence rate during follow-up, 61-fold higher than men who entered the study with a serum level below 5.0 mg/dL.

Even a baseline uric acid level of 5-5.9 mg/dL conferred a greater than threefold higher risk for developing gout in women and a greater than fourfold higher risk in men, compared with those whose level was under 5 mg/dL, said Dr. Bhole, an epidemiologist in the Arthritis Research Centre of Canada at the University of British Columbia in Vancouver. (See table.)

Dr. Bhole and her associates used prospectively collected data from the more than 5,000 residents of Framingham, Mass., who entered the Heart Study in 1948, at a baseline age of 29-62 years. Among the enrollees, 4,427 had no history of gout at entry and formed the focus for the new analysis.

The group included 2,476 women, with an average age of 47 years and an average serum uric acid level of 4.0 mg/dL. The group also included 1,967 men who entered at an average age of 46 years and a mean serum uric acid level of 5.1 mg/dL.

Average body mass index was 25 kg/m

The subjects developed 304 cases of gout during an average 28 years of follow-up, with an incidence rate of 1.4 cases/1,000 person-years of follow-up in the women and 4.0 cases/1,000 person years follow-up in the men.

An analysis of gout incidence rates relative to baseline serum uric acid showed that, for any baseline level, women developed less gout than men. For example, among people who entered the study with a serum level of 7.0-7.9 mg/dL, the subsequent incidence was 1.3% in women and 1.8% in men.

A multivariate analysis identified several baseline factors linked to a significantly higher rate of incident gout in both genders: age, obesity, heavy alcohol use, hypertension, and diuretic use.

Dr. Bhole said she had no relevant financial relationships. Two of her study colleagues received grant support from and served as consultants to Takeda. One of Dr. Bhole's associates also serves on the advisory board for Savient, a company developing a uric acid–lowering drug.

Age, obesity, and heavy alcohol and diuretic use were linked to a higher rate of incident gout in both genders.

Source DR. BHOLE

Elsevier Global Medical News

ORLANDO — The best shunt to use in the Norwood operation, during the first stage of repairing hypoplastic left heart syndrome, remains a toss-up despite completion of a yearlong randomized trial with more than 500 infants.

“What we see at 12 months is a survival advantage” for a right ventricle-to-pulmonary artery shunt (RVPAS) compared with the alternative, modified Blalock Taussig shunt (MBTS), Dr. Richard G. Ohye said at the annual scientific sessions of the American Heart Association.

“The concern is that the [survival] curves begin to converge, and in the future will they remain parallel or cross?” As a result of this uncertainty about long-term survival, “concrete recommendation will have to wait for further follow-up,” said Dr. Ohye, director of pediatric cardiac surgery at the University of Michigan, Ann Arbor.

The MBTS has been the traditional option during the Norwood operation, but concerns about its safety focused on the retrograde coronary flow it allows that could potentially interfere with coronary perfusion and lead to ischemia and possibly death. The other option, the RVPAS, irequires a ventriculotomy, which could compromise right ventricular function and might also trigger arrhythmias.

Uncertainty over which shunt produced the best outcomes led to the Single Ventricle Reconstruction Trial, done through the Pediatric Heart Network at 15 U.S. sites. It randomized 555 infants scheduled for the Norwood operation to either of the two shunt strategies.

One year after randomization, the incidence of death or need for heart transplant was 26% in patients getting the RVPAS and 36% in those getting the MBTS, a statistically significant 10% absolute difference in the primary end point in favor of the RVPAS. Although this was the primary end point, it did not tell the entire story.

Follow-up continued and after an average of 32 months, 16 additional deaths or heart transplants occurred in the RVPAS group compared with 7 of these events in the MBTS infants, a trend that led to the observation that the event curves may be converging over time.

Another worrisome finding was that unintended cardiac procedures such as balloon dilatations of the shunt or neoaorta, shunt revisions, or unplanned pulmonary artery reconstructions, were significantly more common in the RVPAS infants, 54%, compared with those who received MBTS, 44%. The RVPAS also produced smaller pulmonary arteries by the Nakata index.

By most other criteria, the two procedures produced similar outcomes. Time to extubation during surgery, duration of ventilation, and total days spent in the ICU and in the hospital were identical, as was the percentage of infants who required an open sternum or extracorporeal membrane oxygenation. The incidence of nonfatal serious adverse events was similar in the two arms, as was long-term right ventricular function. Infants treated with a RVPAS had the advantage of a significantly reduced need for cardiopulmonary resuscitation, 13%, compared with 20% in the MBTS infants.

“Although 12-month, transplant-free survival is higher with RVPAS, the emergence of later mortality with RVPAS is of concern. Continued follow-up of the cohort will be important to determine intermediate and long-term outcomes,” Dr. Ohye said.

Vitals

Major Findings: At 1 year, infants who received the RVPAS had a significant1absolute reduction in death or need for transplant vs. those who received the MBTS; after 1 year that rate was higher in the RVPAS patients.

Source of Data: The Single Ventricle Reconstruction Trial, involving 555 infants.

Disclosures: The National Heart, Lung, and Blood Institute sponsored the trial. Dr. Ohye had no conflicts.

ORLANDO — The best shunt to use in the Norwood operation, during the first stage of repairing hypoplastic left heart syndrome, remains a toss-up despite completion of a yearlong randomized trial with more than 500 infants.

“What we see at 12 months is a survival advantage” for a right ventricle-to-pulmonary artery shunt (RVPAS) compared with the alternative, modified Blalock Taussig shunt (MBTS), Dr. Richard G. Ohye said at the annual scientific sessions of the American Heart Association.

“The concern is that the [survival] curves begin to converge, and in the future will they remain parallel or cross?” As a result of this uncertainty about long-term survival, “concrete recommendation will have to wait for further follow-up,” said Dr. Ohye, director of pediatric cardiac surgery at the University of Michigan, Ann Arbor.

The MBTS has been the traditional option during the Norwood operation, but concerns about its safety focused on the retrograde coronary flow it allows that could potentially interfere with coronary perfusion and lead to ischemia and possibly death. The other option, the RVPAS, irequires a ventriculotomy, which could compromise right ventricular function and might also trigger arrhythmias.

Uncertainty over which shunt produced the best outcomes led to the Single Ventricle Reconstruction Trial, done through the Pediatric Heart Network at 15 U.S. sites. It randomized 555 infants scheduled for the Norwood operation to either of the two shunt strategies.

One year after randomization, the incidence of death or need for heart transplant was 26% in patients getting the RVPAS and 36% in those getting the MBTS, a statistically significant 10% absolute difference in the primary end point in favor of the RVPAS. Although this was the primary end point, it did not tell the entire story.

Follow-up continued and after an average of 32 months, 16 additional deaths or heart transplants occurred in the RVPAS group compared with 7 of these events in the MBTS infants, a trend that led to the observation that the event curves may be converging over time.

Another worrisome finding was that unintended cardiac procedures such as balloon dilatations of the shunt or neoaorta, shunt revisions, or unplanned pulmonary artery reconstructions, were significantly more common in the RVPAS infants, 54%, compared with those who received MBTS, 44%. The RVPAS also produced smaller pulmonary arteries by the Nakata index.

By most other criteria, the two procedures produced similar outcomes. Time to extubation during surgery, duration of ventilation, and total days spent in the ICU and in the hospital were identical, as was the percentage of infants who required an open sternum or extracorporeal membrane oxygenation. The incidence of nonfatal serious adverse events was similar in the two arms, as was long-term right ventricular function. Infants treated with a RVPAS had the advantage of a significantly reduced need for cardiopulmonary resuscitation, 13%, compared with 20% in the MBTS infants.

“Although 12-month, transplant-free survival is higher with RVPAS, the emergence of later mortality with RVPAS is of concern. Continued follow-up of the cohort will be important to determine intermediate and long-term outcomes,” Dr. Ohye said.

Vitals

Major Findings: At 1 year, infants who received the RVPAS had a significant1absolute reduction in death or need for transplant vs. those who received the MBTS; after 1 year that rate was higher in the RVPAS patients.

Source of Data: The Single Ventricle Reconstruction Trial, involving 555 infants.

Disclosures: The National Heart, Lung, and Blood Institute sponsored the trial. Dr. Ohye had no conflicts.

ORLANDO — The best shunt to use in the Norwood operation, during the first stage of repairing hypoplastic left heart syndrome, remains a toss-up despite completion of a yearlong randomized trial with more than 500 infants.

“What we see at 12 months is a survival advantage” for a right ventricle-to-pulmonary artery shunt (RVPAS) compared with the alternative, modified Blalock Taussig shunt (MBTS), Dr. Richard G. Ohye said at the annual scientific sessions of the American Heart Association.

“The concern is that the [survival] curves begin to converge, and in the future will they remain parallel or cross?” As a result of this uncertainty about long-term survival, “concrete recommendation will have to wait for further follow-up,” said Dr. Ohye, director of pediatric cardiac surgery at the University of Michigan, Ann Arbor.

The MBTS has been the traditional option during the Norwood operation, but concerns about its safety focused on the retrograde coronary flow it allows that could potentially interfere with coronary perfusion and lead to ischemia and possibly death. The other option, the RVPAS, irequires a ventriculotomy, which could compromise right ventricular function and might also trigger arrhythmias.

Uncertainty over which shunt produced the best outcomes led to the Single Ventricle Reconstruction Trial, done through the Pediatric Heart Network at 15 U.S. sites. It randomized 555 infants scheduled for the Norwood operation to either of the two shunt strategies.

One year after randomization, the incidence of death or need for heart transplant was 26% in patients getting the RVPAS and 36% in those getting the MBTS, a statistically significant 10% absolute difference in the primary end point in favor of the RVPAS. Although this was the primary end point, it did not tell the entire story.

Follow-up continued and after an average of 32 months, 16 additional deaths or heart transplants occurred in the RVPAS group compared with 7 of these events in the MBTS infants, a trend that led to the observation that the event curves may be converging over time.

Another worrisome finding was that unintended cardiac procedures such as balloon dilatations of the shunt or neoaorta, shunt revisions, or unplanned pulmonary artery reconstructions, were significantly more common in the RVPAS infants, 54%, compared with those who received MBTS, 44%. The RVPAS also produced smaller pulmonary arteries by the Nakata index.

By most other criteria, the two procedures produced similar outcomes. Time to extubation during surgery, duration of ventilation, and total days spent in the ICU and in the hospital were identical, as was the percentage of infants who required an open sternum or extracorporeal membrane oxygenation. The incidence of nonfatal serious adverse events was similar in the two arms, as was long-term right ventricular function. Infants treated with a RVPAS had the advantage of a significantly reduced need for cardiopulmonary resuscitation, 13%, compared with 20% in the MBTS infants.

“Although 12-month, transplant-free survival is higher with RVPAS, the emergence of later mortality with RVPAS is of concern. Continued follow-up of the cohort will be important to determine intermediate and long-term outcomes,” Dr. Ohye said.

Vitals

Major Findings: At 1 year, infants who received the RVPAS had a significant1absolute reduction in death or need for transplant vs. those who received the MBTS; after 1 year that rate was higher in the RVPAS patients.

Source of Data: The Single Ventricle Reconstruction Trial, involving 555 infants.

Disclosures: The National Heart, Lung, and Blood Institute sponsored the trial. Dr. Ohye had no conflicts.

ORLANDO — A growing number of American children have increased left ventricular mass, a marker for cardiovascular disease risk.

The finding was noted in a study that included 700 children and “is the first study to look at average left ventricular mass in the whole pediatric population,” according to Dr. David I. Crowley, a pediatric cardiologist at Cincinnati Children's Hospital.

In children with an average age of 10 years, mean left ventricular (LV) mass rose by a statistically significant 4% from 1986 to 2008. The prevalence of LV hypertrophy in the children more than doubled, from 7% to 15%, Dr. Crowley said at the annual scientific sessions of the American Heart Association.

The increase appears to be linked to obesity. In the 1986-1988 cohort of 350 children examined at Cincinnati Children's, the prevalence of overweight was 14% and of obesity was 5%. In a matched cohort of 350 children assessed in 2008, the prevalence of overweight was 15% but the prevalence of obesity soared to 19%. Results from a multivariate analysis showed that body mass index was a major determinant of LV mass, Dr. Crowley said.

The study included children aged 2-19 years. The participants came to Cincinnati Children's in 1986-1988 for an echocardiography examination because of a murmur, palpitations, syncope, or chest pain. All 350 children included in the analysis had normal cardiac anatomy and function, and none had systemic disease or a body mass index of 40 kg/m

Analysis of the echocardiographic data showed that, in addition to having larger hearts, the more recently evaluated children also had a greater prevalence of high-risk cardiac morphology. The prevalence of eccentric hypertrophy was 6% in the 1986-1988 group and 12% in the 2008 cohort. The prevalence of concentric hypertrophy also doubled in the more recent cohort.

Although average LV mass rose by only 4% from the older to more contemporary cohort, this difference is important, said Dr. Stephen R. Daniels. “When you look at a population and a value gets worse by even a small amount, it suggests that many more in the population may now be in a high-risk category,” said Dr. Daniels, a pediatric cardiologist at the University of Colorado in Denver.

Dr. Crowley had no financial conflicts.

In the 2008 cohort, 'the prevalence of obesity soared to 19%' vs. 5% in the 1986-1988 cohort.

Source DR. CROWLEY

ORLANDO — A growing number of American children have increased left ventricular mass, a marker for cardiovascular disease risk.

The finding was noted in a study that included 700 children and “is the first study to look at average left ventricular mass in the whole pediatric population,” according to Dr. David I. Crowley, a pediatric cardiologist at Cincinnati Children's Hospital.

In children with an average age of 10 years, mean left ventricular (LV) mass rose by a statistically significant 4% from 1986 to 2008. The prevalence of LV hypertrophy in the children more than doubled, from 7% to 15%, Dr. Crowley said at the annual scientific sessions of the American Heart Association.

The increase appears to be linked to obesity. In the 1986-1988 cohort of 350 children examined at Cincinnati Children's, the prevalence of overweight was 14% and of obesity was 5%. In a matched cohort of 350 children assessed in 2008, the prevalence of overweight was 15% but the prevalence of obesity soared to 19%. Results from a multivariate analysis showed that body mass index was a major determinant of LV mass, Dr. Crowley said.

The study included children aged 2-19 years. The participants came to Cincinnati Children's in 1986-1988 for an echocardiography examination because of a murmur, palpitations, syncope, or chest pain. All 350 children included in the analysis had normal cardiac anatomy and function, and none had systemic disease or a body mass index of 40 kg/m

Analysis of the echocardiographic data showed that, in addition to having larger hearts, the more recently evaluated children also had a greater prevalence of high-risk cardiac morphology. The prevalence of eccentric hypertrophy was 6% in the 1986-1988 group and 12% in the 2008 cohort. The prevalence of concentric hypertrophy also doubled in the more recent cohort.

Although average LV mass rose by only 4% from the older to more contemporary cohort, this difference is important, said Dr. Stephen R. Daniels. “When you look at a population and a value gets worse by even a small amount, it suggests that many more in the population may now be in a high-risk category,” said Dr. Daniels, a pediatric cardiologist at the University of Colorado in Denver.

Dr. Crowley had no financial conflicts.

In the 2008 cohort, 'the prevalence of obesity soared to 19%' vs. 5% in the 1986-1988 cohort.

Source DR. CROWLEY

ORLANDO — A growing number of American children have increased left ventricular mass, a marker for cardiovascular disease risk.

The finding was noted in a study that included 700 children and “is the first study to look at average left ventricular mass in the whole pediatric population,” according to Dr. David I. Crowley, a pediatric cardiologist at Cincinnati Children's Hospital.

In children with an average age of 10 years, mean left ventricular (LV) mass rose by a statistically significant 4% from 1986 to 2008. The prevalence of LV hypertrophy in the children more than doubled, from 7% to 15%, Dr. Crowley said at the annual scientific sessions of the American Heart Association.

The increase appears to be linked to obesity. In the 1986-1988 cohort of 350 children examined at Cincinnati Children's, the prevalence of overweight was 14% and of obesity was 5%. In a matched cohort of 350 children assessed in 2008, the prevalence of overweight was 15% but the prevalence of obesity soared to 19%. Results from a multivariate analysis showed that body mass index was a major determinant of LV mass, Dr. Crowley said.

The study included children aged 2-19 years. The participants came to Cincinnati Children's in 1986-1988 for an echocardiography examination because of a murmur, palpitations, syncope, or chest pain. All 350 children included in the analysis had normal cardiac anatomy and function, and none had systemic disease or a body mass index of 40 kg/m

Analysis of the echocardiographic data showed that, in addition to having larger hearts, the more recently evaluated children also had a greater prevalence of high-risk cardiac morphology. The prevalence of eccentric hypertrophy was 6% in the 1986-1988 group and 12% in the 2008 cohort. The prevalence of concentric hypertrophy also doubled in the more recent cohort.

Although average LV mass rose by only 4% from the older to more contemporary cohort, this difference is important, said Dr. Stephen R. Daniels. “When you look at a population and a value gets worse by even a small amount, it suggests that many more in the population may now be in a high-risk category,” said Dr. Daniels, a pediatric cardiologist at the University of Colorado in Denver.

Dr. Crowley had no financial conflicts.

In the 2008 cohort, 'the prevalence of obesity soared to 19%' vs. 5% in the 1986-1988 cohort.

Source DR. CROWLEY

ORLANDO — Patients who had their coronary calcium levels imaged by CT angiography had substantially better survival than did similar patients who underwent standard management, an observational study has shown.

The findings, which involved more than 4,000 patients followed for more than 6 years, could have implications for insurance reimbursement of CT angiography, Dr. Matthew J. Budoff said at the annual scientific sessions of the American Heart Association. He hypothesized that the mortality difference between patients who underwent CT imaging and those who did not may be explained by improved compliance with therapy among patients who were able to see the extent of their calcified coronary disease.

Although several payers including United Healthcare, Aetna, Medicare, and Medicaid currently reimburse for CT angiography, the national policy of Blue Cross/Blue Shield is not to cover these examinations. The Blues' stated policy is that they will not cover new diagnostic tests until their value in improving patient outcomes is proved, Dr. Budoff said. He believes the new data mean this standard has now been met, but he acknowledged that the study was observational and not a prospective, randomized trial. Nonetheless, the size and duration of the study, as well as the striking magnitude of beneficial effect, should be persuasive, said Dr. Budoff, program director of cardiology at the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center.

In his study, 2,538 symptomatic patients referred for assessment of possible coronary disease and evaluated by coronary CT had a 52% reduced risk of all-cause death during an average 6.7-year follow-up compared with a similar group of 1,706 patients whose work-up did not include CT angiography.

“Increased awareness of coronary artery disease severity among people undergoing CT angiography may have contributed to their survival,” Dr. Budoff said.

“Probable mechanisms include increased adherence to and use of anti-atherosclerotic therapies, such as statins, angiotensin-converting enzyme inhibitors, and anti-platelet drugs” such as aspirin, he added.

Dr. Budoff shows patients in his clinic who undergo coronary CT and have coronary calcium six images of their coronary arteries that depict the calcium deposits and stenoses.

“I think that this is something that leads to compliance. It's very black and white. Patients can see their plaque and stenosis and know they need treatment,” he said in an interview. Patients also receive their calcium scores.

The total of 4,244 symptomatic patients in the study had an average age of 58, and 62% did not have known coronary artery disease. The patients who underwent coronary CT and those who received standard care without coronary CT imaging were treated in the academic cardiology clinic at Harbor-UCLA. The two groups were matched by age, gender, the time when they were first seen, and their conventional cardiac risk factors.

All patients undergoing coronary CT had the examination covered by their insurance providers; none of the patients paid for the exam out of pocket. One factor that the study did not control for was socioeconomic status. The patients who did not undergo CT angiography may have been, as a group, somewhat poorer than those who had CT examinations, Dr. Budoff said.

During an average 80-month follow-up the all-cause mortality rate was 3% in patients who had CT examinations and 11% in those who did not, a statistically significant difference. Mortality rates began to diverge between the two groups after about 3 years, and then continued to diverge.

In a multivariate analysis that controlled for age, gender, and coronary risk factors, patients who had standard care had a fourfold higher risk of dying than did those who had CT angiography.

Dr. Budoff has served on the speakers bureau for GE, a company that markets CT equipment. None of his associates in the study had any financial disclosures.

'It's very black and white. Patients can see their plaque and stenosis and know they need treatment.'

Source DR. BUDOFF

ORLANDO — Patients who had their coronary calcium levels imaged by CT angiography had substantially better survival than did similar patients who underwent standard management, an observational study has shown.

The findings, which involved more than 4,000 patients followed for more than 6 years, could have implications for insurance reimbursement of CT angiography, Dr. Matthew J. Budoff said at the annual scientific sessions of the American Heart Association. He hypothesized that the mortality difference between patients who underwent CT imaging and those who did not may be explained by improved compliance with therapy among patients who were able to see the extent of their calcified coronary disease.

Although several payers including United Healthcare, Aetna, Medicare, and Medicaid currently reimburse for CT angiography, the national policy of Blue Cross/Blue Shield is not to cover these examinations. The Blues' stated policy is that they will not cover new diagnostic tests until their value in improving patient outcomes is proved, Dr. Budoff said. He believes the new data mean this standard has now been met, but he acknowledged that the study was observational and not a prospective, randomized trial. Nonetheless, the size and duration of the study, as well as the striking magnitude of beneficial effect, should be persuasive, said Dr. Budoff, program director of cardiology at the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center.

In his study, 2,538 symptomatic patients referred for assessment of possible coronary disease and evaluated by coronary CT had a 52% reduced risk of all-cause death during an average 6.7-year follow-up compared with a similar group of 1,706 patients whose work-up did not include CT angiography.

“Increased awareness of coronary artery disease severity among people undergoing CT angiography may have contributed to their survival,” Dr. Budoff said.

“Probable mechanisms include increased adherence to and use of anti-atherosclerotic therapies, such as statins, angiotensin-converting enzyme inhibitors, and anti-platelet drugs” such as aspirin, he added.

Dr. Budoff shows patients in his clinic who undergo coronary CT and have coronary calcium six images of their coronary arteries that depict the calcium deposits and stenoses.

“I think that this is something that leads to compliance. It's very black and white. Patients can see their plaque and stenosis and know they need treatment,” he said in an interview. Patients also receive their calcium scores.

The total of 4,244 symptomatic patients in the study had an average age of 58, and 62% did not have known coronary artery disease. The patients who underwent coronary CT and those who received standard care without coronary CT imaging were treated in the academic cardiology clinic at Harbor-UCLA. The two groups were matched by age, gender, the time when they were first seen, and their conventional cardiac risk factors.

All patients undergoing coronary CT had the examination covered by their insurance providers; none of the patients paid for the exam out of pocket. One factor that the study did not control for was socioeconomic status. The patients who did not undergo CT angiography may have been, as a group, somewhat poorer than those who had CT examinations, Dr. Budoff said.

During an average 80-month follow-up the all-cause mortality rate was 3% in patients who had CT examinations and 11% in those who did not, a statistically significant difference. Mortality rates began to diverge between the two groups after about 3 years, and then continued to diverge.

In a multivariate analysis that controlled for age, gender, and coronary risk factors, patients who had standard care had a fourfold higher risk of dying than did those who had CT angiography.

Dr. Budoff has served on the speakers bureau for GE, a company that markets CT equipment. None of his associates in the study had any financial disclosures.

'It's very black and white. Patients can see their plaque and stenosis and know they need treatment.'

Source DR. BUDOFF

ORLANDO — Patients who had their coronary calcium levels imaged by CT angiography had substantially better survival than did similar patients who underwent standard management, an observational study has shown.

The findings, which involved more than 4,000 patients followed for more than 6 years, could have implications for insurance reimbursement of CT angiography, Dr. Matthew J. Budoff said at the annual scientific sessions of the American Heart Association. He hypothesized that the mortality difference between patients who underwent CT imaging and those who did not may be explained by improved compliance with therapy among patients who were able to see the extent of their calcified coronary disease.

Although several payers including United Healthcare, Aetna, Medicare, and Medicaid currently reimburse for CT angiography, the national policy of Blue Cross/Blue Shield is not to cover these examinations. The Blues' stated policy is that they will not cover new diagnostic tests until their value in improving patient outcomes is proved, Dr. Budoff said. He believes the new data mean this standard has now been met, but he acknowledged that the study was observational and not a prospective, randomized trial. Nonetheless, the size and duration of the study, as well as the striking magnitude of beneficial effect, should be persuasive, said Dr. Budoff, program director of cardiology at the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center.

In his study, 2,538 symptomatic patients referred for assessment of possible coronary disease and evaluated by coronary CT had a 52% reduced risk of all-cause death during an average 6.7-year follow-up compared with a similar group of 1,706 patients whose work-up did not include CT angiography.

“Increased awareness of coronary artery disease severity among people undergoing CT angiography may have contributed to their survival,” Dr. Budoff said.

“Probable mechanisms include increased adherence to and use of anti-atherosclerotic therapies, such as statins, angiotensin-converting enzyme inhibitors, and anti-platelet drugs” such as aspirin, he added.

Dr. Budoff shows patients in his clinic who undergo coronary CT and have coronary calcium six images of their coronary arteries that depict the calcium deposits and stenoses.

“I think that this is something that leads to compliance. It's very black and white. Patients can see their plaque and stenosis and know they need treatment,” he said in an interview. Patients also receive their calcium scores.

The total of 4,244 symptomatic patients in the study had an average age of 58, and 62% did not have known coronary artery disease. The patients who underwent coronary CT and those who received standard care without coronary CT imaging were treated in the academic cardiology clinic at Harbor-UCLA. The two groups were matched by age, gender, the time when they were first seen, and their conventional cardiac risk factors.

All patients undergoing coronary CT had the examination covered by their insurance providers; none of the patients paid for the exam out of pocket. One factor that the study did not control for was socioeconomic status. The patients who did not undergo CT angiography may have been, as a group, somewhat poorer than those who had CT examinations, Dr. Budoff said.

During an average 80-month follow-up the all-cause mortality rate was 3% in patients who had CT examinations and 11% in those who did not, a statistically significant difference. Mortality rates began to diverge between the two groups after about 3 years, and then continued to diverge.

In a multivariate analysis that controlled for age, gender, and coronary risk factors, patients who had standard care had a fourfold higher risk of dying than did those who had CT angiography.

Dr. Budoff has served on the speakers bureau for GE, a company that markets CT equipment. None of his associates in the study had any financial disclosures.

'It's very black and white. Patients can see their plaque and stenosis and know they need treatment.'

Source DR. BUDOFF

ORLANDO — During long-term follow-up after pregnancy, women with congenital heart disease had a 12% rate of late cardiac events in a series of 318 patients followed at one center for a median of 2.6 years.

The analysis also identified four clinical factors that flagged women with congenital heart disease (CHD) who faced the highest risk for a late event (starting more than 6 months after delivery). Women with one of these risk factors had a 27% rate of long-term cardiac events, women with more than one had a 47% rate, whereas women with none of them had an 8% rate, Dr. Olga H. Balint said at the annual scientific sessions of the American Heart Association.

“We can use this data to discuss with patients” the risk they face from pregnancy, said Dr. Balint, a physician in the pregnancy and heart disease research program at the University of Toronto. The findings highlight the significance of cardiac events that occur before or during pregnancy, a factor that raised the risk for a late event by 2.5-fold independent of any other risk. “These patients are most likely to need intervention after pregnancy.”

The other three significant independent risk factors for late cardiac events were as follows:

▸ Subpulmonary ventricular dysfunction, pulmonary regurgitation, or both, which conferred a 3.4-fold independent increased risk for a late event.

▸ Subaortic ventricular dysfunction, which produced an independent threefold increased risk.

▸ Left heart obstruction, which linked with a 2.5-fold increased risk.

The late events, which occurred following 50 of the total 405 deliveries, were most frequently arrhythmia, with pulmonary edema as the next most common event. Three late events were cardiac arrest or death, and one was a stroke. This 12% rate of late cardiac events matched the 12% rate of cardiac events that preceded pregnancy and the 11% rate during pregnancy.

The women in the Toronto series had an average age of 28, and 66% were nulliparous prior to the index pregnancy. Dr. Balint stressed that parity was not a significant univariate risk factor for late cardiac events nor was it a significant risk factor in the multivariate analysis.

The most common congenital disease in the series, which ranged in time from 1995 to 2007, was a shunt lesion, in 87 women, followed by tetralogy of Fallot in 70, aortic coarctation in 52, and congenital aortic stenosis in 45 patients.

These findings have increasing relevance to U.S. practice because the number of American women with CHD who became pregnant steadily rose in 1998-2006, according to a study reported in a poster at the meeting.

Using data from nearly 38 million pregnant U.S. women hospitalized during that period and collected by the Nationwide Inpatient Sample, Dr. Omar K. Siddiqi and his associates found that during those 9 years the number of deliveries from women with CHD rose steadily by an overall 26%, reaching roughly 3,500 deliveries in both 2005 and 2006, compared with an 11% rise in U.S. adults with CHD during the same period.

Pregnant U.S. women with CHD during the study period matched their pregnant counterparts without congenital disease by their average age, 27, but their risk for peripartum complications or death was far higher, said Dr. Siddiqi, a physician at the University of Pennsylvania in Philadelphia, and his associates. Risks increased in pregnant women with CHD 22-fold for heart failure, 11-fold for arrhythmia, 31-fold for stroke, and 12-fold for death, compared with pregnant women without CHD.

Vitals

Major Findings: Women with congenital heart disease had a 12% rate of late cardiac events after pregnancy. The strongest independent risk factor for such an event was a cardiac event before or during pregnancy.

Source of Data: Analysis of 318 women, with a total of 405 deliveries, at one center in Toronto.

Disclosures: Dr. Balint and her associates had no financial disclosures to report.

ORLANDO — During long-term follow-up after pregnancy, women with congenital heart disease had a 12% rate of late cardiac events in a series of 318 patients followed at one center for a median of 2.6 years.

The analysis also identified four clinical factors that flagged women with congenital heart disease (CHD) who faced the highest risk for a late event (starting more than 6 months after delivery). Women with one of these risk factors had a 27% rate of long-term cardiac events, women with more than one had a 47% rate, whereas women with none of them had an 8% rate, Dr. Olga H. Balint said at the annual scientific sessions of the American Heart Association.

“We can use this data to discuss with patients” the risk they face from pregnancy, said Dr. Balint, a physician in the pregnancy and heart disease research program at the University of Toronto. The findings highlight the significance of cardiac events that occur before or during pregnancy, a factor that raised the risk for a late event by 2.5-fold independent of any other risk. “These patients are most likely to need intervention after pregnancy.”

The other three significant independent risk factors for late cardiac events were as follows:

▸ Subpulmonary ventricular dysfunction, pulmonary regurgitation, or both, which conferred a 3.4-fold independent increased risk for a late event.

▸ Subaortic ventricular dysfunction, which produced an independent threefold increased risk.

▸ Left heart obstruction, which linked with a 2.5-fold increased risk.

The late events, which occurred following 50 of the total 405 deliveries, were most frequently arrhythmia, with pulmonary edema as the next most common event. Three late events were cardiac arrest or death, and one was a stroke. This 12% rate of late cardiac events matched the 12% rate of cardiac events that preceded pregnancy and the 11% rate during pregnancy.

The women in the Toronto series had an average age of 28, and 66% were nulliparous prior to the index pregnancy. Dr. Balint stressed that parity was not a significant univariate risk factor for late cardiac events nor was it a significant risk factor in the multivariate analysis.

The most common congenital disease in the series, which ranged in time from 1995 to 2007, was a shunt lesion, in 87 women, followed by tetralogy of Fallot in 70, aortic coarctation in 52, and congenital aortic stenosis in 45 patients.

These findings have increasing relevance to U.S. practice because the number of American women with CHD who became pregnant steadily rose in 1998-2006, according to a study reported in a poster at the meeting.

Using data from nearly 38 million pregnant U.S. women hospitalized during that period and collected by the Nationwide Inpatient Sample, Dr. Omar K. Siddiqi and his associates found that during those 9 years the number of deliveries from women with CHD rose steadily by an overall 26%, reaching roughly 3,500 deliveries in both 2005 and 2006, compared with an 11% rise in U.S. adults with CHD during the same period.

Pregnant U.S. women with CHD during the study period matched their pregnant counterparts without congenital disease by their average age, 27, but their risk for peripartum complications or death was far higher, said Dr. Siddiqi, a physician at the University of Pennsylvania in Philadelphia, and his associates. Risks increased in pregnant women with CHD 22-fold for heart failure, 11-fold for arrhythmia, 31-fold for stroke, and 12-fold for death, compared with pregnant women without CHD.

Vitals

Major Findings: Women with congenital heart disease had a 12% rate of late cardiac events after pregnancy. The strongest independent risk factor for such an event was a cardiac event before or during pregnancy.

Source of Data: Analysis of 318 women, with a total of 405 deliveries, at one center in Toronto.

Disclosures: Dr. Balint and her associates had no financial disclosures to report.

ORLANDO — During long-term follow-up after pregnancy, women with congenital heart disease had a 12% rate of late cardiac events in a series of 318 patients followed at one center for a median of 2.6 years.

The analysis also identified four clinical factors that flagged women with congenital heart disease (CHD) who faced the highest risk for a late event (starting more than 6 months after delivery). Women with one of these risk factors had a 27% rate of long-term cardiac events, women with more than one had a 47% rate, whereas women with none of them had an 8% rate, Dr. Olga H. Balint said at the annual scientific sessions of the American Heart Association.

“We can use this data to discuss with patients” the risk they face from pregnancy, said Dr. Balint, a physician in the pregnancy and heart disease research program at the University of Toronto. The findings highlight the significance of cardiac events that occur before or during pregnancy, a factor that raised the risk for a late event by 2.5-fold independent of any other risk. “These patients are most likely to need intervention after pregnancy.”

The other three significant independent risk factors for late cardiac events were as follows:

▸ Subpulmonary ventricular dysfunction, pulmonary regurgitation, or both, which conferred a 3.4-fold independent increased risk for a late event.

▸ Subaortic ventricular dysfunction, which produced an independent threefold increased risk.

▸ Left heart obstruction, which linked with a 2.5-fold increased risk.

The late events, which occurred following 50 of the total 405 deliveries, were most frequently arrhythmia, with pulmonary edema as the next most common event. Three late events were cardiac arrest or death, and one was a stroke. This 12% rate of late cardiac events matched the 12% rate of cardiac events that preceded pregnancy and the 11% rate during pregnancy.

The women in the Toronto series had an average age of 28, and 66% were nulliparous prior to the index pregnancy. Dr. Balint stressed that parity was not a significant univariate risk factor for late cardiac events nor was it a significant risk factor in the multivariate analysis.

The most common congenital disease in the series, which ranged in time from 1995 to 2007, was a shunt lesion, in 87 women, followed by tetralogy of Fallot in 70, aortic coarctation in 52, and congenital aortic stenosis in 45 patients.

These findings have increasing relevance to U.S. practice because the number of American women with CHD who became pregnant steadily rose in 1998-2006, according to a study reported in a poster at the meeting.

Using data from nearly 38 million pregnant U.S. women hospitalized during that period and collected by the Nationwide Inpatient Sample, Dr. Omar K. Siddiqi and his associates found that during those 9 years the number of deliveries from women with CHD rose steadily by an overall 26%, reaching roughly 3,500 deliveries in both 2005 and 2006, compared with an 11% rise in U.S. adults with CHD during the same period.

Pregnant U.S. women with CHD during the study period matched their pregnant counterparts without congenital disease by their average age, 27, but their risk for peripartum complications or death was far higher, said Dr. Siddiqi, a physician at the University of Pennsylvania in Philadelphia, and his associates. Risks increased in pregnant women with CHD 22-fold for heart failure, 11-fold for arrhythmia, 31-fold for stroke, and 12-fold for death, compared with pregnant women without CHD.

Vitals

Major Findings: Women with congenital heart disease had a 12% rate of late cardiac events after pregnancy. The strongest independent risk factor for such an event was a cardiac event before or during pregnancy.

Source of Data: Analysis of 318 women, with a total of 405 deliveries, at one center in Toronto.

Disclosures: Dr. Balint and her associates had no financial disclosures to report.

ORLANDO — Chronotropic index, a measure of heart rate response in an exercise test, significantly correlated with the risk for postpartum adverse cardiac events in a review of 83 women with congenital heart disease.

The finding shows that chronotropic index can provide valuable guidance when counseling women with congenital heart disease about the risk they face from pregnancy for triggering a cardiac or neonatal event, Dr. George K. Lui said at the annual scientific sessions of the American Heart Association.

The chronotropic index “is a helpful tool,” along with other risk markers such as a history of heart failure or of sustained arrhythmias, said Dr. Lui, director of adult congenital heart disease at Montefiore Medical Center in the Bronx, N.Y. “Stress testing adds to the risk assessment and counseling,” of these women, “especially in patients at borderline risk,” he said in an interview.

His study used data collected through the Alliance for Adult Research in Congenital Cardiology at 13 centers in the United States and Canada.

The 83 women had undergone a cardiopulmonary exercise test within the period starting 2 years prior to their pregnancy and running through the end of their first trimester. Their average age was 29 years, 88% had New York Heart Association class I heart failure, 12% had class II symptoms, and none were cyanotic.

The most common congenital heart disease was repaired tetralogy of Fallot, in 35%; D-transposition of the great arteries, in 29%; left-sided obstruction lesions, in 11%; and right-sided obstructive lesions, in 10%.

The study included outcomes from the 89 pregnancies.

The chronotropic index calculation involved subtracting a woman's resting heart rate from her peak exercise heart rate and dividing the difference by 220 minus her age and minus her resting heart rate.

According to a survey of healthy adults published in 1989, normal chronotropic index is 1.0, with a normal range of 0.8-1.3 (J. Cardiovasc. Electrophysiol. 1989;3:176-80).

The women in Dr. Lui's study had an average chronotropic index of 0.75. More than half had a chronotropic index below the normal range cutoff of 0.80.

During pregnancy, 15 of the women had a cardiac event, including 12 with heart failure, 6 with a sustained arrhythmia, and 1 death. Also, among the 89 pregnancies were 17 neonatal events, including 16 preterm deliveries, 7 neonates who were small for gestational age, and 3 episodes of respiratory distress syndrome.

Women who had a chronotropic index of less than 0.80 had a significantly increased risk for both a cardiac event and neonatal event.

A univariate analysis indicated that women with a chronotropic index of 0.80 or higher were 35% less likely to have a cardiac event and their pregnancies were 27% less likely to have a neonatal event, compared with women with a chronotropic index of less than 0.80.

Results of multivariate analysis that controlled for treatment with an antiarrhythmic medication showed that a chronotropic index of 0.80 or higher lowered the risk for a maternal cardiac event by 30%.

Dr. Lui stated that he had no financial disclosures.

Women who had a chronotropic index of less than 0.80 had an increased risk for cardiac and neonatal events.

Source DR. LUI

ORLANDO — Chronotropic index, a measure of heart rate response in an exercise test, significantly correlated with the risk for postpartum adverse cardiac events in a review of 83 women with congenital heart disease.

The finding shows that chronotropic index can provide valuable guidance when counseling women with congenital heart disease about the risk they face from pregnancy for triggering a cardiac or neonatal event, Dr. George K. Lui said at the annual scientific sessions of the American Heart Association.

The chronotropic index “is a helpful tool,” along with other risk markers such as a history of heart failure or of sustained arrhythmias, said Dr. Lui, director of adult congenital heart disease at Montefiore Medical Center in the Bronx, N.Y. “Stress testing adds to the risk assessment and counseling,” of these women, “especially in patients at borderline risk,” he said in an interview.

His study used data collected through the Alliance for Adult Research in Congenital Cardiology at 13 centers in the United States and Canada.

The 83 women had undergone a cardiopulmonary exercise test within the period starting 2 years prior to their pregnancy and running through the end of their first trimester. Their average age was 29 years, 88% had New York Heart Association class I heart failure, 12% had class II symptoms, and none were cyanotic.

The most common congenital heart disease was repaired tetralogy of Fallot, in 35%; D-transposition of the great arteries, in 29%; left-sided obstruction lesions, in 11%; and right-sided obstructive lesions, in 10%.

The study included outcomes from the 89 pregnancies.

The chronotropic index calculation involved subtracting a woman's resting heart rate from her peak exercise heart rate and dividing the difference by 220 minus her age and minus her resting heart rate.

According to a survey of healthy adults published in 1989, normal chronotropic index is 1.0, with a normal range of 0.8-1.3 (J. Cardiovasc. Electrophysiol. 1989;3:176-80).

The women in Dr. Lui's study had an average chronotropic index of 0.75. More than half had a chronotropic index below the normal range cutoff of 0.80.

During pregnancy, 15 of the women had a cardiac event, including 12 with heart failure, 6 with a sustained arrhythmia, and 1 death. Also, among the 89 pregnancies were 17 neonatal events, including 16 preterm deliveries, 7 neonates who were small for gestational age, and 3 episodes of respiratory distress syndrome.

Women who had a chronotropic index of less than 0.80 had a significantly increased risk for both a cardiac event and neonatal event.

A univariate analysis indicated that women with a chronotropic index of 0.80 or higher were 35% less likely to have a cardiac event and their pregnancies were 27% less likely to have a neonatal event, compared with women with a chronotropic index of less than 0.80.

Results of multivariate analysis that controlled for treatment with an antiarrhythmic medication showed that a chronotropic index of 0.80 or higher lowered the risk for a maternal cardiac event by 30%.

Dr. Lui stated that he had no financial disclosures.

Women who had a chronotropic index of less than 0.80 had an increased risk for cardiac and neonatal events.

Source DR. LUI

ORLANDO — Chronotropic index, a measure of heart rate response in an exercise test, significantly correlated with the risk for postpartum adverse cardiac events in a review of 83 women with congenital heart disease.

The finding shows that chronotropic index can provide valuable guidance when counseling women with congenital heart disease about the risk they face from pregnancy for triggering a cardiac or neonatal event, Dr. George K. Lui said at the annual scientific sessions of the American Heart Association.

The chronotropic index “is a helpful tool,” along with other risk markers such as a history of heart failure or of sustained arrhythmias, said Dr. Lui, director of adult congenital heart disease at Montefiore Medical Center in the Bronx, N.Y. “Stress testing adds to the risk assessment and counseling,” of these women, “especially in patients at borderline risk,” he said in an interview.

His study used data collected through the Alliance for Adult Research in Congenital Cardiology at 13 centers in the United States and Canada.

The 83 women had undergone a cardiopulmonary exercise test within the period starting 2 years prior to their pregnancy and running through the end of their first trimester. Their average age was 29 years, 88% had New York Heart Association class I heart failure, 12% had class II symptoms, and none were cyanotic.

The most common congenital heart disease was repaired tetralogy of Fallot, in 35%; D-transposition of the great arteries, in 29%; left-sided obstruction lesions, in 11%; and right-sided obstructive lesions, in 10%.

The study included outcomes from the 89 pregnancies.

The chronotropic index calculation involved subtracting a woman's resting heart rate from her peak exercise heart rate and dividing the difference by 220 minus her age and minus her resting heart rate.

According to a survey of healthy adults published in 1989, normal chronotropic index is 1.0, with a normal range of 0.8-1.3 (J. Cardiovasc. Electrophysiol. 1989;3:176-80).

The women in Dr. Lui's study had an average chronotropic index of 0.75. More than half had a chronotropic index below the normal range cutoff of 0.80.

During pregnancy, 15 of the women had a cardiac event, including 12 with heart failure, 6 with a sustained arrhythmia, and 1 death. Also, among the 89 pregnancies were 17 neonatal events, including 16 preterm deliveries, 7 neonates who were small for gestational age, and 3 episodes of respiratory distress syndrome.

Women who had a chronotropic index of less than 0.80 had a significantly increased risk for both a cardiac event and neonatal event.

A univariate analysis indicated that women with a chronotropic index of 0.80 or higher were 35% less likely to have a cardiac event and their pregnancies were 27% less likely to have a neonatal event, compared with women with a chronotropic index of less than 0.80.

Results of multivariate analysis that controlled for treatment with an antiarrhythmic medication showed that a chronotropic index of 0.80 or higher lowered the risk for a maternal cardiac event by 30%.

Dr. Lui stated that he had no financial disclosures.

Women who had a chronotropic index of less than 0.80 had an increased risk for cardiac and neonatal events.

Source DR. LUI

ORLANDO — Infants born with a congenital heart disease during 1990-1999 who then underwent care at a tertiary center had an 89% actuarial survival rate to age 18 or older, based on data of more than 3,800 patients at one Belgium center.

The rate was a significant improvement over an 85% survival to adulthood rate for infants with congenital heart disease born during 1980-1989 and managed at the same center, and the 82% survival to age 18 or older in infants born during 1970-1979, Philip Moons, Ph.D., said at the annual scientific sessions of the American Heart Association.

Dr. Moons and associates used the clinical database of the congenital heart disease program at Catholic University in Leuven, Belgium, which included 17,044 patients born with gross structural abnormalities of the heart or intrathoracic great vessels. Twenty-three percent were born during 1990–1999;24% before 1970, 10% during 1970–1979, 21% during 1980–1989, and 17% in 2000 or more recently.

The most common congenital diseases for the entire group was ventricular septal defect, in 22%, followed by atrial septal defect in 15%, and pulmonary valve abnormality in 10%.

In the 1990-1999 group, mortality from congenital heart disease occurred because of cardiac failure in 56%, postoperative complications in 22%, and perioperative complications in 9%. In the 1990-1999 group, mortality during follow-up was 99% in patients with mild congenital heart disease, 90% in those with moderate disease, and 59% in patients with a complex abnormality, said Dr. Moons, a researcher at Catholic University who reported no financial conflicts of interest.

ORLANDO — Infants born with a congenital heart disease during 1990-1999 who then underwent care at a tertiary center had an 89% actuarial survival rate to age 18 or older, based on data of more than 3,800 patients at one Belgium center.

The rate was a significant improvement over an 85% survival to adulthood rate for infants with congenital heart disease born during 1980-1989 and managed at the same center, and the 82% survival to age 18 or older in infants born during 1970-1979, Philip Moons, Ph.D., said at the annual scientific sessions of the American Heart Association.

Dr. Moons and associates used the clinical database of the congenital heart disease program at Catholic University in Leuven, Belgium, which included 17,044 patients born with gross structural abnormalities of the heart or intrathoracic great vessels. Twenty-three percent were born during 1990–1999;24% before 1970, 10% during 1970–1979, 21% during 1980–1989, and 17% in 2000 or more recently.

The most common congenital diseases for the entire group was ventricular septal defect, in 22%, followed by atrial septal defect in 15%, and pulmonary valve abnormality in 10%.

In the 1990-1999 group, mortality from congenital heart disease occurred because of cardiac failure in 56%, postoperative complications in 22%, and perioperative complications in 9%. In the 1990-1999 group, mortality during follow-up was 99% in patients with mild congenital heart disease, 90% in those with moderate disease, and 59% in patients with a complex abnormality, said Dr. Moons, a researcher at Catholic University who reported no financial conflicts of interest.

ORLANDO — Infants born with a congenital heart disease during 1990-1999 who then underwent care at a tertiary center had an 89% actuarial survival rate to age 18 or older, based on data of more than 3,800 patients at one Belgium center.

The rate was a significant improvement over an 85% survival to adulthood rate for infants with congenital heart disease born during 1980-1989 and managed at the same center, and the 82% survival to age 18 or older in infants born during 1970-1979, Philip Moons, Ph.D., said at the annual scientific sessions of the American Heart Association.

Dr. Moons and associates used the clinical database of the congenital heart disease program at Catholic University in Leuven, Belgium, which included 17,044 patients born with gross structural abnormalities of the heart or intrathoracic great vessels. Twenty-three percent were born during 1990–1999;24% before 1970, 10% during 1970–1979, 21% during 1980–1989, and 17% in 2000 or more recently.

The most common congenital diseases for the entire group was ventricular septal defect, in 22%, followed by atrial septal defect in 15%, and pulmonary valve abnormality in 10%.

In the 1990-1999 group, mortality from congenital heart disease occurred because of cardiac failure in 56%, postoperative complications in 22%, and perioperative complications in 9%. In the 1990-1999 group, mortality during follow-up was 99% in patients with mild congenital heart disease, 90% in those with moderate disease, and 59% in patients with a complex abnormality, said Dr. Moons, a researcher at Catholic University who reported no financial conflicts of interest.

ORLANDO — High blood levels of a brain natriuretic peptide were associated with poor cognitive function in a study of 950 community-dwelling, healthy, elderly adults.

“This is the first time this [association] has been shown,” Dr. Lori B. Daniels said at the annual scientific sessions of the American Heart Association.

Elevated levels of natriuretic peptide mark the presence of a variety of disease states, especially heart failure, said Dr. Daniels. She suggested several mechanisms that might link production of natriuretic peptide to poor cognitive function, including reduced cardiac output that drops oxygen or nutrient supplies to the brain and atrial fibrillation that creates microemboli.

Another issue is “which comes first, cardiovascular disease or poor cognitive performance,” said Dr. Daniels, a cardiologist at the University of California, San Diego.

Patients analyzed were enrolled in the Rancho Bernardo study in the early 1970s. Of the more than 5,000 community-dwelling adults in the study, 950 underwent a battery of cognitive function tests from 1997 to 1999 and had blood specimens drawn; they were the focus of the new analysis.

The average age of the 950 participants was 77 years; 61% were women. Two-thirds were hypertensive, 4% were current smokers, 49% drank three or more alcoholic drinks per week, and 6% had a history of stroke.

The researchers used three tests to evaluate cognitive function: the Mini-Mental State Exam (MMSE), which assessed features such as orientation, attention, and recall; the Trail-Making Test B, which gauged executive function; and a category fluency test that asked participants to name as many animals as they could in 1 minute.

The MMSE identified poor function in 7%, the trail-making test B identified poor function in 30%, and category fluency identified poor function in 15%.

Natriuretic peptide levels in the blood specimens were measured using a test that detects N-terminal pro-B-type natriuretic peptide (NT-proBNP). Natriuretic peptide measurements were considered low if the level was less than 450 pg/mL, and high if the level was 450 pg/mL or greater. Among the 950 participants, 79% had a low level and 21% had a high level.

People with high levels of NT-proBNP had significantly worse results in all three tests, compared with those who had low levels. In the low level group, poor cognitive scores occurred in 5%, 23%, and 12% of subjects for the three cognitive function tests, respectively. In the high level group, 17%, 54%, and 26% of the subjects scored poorly on the three tests, respectively.

When the results were adjusted for age, education, body mass index, exercise, alcohol use, and smoking, participants with high NT-proBNP levels had significantly worse cognitive function scores on the MMSE and the Trail-Making Test B. Poor scores for category fluency were lower in people with high NT-proBNP in the fully-adjusted model, but the difference fell short of statistical significance relative to those with low NT-proBNP.

Dr. Daniels received research support from Roche Diagnostics, which markets an NT-proBNP assay.

ORLANDO — High blood levels of a brain natriuretic peptide were associated with poor cognitive function in a study of 950 community-dwelling, healthy, elderly adults.

“This is the first time this [association] has been shown,” Dr. Lori B. Daniels said at the annual scientific sessions of the American Heart Association.

Elevated levels of natriuretic peptide mark the presence of a variety of disease states, especially heart failure, said Dr. Daniels. She suggested several mechanisms that might link production of natriuretic peptide to poor cognitive function, including reduced cardiac output that drops oxygen or nutrient supplies to the brain and atrial fibrillation that creates microemboli.

Another issue is “which comes first, cardiovascular disease or poor cognitive performance,” said Dr. Daniels, a cardiologist at the University of California, San Diego.

Patients analyzed were enrolled in the Rancho Bernardo study in the early 1970s. Of the more than 5,000 community-dwelling adults in the study, 950 underwent a battery of cognitive function tests from 1997 to 1999 and had blood specimens drawn; they were the focus of the new analysis.

The average age of the 950 participants was 77 years; 61% were women. Two-thirds were hypertensive, 4% were current smokers, 49% drank three or more alcoholic drinks per week, and 6% had a history of stroke.

The researchers used three tests to evaluate cognitive function: the Mini-Mental State Exam (MMSE), which assessed features such as orientation, attention, and recall; the Trail-Making Test B, which gauged executive function; and a category fluency test that asked participants to name as many animals as they could in 1 minute.

The MMSE identified poor function in 7%, the trail-making test B identified poor function in 30%, and category fluency identified poor function in 15%.

Natriuretic peptide levels in the blood specimens were measured using a test that detects N-terminal pro-B-type natriuretic peptide (NT-proBNP). Natriuretic peptide measurements were considered low if the level was less than 450 pg/mL, and high if the level was 450 pg/mL or greater. Among the 950 participants, 79% had a low level and 21% had a high level.

People with high levels of NT-proBNP had significantly worse results in all three tests, compared with those who had low levels. In the low level group, poor cognitive scores occurred in 5%, 23%, and 12% of subjects for the three cognitive function tests, respectively. In the high level group, 17%, 54%, and 26% of the subjects scored poorly on the three tests, respectively.

When the results were adjusted for age, education, body mass index, exercise, alcohol use, and smoking, participants with high NT-proBNP levels had significantly worse cognitive function scores on the MMSE and the Trail-Making Test B. Poor scores for category fluency were lower in people with high NT-proBNP in the fully-adjusted model, but the difference fell short of statistical significance relative to those with low NT-proBNP.

Dr. Daniels received research support from Roche Diagnostics, which markets an NT-proBNP assay.

ORLANDO — High blood levels of a brain natriuretic peptide were associated with poor cognitive function in a study of 950 community-dwelling, healthy, elderly adults.

“This is the first time this [association] has been shown,” Dr. Lori B. Daniels said at the annual scientific sessions of the American Heart Association.

Elevated levels of natriuretic peptide mark the presence of a variety of disease states, especially heart failure, said Dr. Daniels. She suggested several mechanisms that might link production of natriuretic peptide to poor cognitive function, including reduced cardiac output that drops oxygen or nutrient supplies to the brain and atrial fibrillation that creates microemboli.

Another issue is “which comes first, cardiovascular disease or poor cognitive performance,” said Dr. Daniels, a cardiologist at the University of California, San Diego.

Patients analyzed were enrolled in the Rancho Bernardo study in the early 1970s. Of the more than 5,000 community-dwelling adults in the study, 950 underwent a battery of cognitive function tests from 1997 to 1999 and had blood specimens drawn; they were the focus of the new analysis.

The average age of the 950 participants was 77 years; 61% were women. Two-thirds were hypertensive, 4% were current smokers, 49% drank three or more alcoholic drinks per week, and 6% had a history of stroke.

The researchers used three tests to evaluate cognitive function: the Mini-Mental State Exam (MMSE), which assessed features such as orientation, attention, and recall; the Trail-Making Test B, which gauged executive function; and a category fluency test that asked participants to name as many animals as they could in 1 minute.

The MMSE identified poor function in 7%, the trail-making test B identified poor function in 30%, and category fluency identified poor function in 15%.

Natriuretic peptide levels in the blood specimens were measured using a test that detects N-terminal pro-B-type natriuretic peptide (NT-proBNP). Natriuretic peptide measurements were considered low if the level was less than 450 pg/mL, and high if the level was 450 pg/mL or greater. Among the 950 participants, 79% had a low level and 21% had a high level.

People with high levels of NT-proBNP had significantly worse results in all three tests, compared with those who had low levels. In the low level group, poor cognitive scores occurred in 5%, 23%, and 12% of subjects for the three cognitive function tests, respectively. In the high level group, 17%, 54%, and 26% of the subjects scored poorly on the three tests, respectively.

When the results were adjusted for age, education, body mass index, exercise, alcohol use, and smoking, participants with high NT-proBNP levels had significantly worse cognitive function scores on the MMSE and the Trail-Making Test B. Poor scores for category fluency were lower in people with high NT-proBNP in the fully-adjusted model, but the difference fell short of statistical significance relative to those with low NT-proBNP.

Dr. Daniels received research support from Roche Diagnostics, which markets an NT-proBNP assay.

ORLANDO — A growing number of American children have increased left ventricular mass, a marker for cardiovascular disease risk.

The finding was noted in a study that included 700 children and “is the first study to look at average left ventricular mass in the whole pediatric population,” according to Dr. David I. Crowley, a pediatric cardiologist at Cincinnati Children's Hospital.

In children with an average age of 10 years, mean left ventricular mass rose by a statistically significant 4% from 1986 to 2008. The prevalence of left ventricular hypertrophy in the children more than doubled, from 7% to 15%, Dr. Crowley said at the annual scientific sessions of the American Heart Association.

The increase appears to be linked to obesity. In the 1986–1988 cohort of 350 children examined at Cincinnati Children's, the prevalence of overweight was 14% and of obesity was 5%.

In a matched cohort of 350 children assessed in 2008, the prevalence of overweight was 15% but the prevalence of obesity soared to 19%. Results from a multivariate analysis showed that body mass index was a major determinant of left ventricular mass, Dr. Crowley said.

The investigation included children aged 2–19 years. The participants came to Cincinnati Children's in 1986–1988 for an echocardiography examination because of a murmur, palpitations, syncope, or chest pain.

All 350 children included in the analysis had normal cardiac anatomy and function, and none had systemic disease or a body mass index of 40 kg/m

Dr. Crowley and his associates identified 350 children matched by age and gender who underwent echocardiography at their center during 2008 for similar reasons and met similar clinical criteria. Both cohorts were 60% boys, and 82% or 83% were white.

Analysis of the echocardiographic data showed that, in addition to having larger hearts, the more recently evaluated children also had a greater prevalence of high-risk cardiac morphology.

The prevalence of eccentric hypertrophy was 6% in the 1986–1988 group and 12% in the 2008 cohort. The prevalence of concentric hypertrophy also doubled in the more recent cohort.

Although average left ventricular mass rose by only 4% from the older to more contemporary cohort, this difference is important, commented Dr. Stephen R. Daniels.

“When you look at a population and a value gets worse by even a small amount, it suggests that many more in the population may now be in a high-risk category,” said Dr. Daniels, a pediatric cardiologist and professor and chairman of pediatrics at the University of Colorado in Denver.

Dr. Crowley had no financial disclosures for the study.

This 'is the first study to look at average left ventricular mass in the whole pediatric population.'

Source DR. CROWLEY

ORLANDO — A growing number of American children have increased left ventricular mass, a marker for cardiovascular disease risk.

The finding was noted in a study that included 700 children and “is the first study to look at average left ventricular mass in the whole pediatric population,” according to Dr. David I. Crowley, a pediatric cardiologist at Cincinnati Children's Hospital.

In children with an average age of 10 years, mean left ventricular mass rose by a statistically significant 4% from 1986 to 2008. The prevalence of left ventricular hypertrophy in the children more than doubled, from 7% to 15%, Dr. Crowley said at the annual scientific sessions of the American Heart Association.

The increase appears to be linked to obesity. In the 1986–1988 cohort of 350 children examined at Cincinnati Children's, the prevalence of overweight was 14% and of obesity was 5%.

In a matched cohort of 350 children assessed in 2008, the prevalence of overweight was 15% but the prevalence of obesity soared to 19%. Results from a multivariate analysis showed that body mass index was a major determinant of left ventricular mass, Dr. Crowley said.

The investigation included children aged 2–19 years. The participants came to Cincinnati Children's in 1986–1988 for an echocardiography examination because of a murmur, palpitations, syncope, or chest pain.

All 350 children included in the analysis had normal cardiac anatomy and function, and none had systemic disease or a body mass index of 40 kg/m

Dr. Crowley and his associates identified 350 children matched by age and gender who underwent echocardiography at their center during 2008 for similar reasons and met similar clinical criteria. Both cohorts were 60% boys, and 82% or 83% were white.

Analysis of the echocardiographic data showed that, in addition to having larger hearts, the more recently evaluated children also had a greater prevalence of high-risk cardiac morphology.

The prevalence of eccentric hypertrophy was 6% in the 1986–1988 group and 12% in the 2008 cohort. The prevalence of concentric hypertrophy also doubled in the more recent cohort.

Although average left ventricular mass rose by only 4% from the older to more contemporary cohort, this difference is important, commented Dr. Stephen R. Daniels.

“When you look at a population and a value gets worse by even a small amount, it suggests that many more in the population may now be in a high-risk category,” said Dr. Daniels, a pediatric cardiologist and professor and chairman of pediatrics at the University of Colorado in Denver.

Dr. Crowley had no financial disclosures for the study.

This 'is the first study to look at average left ventricular mass in the whole pediatric population.'

Source DR. CROWLEY

ORLANDO — A growing number of American children have increased left ventricular mass, a marker for cardiovascular disease risk.

The finding was noted in a study that included 700 children and “is the first study to look at average left ventricular mass in the whole pediatric population,” according to Dr. David I. Crowley, a pediatric cardiologist at Cincinnati Children's Hospital.

In children with an average age of 10 years, mean left ventricular mass rose by a statistically significant 4% from 1986 to 2008. The prevalence of left ventricular hypertrophy in the children more than doubled, from 7% to 15%, Dr. Crowley said at the annual scientific sessions of the American Heart Association.

The increase appears to be linked to obesity. In the 1986–1988 cohort of 350 children examined at Cincinnati Children's, the prevalence of overweight was 14% and of obesity was 5%.

In a matched cohort of 350 children assessed in 2008, the prevalence of overweight was 15% but the prevalence of obesity soared to 19%. Results from a multivariate analysis showed that body mass index was a major determinant of left ventricular mass, Dr. Crowley said.

The investigation included children aged 2–19 years. The participants came to Cincinnati Children's in 1986–1988 for an echocardiography examination because of a murmur, palpitations, syncope, or chest pain.

All 350 children included in the analysis had normal cardiac anatomy and function, and none had systemic disease or a body mass index of 40 kg/m

Dr. Crowley and his associates identified 350 children matched by age and gender who underwent echocardiography at their center during 2008 for similar reasons and met similar clinical criteria. Both cohorts were 60% boys, and 82% or 83% were white.

Analysis of the echocardiographic data showed that, in addition to having larger hearts, the more recently evaluated children also had a greater prevalence of high-risk cardiac morphology.

The prevalence of eccentric hypertrophy was 6% in the 1986–1988 group and 12% in the 2008 cohort. The prevalence of concentric hypertrophy also doubled in the more recent cohort.

Although average left ventricular mass rose by only 4% from the older to more contemporary cohort, this difference is important, commented Dr. Stephen R. Daniels.

“When you look at a population and a value gets worse by even a small amount, it suggests that many more in the population may now be in a high-risk category,” said Dr. Daniels, a pediatric cardiologist and professor and chairman of pediatrics at the University of Colorado in Denver.

Dr. Crowley had no financial disclosures for the study.

This 'is the first study to look at average left ventricular mass in the whole pediatric population.'

Source DR. CROWLEY