Heart Failure

BOSTON – Here’s heartening news that physicians can convey to breast cancer survivors: Modern breast irradiation did not appear to cause late-term cardiac toxicity in a study that examined women a quarter of a century after they were treated.

Investigators found no significant differences in Framingham Heart Study risk scores, hemodynamic parameters, pericardial thickening, or heart failure among 50 women who had been randomized in the 1970s and 1980s to either mastectomy or breast-conserving surgery (BCS) and radiation, Dr. Charles B. Simone II reported at the annual meeting of the American Society for Radiation Oncology.

Neil Osterweil/IMNG Medical Media

Although the survival rate was slightly lower among patients treated with breast-conserving therapy, the difference does not appear to be related to radiation dose to the heart, said Dr. Simone of the Hospital of the University of Pennsylvania in Philadelphia. There were no differences in survival among women treated with BCS and radiation to left- or right-sided tumors.

"Based on this study, in the era of 3D planning, patients with early-stage breast cancer treated with radiotherapy do not have a higher risk of long-term cardiac morbidity compared with patients having mastectomy," he said.

The patients studied included 50 of 102 survivors from an original cohort of 237 women who had participated in the National Cancer Institute’s Breast Conservation Trial (79-C-0111), with randomization from 1979 to 1986. In that trial, women with stage I or II breast cancer received modified radical mastectomy with axillary node dissection or they underwent lumpectomy plus node dissection and a radiation dose of 45-50.4 Gy to the whole breast; the latter came with or without treatment of regional nodes, followed by a boost of 15-20 Gy with either iridium 192 brachytherapy or electrons.

All node-positive patients underwent 6-11 cycles of chemotherapy with doxorubicin and cyclophosphamide, and beginning in 1985 postmenopausal women with positive nodes were given tamoxifen.

The trial was unique at the time in that it used CT simulations for treatment planning and dose inhomogeneity corrections, Dr. Simone noted.

Diverging Survival Curves

At a median of 25.7 years after randomization, 43.8% of mastectomy patients were still alive, compared with 37.9% of BCS patients. Although the difference was not significant, it appeared to represent a divergence of survival curves that had been virtually identical for the first 25 years.

The trend could not be accounted for by secondary malignancies, changes in distant metastasis, or any other breast cancer–related causes, leading the investigators to question whether it might be due to radiation toxicity to the heart, as some studies have suggested.

In all, 26 patients who had had BCS and 24 who underwent mastectomy agreed to come back for the cardiac toxicity study.

The investigators took a detailed cardiac history, and subjected the women to exams, cardiac labs, cardiac MRI with a 3 Tesla magnet to look for anatomic and functional abnormalities, and CT angiogram to look for stenotic coronary disease and determine coronary arterial calcium score (CAC) of atherosclerotic burden.

They also looked at radiation technique parameters such as central lung distance, field size, dose, and boost dose.

On cardiac MRI, they only saw two significant between-group differences. Time to peak filling rate was shorter for BCS patients (487 milliseconds vs. 647 ms for mastectomy patients; P = .02), but there was no difference in the peak filling rate itself. Left ventricular mass was smaller for BCS patients (mean 90.5 gm vs. 111 gm for mastectomy patients), but this difference was no longer significant after adjustment for systolic blood pressure, Dr. Simone noted.

"Interestingly, we didn’t see any evidence of myocardial fibrosis in any patient assessed, and only one patient in each arm had any degree of pericardial thickening," he said.

Reassuring Data

Additionally, investigators saw no significant differences on CT angiography in the presence of visible plaque or significant or severe vascular stenosis. There were also no differences in plaque or stenosis in the left anterior descending arteries of women treated with radiation for tumors on the left or the right side of the body.

"For each and every vessel we looked at, there was no difference in the degree of stenosis," Dr. Simone said.

Median CAC scores were low and in the normal range, but patients who had received chemotherapy had a trend toward increased atherosclerosis and plaque formation, Dr. Simone noted.

The study "gives some reassurance to our patients that, after 25 years of follow-up, using modern radiation techniques the delivery of radiation to the left does not cause cardiac toxicity," Dr. Bruce Haffty, chair of radiation oncology at the Cancer Institute of New Jersey, New Brunswick, said at a briefing.

The study was supported by the National Cancer Institute. Dr. Simone and Dr. Haffty reported no relevant disclosures.

BOSTON – Here’s heartening news that physicians can convey to breast cancer survivors: Modern breast irradiation did not appear to cause late-term cardiac toxicity in a study that examined women a quarter of a century after they were treated.

Investigators found no significant differences in Framingham Heart Study risk scores, hemodynamic parameters, pericardial thickening, or heart failure among 50 women who had been randomized in the 1970s and 1980s to either mastectomy or breast-conserving surgery (BCS) and radiation, Dr. Charles B. Simone II reported at the annual meeting of the American Society for Radiation Oncology.

Neil Osterweil/IMNG Medical Media

Although the survival rate was slightly lower among patients treated with breast-conserving therapy, the difference does not appear to be related to radiation dose to the heart, said Dr. Simone of the Hospital of the University of Pennsylvania in Philadelphia. There were no differences in survival among women treated with BCS and radiation to left- or right-sided tumors.

"Based on this study, in the era of 3D planning, patients with early-stage breast cancer treated with radiotherapy do not have a higher risk of long-term cardiac morbidity compared with patients having mastectomy," he said.

The patients studied included 50 of 102 survivors from an original cohort of 237 women who had participated in the National Cancer Institute’s Breast Conservation Trial (79-C-0111), with randomization from 1979 to 1986. In that trial, women with stage I or II breast cancer received modified radical mastectomy with axillary node dissection or they underwent lumpectomy plus node dissection and a radiation dose of 45-50.4 Gy to the whole breast; the latter came with or without treatment of regional nodes, followed by a boost of 15-20 Gy with either iridium 192 brachytherapy or electrons.

All node-positive patients underwent 6-11 cycles of chemotherapy with doxorubicin and cyclophosphamide, and beginning in 1985 postmenopausal women with positive nodes were given tamoxifen.

The trial was unique at the time in that it used CT simulations for treatment planning and dose inhomogeneity corrections, Dr. Simone noted.

Diverging Survival Curves

At a median of 25.7 years after randomization, 43.8% of mastectomy patients were still alive, compared with 37.9% of BCS patients. Although the difference was not significant, it appeared to represent a divergence of survival curves that had been virtually identical for the first 25 years.

The trend could not be accounted for by secondary malignancies, changes in distant metastasis, or any other breast cancer–related causes, leading the investigators to question whether it might be due to radiation toxicity to the heart, as some studies have suggested.

In all, 26 patients who had had BCS and 24 who underwent mastectomy agreed to come back for the cardiac toxicity study.

The investigators took a detailed cardiac history, and subjected the women to exams, cardiac labs, cardiac MRI with a 3 Tesla magnet to look for anatomic and functional abnormalities, and CT angiogram to look for stenotic coronary disease and determine coronary arterial calcium score (CAC) of atherosclerotic burden.

They also looked at radiation technique parameters such as central lung distance, field size, dose, and boost dose.

On cardiac MRI, they only saw two significant between-group differences. Time to peak filling rate was shorter for BCS patients (487 milliseconds vs. 647 ms for mastectomy patients; P = .02), but there was no difference in the peak filling rate itself. Left ventricular mass was smaller for BCS patients (mean 90.5 gm vs. 111 gm for mastectomy patients), but this difference was no longer significant after adjustment for systolic blood pressure, Dr. Simone noted.

"Interestingly, we didn’t see any evidence of myocardial fibrosis in any patient assessed, and only one patient in each arm had any degree of pericardial thickening," he said.

Reassuring Data

Additionally, investigators saw no significant differences on CT angiography in the presence of visible plaque or significant or severe vascular stenosis. There were also no differences in plaque or stenosis in the left anterior descending arteries of women treated with radiation for tumors on the left or the right side of the body.

"For each and every vessel we looked at, there was no difference in the degree of stenosis," Dr. Simone said.

Median CAC scores were low and in the normal range, but patients who had received chemotherapy had a trend toward increased atherosclerosis and plaque formation, Dr. Simone noted.

The study "gives some reassurance to our patients that, after 25 years of follow-up, using modern radiation techniques the delivery of radiation to the left does not cause cardiac toxicity," Dr. Bruce Haffty, chair of radiation oncology at the Cancer Institute of New Jersey, New Brunswick, said at a briefing.

The study was supported by the National Cancer Institute. Dr. Simone and Dr. Haffty reported no relevant disclosures.

BOSTON – Here’s heartening news that physicians can convey to breast cancer survivors: Modern breast irradiation did not appear to cause late-term cardiac toxicity in a study that examined women a quarter of a century after they were treated.

Investigators found no significant differences in Framingham Heart Study risk scores, hemodynamic parameters, pericardial thickening, or heart failure among 50 women who had been randomized in the 1970s and 1980s to either mastectomy or breast-conserving surgery (BCS) and radiation, Dr. Charles B. Simone II reported at the annual meeting of the American Society for Radiation Oncology.

Neil Osterweil/IMNG Medical Media

Although the survival rate was slightly lower among patients treated with breast-conserving therapy, the difference does not appear to be related to radiation dose to the heart, said Dr. Simone of the Hospital of the University of Pennsylvania in Philadelphia. There were no differences in survival among women treated with BCS and radiation to left- or right-sided tumors.

"Based on this study, in the era of 3D planning, patients with early-stage breast cancer treated with radiotherapy do not have a higher risk of long-term cardiac morbidity compared with patients having mastectomy," he said.

The patients studied included 50 of 102 survivors from an original cohort of 237 women who had participated in the National Cancer Institute’s Breast Conservation Trial (79-C-0111), with randomization from 1979 to 1986. In that trial, women with stage I or II breast cancer received modified radical mastectomy with axillary node dissection or they underwent lumpectomy plus node dissection and a radiation dose of 45-50.4 Gy to the whole breast; the latter came with or without treatment of regional nodes, followed by a boost of 15-20 Gy with either iridium 192 brachytherapy or electrons.

All node-positive patients underwent 6-11 cycles of chemotherapy with doxorubicin and cyclophosphamide, and beginning in 1985 postmenopausal women with positive nodes were given tamoxifen.

The trial was unique at the time in that it used CT simulations for treatment planning and dose inhomogeneity corrections, Dr. Simone noted.

Diverging Survival Curves

At a median of 25.7 years after randomization, 43.8% of mastectomy patients were still alive, compared with 37.9% of BCS patients. Although the difference was not significant, it appeared to represent a divergence of survival curves that had been virtually identical for the first 25 years.

The trend could not be accounted for by secondary malignancies, changes in distant metastasis, or any other breast cancer–related causes, leading the investigators to question whether it might be due to radiation toxicity to the heart, as some studies have suggested.

In all, 26 patients who had had BCS and 24 who underwent mastectomy agreed to come back for the cardiac toxicity study.

The investigators took a detailed cardiac history, and subjected the women to exams, cardiac labs, cardiac MRI with a 3 Tesla magnet to look for anatomic and functional abnormalities, and CT angiogram to look for stenotic coronary disease and determine coronary arterial calcium score (CAC) of atherosclerotic burden.

They also looked at radiation technique parameters such as central lung distance, field size, dose, and boost dose.

On cardiac MRI, they only saw two significant between-group differences. Time to peak filling rate was shorter for BCS patients (487 milliseconds vs. 647 ms for mastectomy patients; P = .02), but there was no difference in the peak filling rate itself. Left ventricular mass was smaller for BCS patients (mean 90.5 gm vs. 111 gm for mastectomy patients), but this difference was no longer significant after adjustment for systolic blood pressure, Dr. Simone noted.

"Interestingly, we didn’t see any evidence of myocardial fibrosis in any patient assessed, and only one patient in each arm had any degree of pericardial thickening," he said.

Reassuring Data

Additionally, investigators saw no significant differences on CT angiography in the presence of visible plaque or significant or severe vascular stenosis. There were also no differences in plaque or stenosis in the left anterior descending arteries of women treated with radiation for tumors on the left or the right side of the body.

"For each and every vessel we looked at, there was no difference in the degree of stenosis," Dr. Simone said.

Median CAC scores were low and in the normal range, but patients who had received chemotherapy had a trend toward increased atherosclerosis and plaque formation, Dr. Simone noted.

The study "gives some reassurance to our patients that, after 25 years of follow-up, using modern radiation techniques the delivery of radiation to the left does not cause cardiac toxicity," Dr. Bruce Haffty, chair of radiation oncology at the Cancer Institute of New Jersey, New Brunswick, said at a briefing.

The study was supported by the National Cancer Institute. Dr. Simone and Dr. Haffty reported no relevant disclosures.

MUNICH – Results from the largest study to ever assess treatment with spironolactone in patients with diastolic heart failure showed clear indications that the drug exerted beneficial structural, hemodynamic, and physiologic effects with a generally reasonable safety profile.

But the mottled results also showed a puzzling lack of efficacy for other end points, and when coupled with some worrisome signs of harm, most physicians will probably reserve judgment on using spironolactone on patients with heart failure and preserved left ventricular ejection fraction until results from an even larger, clinical end point trial are available next year.

Mitchel L. Zoler/IMNG Medical Media

Based on the results, "spironolactone can be considered in patients with diastolic heart failure for improving cardiac function and blood pressure control," Dr. Burkert M. Pieske said at the annual congress of the European Society of Cardiology.

Moreover, spironolactone’s performance in the Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) trial with 422 patients randomized to treatment with spironolactone or placebo gives the drug a unique position in the world of diastolic heart failure: Spironolactone is now the only drug with any sort of positive track record in a prospective controlled trial.

"I can’t give a general recommendation to use it because patients [on spironolactone in the trial] did not feel better" after a year on treatment, Dr. Pieske acknowledged in an interview. "But if I had a [diastolic heart failure] patient on dual or triple antihypertensive therapy who still had high blood pressure, I would not hesitate to put the patient on spironolactone if their renal function and potassium level allowed it. This treatment will reduce blood pressure and improve cardiac structure and function," said Dr. Pieske, professor and head of the department of cardiology at the Medical University of Graz, Austria.

But other experts who heard the results had doubts.

"It was not all good news. Patients had an increase in their potassium level, and even more concerning, they had a reduction in their glomerular filtration rate, an average reduction of about 5 mL/min," commented Dr. Stefan D. Anker, professor of medicine at Charité Medical University in Berlin. In addition, the distance walked on the 6-minute walk test was "slightly decreased with spironolactone. Even though it was a small change of 15 m, it was statistically significant," he noted. On top of all this, "worsening of anemia was seen in patients," he added.

Dr. Anker advised waiting for results that are expected to come out next year from TOPCAT, a U.S. study of spironolactone in more than 3,500 patients with diastolic heart failure sponsored by the National Heart, Lung, and Blood Institute.

Aldo-CHF enrolled patients aged 50 years or older with New York Heart Association class II or III heart failure and a left ventricular ejection fraction of at least 50%. Patients also needed to have echocardiographic evidence of diastolic dysfunction, and a peak oxygen consumption (VO₂) of less than 25 mL/kg per minute. The study excluded patients with a serum potassium level of 5.1 mmol/L or higher, and those with an estimated glomerular filtration rate of less than 30 mL/min per 1.73 m² or a serum creatinine greater than 1.8 mg/dL. The patients averaged 67 years old, about 86% had class II heart failure, their average ejection fraction was about 67%, and their average GFR was about 79 mL/min per 1.73 m².

The researchers randomized 213 patients to received 25 mg of spironolactone daily, and 209 control patients to placebo. Patients also received other medications, with about three-quarters on an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, about three-quarters receiving a beta-blocker, and slightly more than half receiving a diuretic.

The study had two primary end points. After 12 months, patients on spironolactone had an average reduction in the E/é ratio of 0.6 (a 5% drop from baseline), compared with an average rise among the control patients of 0.8 (a 6% rise from baseline) for this surrogate measure of filling pressure, a significant between-group difference. The second primary end point was change in peak VO₂, and for this measure the two groups showed very similar changes over the 12 months of the study without a significant between-group difference.

Patients on spironolactone also had a significant reduction in average blood pressure of 8/2 mm Hg at 12 months compared with baseline, but the beneficial effect that spironolactone had on myocardial reverse remodeling reflected in the change in E/é occurred independent of the drug’s blood pressure effect, Dr. Pieske said.

Secondary end points that showed beneficial effects from spironolactone treatment included a small but significant increase in left ventricular ejection fraction, and a significant reduction in serum levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP), a marker of heart failure severity. But patients on spironolactone also had an average 15-m reduction in their 6-minute walk distance, a significant drop.

"We saw consistent structural and functional remodeling effects from spironolactone, and except for left ventricular size, all of the other measures improved. But we saw no benefit on exercise capacity, New York Heart Association class, or quality of life," Dr. Pieske said. "Somehow, the beneficial effects on the heart did not translate into an improved situation."

While the overall safety profile of spironolactone treatment was good, the results showed a few possible areas of concern. In the spironolactone group, 36% of patients had worsening renal function, compared with 21% in the control arm, a significant difference; and the average GFR fell by about 7 mL/min per 1.73 m² with spironolactone, compared with no change in the control patients. The incidence of new or worsening anemia was 16% among the spironolactone patients and 9% in the controls, a significant difference. And twice as many patients on spironolactone had an increase in their serum potassium compared with the controls. However, the incidence of severe hyperkalemia was low and similar in both arms of the study.

"To our knowledge, increased anemia was not seen before" with spironolactone. "Maybe the anemia or a mild decrease in hemoglobin contributed" to the lack of an effect of treatment on exercise capacity, Dr. Pieske suggested.

Aldo-DHF was sponsored by the German government. Dr. Pieske said that he and his associates had no disclosures. Dr. Anker said that he has received consulting fees from Amgen, Bosch Healthcare, and other companies.

MUNICH – Results from the largest study to ever assess treatment with spironolactone in patients with diastolic heart failure showed clear indications that the drug exerted beneficial structural, hemodynamic, and physiologic effects with a generally reasonable safety profile.

But the mottled results also showed a puzzling lack of efficacy for other end points, and when coupled with some worrisome signs of harm, most physicians will probably reserve judgment on using spironolactone on patients with heart failure and preserved left ventricular ejection fraction until results from an even larger, clinical end point trial are available next year.

Mitchel L. Zoler/IMNG Medical Media

Based on the results, "spironolactone can be considered in patients with diastolic heart failure for improving cardiac function and blood pressure control," Dr. Burkert M. Pieske said at the annual congress of the European Society of Cardiology.

Moreover, spironolactone’s performance in the Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) trial with 422 patients randomized to treatment with spironolactone or placebo gives the drug a unique position in the world of diastolic heart failure: Spironolactone is now the only drug with any sort of positive track record in a prospective controlled trial.

"I can’t give a general recommendation to use it because patients [on spironolactone in the trial] did not feel better" after a year on treatment, Dr. Pieske acknowledged in an interview. "But if I had a [diastolic heart failure] patient on dual or triple antihypertensive therapy who still had high blood pressure, I would not hesitate to put the patient on spironolactone if their renal function and potassium level allowed it. This treatment will reduce blood pressure and improve cardiac structure and function," said Dr. Pieske, professor and head of the department of cardiology at the Medical University of Graz, Austria.

But other experts who heard the results had doubts.

"It was not all good news. Patients had an increase in their potassium level, and even more concerning, they had a reduction in their glomerular filtration rate, an average reduction of about 5 mL/min," commented Dr. Stefan D. Anker, professor of medicine at Charité Medical University in Berlin. In addition, the distance walked on the 6-minute walk test was "slightly decreased with spironolactone. Even though it was a small change of 15 m, it was statistically significant," he noted. On top of all this, "worsening of anemia was seen in patients," he added.

Dr. Anker advised waiting for results that are expected to come out next year from TOPCAT, a U.S. study of spironolactone in more than 3,500 patients with diastolic heart failure sponsored by the National Heart, Lung, and Blood Institute.

Aldo-CHF enrolled patients aged 50 years or older with New York Heart Association class II or III heart failure and a left ventricular ejection fraction of at least 50%. Patients also needed to have echocardiographic evidence of diastolic dysfunction, and a peak oxygen consumption (VO₂) of less than 25 mL/kg per minute. The study excluded patients with a serum potassium level of 5.1 mmol/L or higher, and those with an estimated glomerular filtration rate of less than 30 mL/min per 1.73 m² or a serum creatinine greater than 1.8 mg/dL. The patients averaged 67 years old, about 86% had class II heart failure, their average ejection fraction was about 67%, and their average GFR was about 79 mL/min per 1.73 m².

The researchers randomized 213 patients to received 25 mg of spironolactone daily, and 209 control patients to placebo. Patients also received other medications, with about three-quarters on an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, about three-quarters receiving a beta-blocker, and slightly more than half receiving a diuretic.

The study had two primary end points. After 12 months, patients on spironolactone had an average reduction in the E/é ratio of 0.6 (a 5% drop from baseline), compared with an average rise among the control patients of 0.8 (a 6% rise from baseline) for this surrogate measure of filling pressure, a significant between-group difference. The second primary end point was change in peak VO₂, and for this measure the two groups showed very similar changes over the 12 months of the study without a significant between-group difference.

Patients on spironolactone also had a significant reduction in average blood pressure of 8/2 mm Hg at 12 months compared with baseline, but the beneficial effect that spironolactone had on myocardial reverse remodeling reflected in the change in E/é occurred independent of the drug’s blood pressure effect, Dr. Pieske said.

Secondary end points that showed beneficial effects from spironolactone treatment included a small but significant increase in left ventricular ejection fraction, and a significant reduction in serum levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP), a marker of heart failure severity. But patients on spironolactone also had an average 15-m reduction in their 6-minute walk distance, a significant drop.

"We saw consistent structural and functional remodeling effects from spironolactone, and except for left ventricular size, all of the other measures improved. But we saw no benefit on exercise capacity, New York Heart Association class, or quality of life," Dr. Pieske said. "Somehow, the beneficial effects on the heart did not translate into an improved situation."

While the overall safety profile of spironolactone treatment was good, the results showed a few possible areas of concern. In the spironolactone group, 36% of patients had worsening renal function, compared with 21% in the control arm, a significant difference; and the average GFR fell by about 7 mL/min per 1.73 m² with spironolactone, compared with no change in the control patients. The incidence of new or worsening anemia was 16% among the spironolactone patients and 9% in the controls, a significant difference. And twice as many patients on spironolactone had an increase in their serum potassium compared with the controls. However, the incidence of severe hyperkalemia was low and similar in both arms of the study.

"To our knowledge, increased anemia was not seen before" with spironolactone. "Maybe the anemia or a mild decrease in hemoglobin contributed" to the lack of an effect of treatment on exercise capacity, Dr. Pieske suggested.

Aldo-DHF was sponsored by the German government. Dr. Pieske said that he and his associates had no disclosures. Dr. Anker said that he has received consulting fees from Amgen, Bosch Healthcare, and other companies.

MUNICH – Results from the largest study to ever assess treatment with spironolactone in patients with diastolic heart failure showed clear indications that the drug exerted beneficial structural, hemodynamic, and physiologic effects with a generally reasonable safety profile.

But the mottled results also showed a puzzling lack of efficacy for other end points, and when coupled with some worrisome signs of harm, most physicians will probably reserve judgment on using spironolactone on patients with heart failure and preserved left ventricular ejection fraction until results from an even larger, clinical end point trial are available next year.

Mitchel L. Zoler/IMNG Medical Media

Based on the results, "spironolactone can be considered in patients with diastolic heart failure for improving cardiac function and blood pressure control," Dr. Burkert M. Pieske said at the annual congress of the European Society of Cardiology.

Moreover, spironolactone’s performance in the Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) trial with 422 patients randomized to treatment with spironolactone or placebo gives the drug a unique position in the world of diastolic heart failure: Spironolactone is now the only drug with any sort of positive track record in a prospective controlled trial.

"I can’t give a general recommendation to use it because patients [on spironolactone in the trial] did not feel better" after a year on treatment, Dr. Pieske acknowledged in an interview. "But if I had a [diastolic heart failure] patient on dual or triple antihypertensive therapy who still had high blood pressure, I would not hesitate to put the patient on spironolactone if their renal function and potassium level allowed it. This treatment will reduce blood pressure and improve cardiac structure and function," said Dr. Pieske, professor and head of the department of cardiology at the Medical University of Graz, Austria.

But other experts who heard the results had doubts.

"It was not all good news. Patients had an increase in their potassium level, and even more concerning, they had a reduction in their glomerular filtration rate, an average reduction of about 5 mL/min," commented Dr. Stefan D. Anker, professor of medicine at Charité Medical University in Berlin. In addition, the distance walked on the 6-minute walk test was "slightly decreased with spironolactone. Even though it was a small change of 15 m, it was statistically significant," he noted. On top of all this, "worsening of anemia was seen in patients," he added.

Dr. Anker advised waiting for results that are expected to come out next year from TOPCAT, a U.S. study of spironolactone in more than 3,500 patients with diastolic heart failure sponsored by the National Heart, Lung, and Blood Institute.

Aldo-CHF enrolled patients aged 50 years or older with New York Heart Association class II or III heart failure and a left ventricular ejection fraction of at least 50%. Patients also needed to have echocardiographic evidence of diastolic dysfunction, and a peak oxygen consumption (VO₂) of less than 25 mL/kg per minute. The study excluded patients with a serum potassium level of 5.1 mmol/L or higher, and those with an estimated glomerular filtration rate of less than 30 mL/min per 1.73 m² or a serum creatinine greater than 1.8 mg/dL. The patients averaged 67 years old, about 86% had class II heart failure, their average ejection fraction was about 67%, and their average GFR was about 79 mL/min per 1.73 m².

The researchers randomized 213 patients to received 25 mg of spironolactone daily, and 209 control patients to placebo. Patients also received other medications, with about three-quarters on an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, about three-quarters receiving a beta-blocker, and slightly more than half receiving a diuretic.

The study had two primary end points. After 12 months, patients on spironolactone had an average reduction in the E/é ratio of 0.6 (a 5% drop from baseline), compared with an average rise among the control patients of 0.8 (a 6% rise from baseline) for this surrogate measure of filling pressure, a significant between-group difference. The second primary end point was change in peak VO₂, and for this measure the two groups showed very similar changes over the 12 months of the study without a significant between-group difference.

Patients on spironolactone also had a significant reduction in average blood pressure of 8/2 mm Hg at 12 months compared with baseline, but the beneficial effect that spironolactone had on myocardial reverse remodeling reflected in the change in E/é occurred independent of the drug’s blood pressure effect, Dr. Pieske said.

Secondary end points that showed beneficial effects from spironolactone treatment included a small but significant increase in left ventricular ejection fraction, and a significant reduction in serum levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP), a marker of heart failure severity. But patients on spironolactone also had an average 15-m reduction in their 6-minute walk distance, a significant drop.

"We saw consistent structural and functional remodeling effects from spironolactone, and except for left ventricular size, all of the other measures improved. But we saw no benefit on exercise capacity, New York Heart Association class, or quality of life," Dr. Pieske said. "Somehow, the beneficial effects on the heart did not translate into an improved situation."

While the overall safety profile of spironolactone treatment was good, the results showed a few possible areas of concern. In the spironolactone group, 36% of patients had worsening renal function, compared with 21% in the control arm, a significant difference; and the average GFR fell by about 7 mL/min per 1.73 m² with spironolactone, compared with no change in the control patients. The incidence of new or worsening anemia was 16% among the spironolactone patients and 9% in the controls, a significant difference. And twice as many patients on spironolactone had an increase in their serum potassium compared with the controls. However, the incidence of severe hyperkalemia was low and similar in both arms of the study.

"To our knowledge, increased anemia was not seen before" with spironolactone. "Maybe the anemia or a mild decrease in hemoglobin contributed" to the lack of an effect of treatment on exercise capacity, Dr. Pieske suggested.

Aldo-DHF was sponsored by the German government. Dr. Pieske said that he and his associates had no disclosures. Dr. Anker said that he has received consulting fees from Amgen, Bosch Healthcare, and other companies.

SEATTLE – Aldosterone antagonists can be used safely and effectively to treat heart failure in real-world practice, and their underuse likely accounts for a sizable share of deaths in this patient population, according to Dr. Gregg C. Fonarow, cochief of the division of cardiology at the University of California, Los Angeles.

These agents are among six heart failure therapies having a class I (highest) recommendation in national guidelines for managing heart failure, he said at the annual meeting of the Heart Failure Society of America. Yet, nearly 68,000 patients with heart failure and reduced left ventricular ejection fraction (LVEF) die each year in the United States because they do not receive these therapies (Am. Heart J. 2011;161:1024-30).

"If we bridged that gap, and assuming the efficacy and effectiveness match, you can see the potential number of lives saved each year. ... And, in fact, the greatest number of lives saved [roughly 21,400] could result from the improved use of aldosterone antagonists, if there were optimal implementation," he said.

Indeed, analyses show that only about one-third of eligible heart failure outpatients (Circ. Heart Fail. 2008;1:98-106) and inpatients (JAMA 2009;302:1658-65) in real-world U.S. practice receive drugs in this class.

Some resistance to the use of aldosterone antagonists – such as spironolactone (brand name Aldactone) and eplerenone (Inspra) – has stemmed from uncertainty as to whether the risk-benefit profile in clinical trials translates to real-world practice, according to Dr. Fonarow.

A recent analysis suggests that among patients with heart failure and reduced LVEF, aldosterone antagonist therapy decreases the risk of death by about 30% and the risk of hospitalization by 35% (Am. Heart J. 2011;161:1024-30). The number needed to treat to prevent a single death in a 36-month period is just eight, and the benefit is incremental to that of other standard therapies.

"There was just a moderate increase in the risk of hyperkalemia and increased creatinine, but overall, safe and well tolerated," he said. "They were shown to be highly cost effective even with fully branded medications at full cost, and the benefits greatly outweighed the potential risks."

However, an analysis of Canadian administrative data showed that after publication of the Randomized Aldactone Evaluation Study (RALES), which found significant benefit of spironolactone in heart failure, there was an increase in prescriptions for the drug but also a concomitant increase in hyperkalemia-related hospitalizations and deaths (N. Engl. J. Med. 2004;351:543-51).

The analysis did not assess benefits and had some limitations, according to Dr. Fonarow. "But after that publication and a few others, a number of notable heart failure experts stated pretty strong viewpoints that aldosterone antagonists are really not safe in real-world clinical practice, the risks outweigh any potential benefits, and they should be reserved only for the most severe heart failure patients and only after all other therapies have been tried and failed."

Yet, other studies have suggested, for example, that every 10% increase in aldosterone antagonist use among hospitalized patients is associated with a 6% reduction in all-cause mortality over the following year (Am. Heart J. 2010;159:406-13). Furthermore, in the context of careful monitoring, with increasing use of spironolactone, hyperkalemia is not problematic (BMJ 2010;340:c1768).

"Certainly, some of the data have had a number of individuals saying, ‘We need to get away from evidence guidelines and performance measures, and individualize therapy,’ and ‘I should pick and choose therapy as I think,’ and ‘Findings from clinical trials are not applicable to my patients, they are much more complex, and I know my patients are going to do well because I give them highly personalized care rather than cookbook medicine,’" Dr. Fonarow commented. "That is certainly not a very scientific or satisfying type of approach."

Experience from IMPROVE HF suggests that a performance improvement program can safely and effectively increase the use of aldosterone antagonists for heart failure in a real-world setting (Circulation 2010;122:585-96). The program led to a near doubling of use of these agents over 2 years. "At the same time, did we see any increase in inappropriate or ineligible patients being treated? No, the rates for patients with absolute contraindications or relative contraindications was very small, below 1%, and did not increase," he said.

"Treatment gaps between guidelines and practice exist for heart failure and, as a result, large numbers of patients are having hospitalizations and fatal events that could have been prevented. This is particularly true for aldosterone antagonists," Dr. Fonarow concluded. "Bridging the gap between evidence and clinical practice systems is needed, and by applying these evidence-based therapies with the appropriate monitoring and the appropriate selection of patients, we can do this in a way that truly will improve outcomes."

Dr. Fonarow disclosed that he is a consultant to and/or receives honoraria or research funding from Novartis and Medtronic.

SEATTLE – Aldosterone antagonists can be used safely and effectively to treat heart failure in real-world practice, and their underuse likely accounts for a sizable share of deaths in this patient population, according to Dr. Gregg C. Fonarow, cochief of the division of cardiology at the University of California, Los Angeles.

These agents are among six heart failure therapies having a class I (highest) recommendation in national guidelines for managing heart failure, he said at the annual meeting of the Heart Failure Society of America. Yet, nearly 68,000 patients with heart failure and reduced left ventricular ejection fraction (LVEF) die each year in the United States because they do not receive these therapies (Am. Heart J. 2011;161:1024-30).

"If we bridged that gap, and assuming the efficacy and effectiveness match, you can see the potential number of lives saved each year. ... And, in fact, the greatest number of lives saved [roughly 21,400] could result from the improved use of aldosterone antagonists, if there were optimal implementation," he said.

Indeed, analyses show that only about one-third of eligible heart failure outpatients (Circ. Heart Fail. 2008;1:98-106) and inpatients (JAMA 2009;302:1658-65) in real-world U.S. practice receive drugs in this class.

Some resistance to the use of aldosterone antagonists – such as spironolactone (brand name Aldactone) and eplerenone (Inspra) – has stemmed from uncertainty as to whether the risk-benefit profile in clinical trials translates to real-world practice, according to Dr. Fonarow.

A recent analysis suggests that among patients with heart failure and reduced LVEF, aldosterone antagonist therapy decreases the risk of death by about 30% and the risk of hospitalization by 35% (Am. Heart J. 2011;161:1024-30). The number needed to treat to prevent a single death in a 36-month period is just eight, and the benefit is incremental to that of other standard therapies.

"There was just a moderate increase in the risk of hyperkalemia and increased creatinine, but overall, safe and well tolerated," he said. "They were shown to be highly cost effective even with fully branded medications at full cost, and the benefits greatly outweighed the potential risks."

However, an analysis of Canadian administrative data showed that after publication of the Randomized Aldactone Evaluation Study (RALES), which found significant benefit of spironolactone in heart failure, there was an increase in prescriptions for the drug but also a concomitant increase in hyperkalemia-related hospitalizations and deaths (N. Engl. J. Med. 2004;351:543-51).

The analysis did not assess benefits and had some limitations, according to Dr. Fonarow. "But after that publication and a few others, a number of notable heart failure experts stated pretty strong viewpoints that aldosterone antagonists are really not safe in real-world clinical practice, the risks outweigh any potential benefits, and they should be reserved only for the most severe heart failure patients and only after all other therapies have been tried and failed."

Yet, other studies have suggested, for example, that every 10% increase in aldosterone antagonist use among hospitalized patients is associated with a 6% reduction in all-cause mortality over the following year (Am. Heart J. 2010;159:406-13). Furthermore, in the context of careful monitoring, with increasing use of spironolactone, hyperkalemia is not problematic (BMJ 2010;340:c1768).

"Certainly, some of the data have had a number of individuals saying, ‘We need to get away from evidence guidelines and performance measures, and individualize therapy,’ and ‘I should pick and choose therapy as I think,’ and ‘Findings from clinical trials are not applicable to my patients, they are much more complex, and I know my patients are going to do well because I give them highly personalized care rather than cookbook medicine,’" Dr. Fonarow commented. "That is certainly not a very scientific or satisfying type of approach."

Experience from IMPROVE HF suggests that a performance improvement program can safely and effectively increase the use of aldosterone antagonists for heart failure in a real-world setting (Circulation 2010;122:585-96). The program led to a near doubling of use of these agents over 2 years. "At the same time, did we see any increase in inappropriate or ineligible patients being treated? No, the rates for patients with absolute contraindications or relative contraindications was very small, below 1%, and did not increase," he said.

"Treatment gaps between guidelines and practice exist for heart failure and, as a result, large numbers of patients are having hospitalizations and fatal events that could have been prevented. This is particularly true for aldosterone antagonists," Dr. Fonarow concluded. "Bridging the gap between evidence and clinical practice systems is needed, and by applying these evidence-based therapies with the appropriate monitoring and the appropriate selection of patients, we can do this in a way that truly will improve outcomes."

Dr. Fonarow disclosed that he is a consultant to and/or receives honoraria or research funding from Novartis and Medtronic.

SEATTLE – Aldosterone antagonists can be used safely and effectively to treat heart failure in real-world practice, and their underuse likely accounts for a sizable share of deaths in this patient population, according to Dr. Gregg C. Fonarow, cochief of the division of cardiology at the University of California, Los Angeles.

These agents are among six heart failure therapies having a class I (highest) recommendation in national guidelines for managing heart failure, he said at the annual meeting of the Heart Failure Society of America. Yet, nearly 68,000 patients with heart failure and reduced left ventricular ejection fraction (LVEF) die each year in the United States because they do not receive these therapies (Am. Heart J. 2011;161:1024-30).

"If we bridged that gap, and assuming the efficacy and effectiveness match, you can see the potential number of lives saved each year. ... And, in fact, the greatest number of lives saved [roughly 21,400] could result from the improved use of aldosterone antagonists, if there were optimal implementation," he said.

Indeed, analyses show that only about one-third of eligible heart failure outpatients (Circ. Heart Fail. 2008;1:98-106) and inpatients (JAMA 2009;302:1658-65) in real-world U.S. practice receive drugs in this class.

Some resistance to the use of aldosterone antagonists – such as spironolactone (brand name Aldactone) and eplerenone (Inspra) – has stemmed from uncertainty as to whether the risk-benefit profile in clinical trials translates to real-world practice, according to Dr. Fonarow.

A recent analysis suggests that among patients with heart failure and reduced LVEF, aldosterone antagonist therapy decreases the risk of death by about 30% and the risk of hospitalization by 35% (Am. Heart J. 2011;161:1024-30). The number needed to treat to prevent a single death in a 36-month period is just eight, and the benefit is incremental to that of other standard therapies.

"There was just a moderate increase in the risk of hyperkalemia and increased creatinine, but overall, safe and well tolerated," he said. "They were shown to be highly cost effective even with fully branded medications at full cost, and the benefits greatly outweighed the potential risks."

However, an analysis of Canadian administrative data showed that after publication of the Randomized Aldactone Evaluation Study (RALES), which found significant benefit of spironolactone in heart failure, there was an increase in prescriptions for the drug but also a concomitant increase in hyperkalemia-related hospitalizations and deaths (N. Engl. J. Med. 2004;351:543-51).

The analysis did not assess benefits and had some limitations, according to Dr. Fonarow. "But after that publication and a few others, a number of notable heart failure experts stated pretty strong viewpoints that aldosterone antagonists are really not safe in real-world clinical practice, the risks outweigh any potential benefits, and they should be reserved only for the most severe heart failure patients and only after all other therapies have been tried and failed."

Yet, other studies have suggested, for example, that every 10% increase in aldosterone antagonist use among hospitalized patients is associated with a 6% reduction in all-cause mortality over the following year (Am. Heart J. 2010;159:406-13). Furthermore, in the context of careful monitoring, with increasing use of spironolactone, hyperkalemia is not problematic (BMJ 2010;340:c1768).

"Certainly, some of the data have had a number of individuals saying, ‘We need to get away from evidence guidelines and performance measures, and individualize therapy,’ and ‘I should pick and choose therapy as I think,’ and ‘Findings from clinical trials are not applicable to my patients, they are much more complex, and I know my patients are going to do well because I give them highly personalized care rather than cookbook medicine,’" Dr. Fonarow commented. "That is certainly not a very scientific or satisfying type of approach."

Experience from IMPROVE HF suggests that a performance improvement program can safely and effectively increase the use of aldosterone antagonists for heart failure in a real-world setting (Circulation 2010;122:585-96). The program led to a near doubling of use of these agents over 2 years. "At the same time, did we see any increase in inappropriate or ineligible patients being treated? No, the rates for patients with absolute contraindications or relative contraindications was very small, below 1%, and did not increase," he said.

"Treatment gaps between guidelines and practice exist for heart failure and, as a result, large numbers of patients are having hospitalizations and fatal events that could have been prevented. This is particularly true for aldosterone antagonists," Dr. Fonarow concluded. "Bridging the gap between evidence and clinical practice systems is needed, and by applying these evidence-based therapies with the appropriate monitoring and the appropriate selection of patients, we can do this in a way that truly will improve outcomes."

Dr. Fonarow disclosed that he is a consultant to and/or receives honoraria or research funding from Novartis and Medtronic.

MUNICH – Gender differences in comorbidities affected the medications prescribed to men and women hospitalized with acute heart failure, although their in-hospital mortality rate remained similar, according to a retrospective analysis of nearly 5,000 hospital charts.

The study showed that men who were hospitalized with acute heart failure (AHF) were more likely to receive beta-blockers and aspirin than were women. Meanwhile, women were more likely to be obese, have diabetes, or have atrial fibrillation.

"Perhaps there are differences in the pathophysiology of AHF between women and men, which should be taken into account in order to achieve gender-tailored management," said Dr. John Parissis, who presented the study at the annual congress of the European Society of Cardiology.

The study was a subanalysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF), a chart audit survey of 4,953 patients hospitalized for AHF in 666 hospitals in nine countries (France, Germany, Spain, Italy, Greece, United Kingdom, Turkey, Australia, and Mexico.)

Women made up 37% of the patients, consistent with ratios in other registries, said Dr. Parissis of Attikon University Hospital, Greece. They presented with AHF at an older age and had higher rates of de novo heart failure. They were also half as likely as were men to present with cardiogenic shock, but more than twice as likely to have right heart failure.

The study showed that women hospitalized with AHF had a higher prevalence of diabetes (47% v. 43%), obesity (30% v. 25%), anemia (17% v. 13%), atrial fibrillation or flutter (49% v. 42%), dementia (6% v. 3%), and depression (11% v. 7%), compared with men.

Meanwhile, men had a higher prevalence of chronic obstructive pulmonary disease (COPD) and asthma (27% v. 21%), and coronary artery disease (CAD) (35% v. 24%) compared with women.

Upon admission, women were less likely than were men to receive aspirin, clopidogrel, and beta-blockers, because of their comorbidities and lower rates of CAD. But compared with men, they were more likely to be on angiotensin receptors blockers and digitalis treatment, because of higher incidence of atrial fibrillation, according to the investigators.

There were no significant differences in use of ACE inhibitors, diuretics, and nitrates between genders, the analysis showed.

Both genders received continuous positive airway pressure (CPAP) and mechanical ventilation. Fewer women, however, were supported by intra-aortic balloon pump (IABP), underwent percutaneous coronary intervention, or had coronary artery bypass graft surgery.

In addition, in-hospital mortality was similar between genders (10.5% for men vs 11.1% for women). "The presence of higher ejection fraction and less CAD in women may positively affect survival in women," said Dr. Parissis.

But, "the existence of other serious comorbidities and underprescription of life saving medications such as beta-blockers may counteract this positive effect on their in-hospital survival," he added. "This point may explain the similar mortality rate between genders."

At discharge, the proportion of patients treated with medications increased. Nevertheless, the differences between genders remained significant, the authors wrote.

The differences in treatment call for "a more intensive implementation of heart failure guidelines to optimize life saving medications, especially in women," said Dr. Parissis.

Dr. Parissis is a member of the ALARM-HF Steering Committee and presented the study on the committee’s behalf. He said he had received research grants from Abbott and Orion Pharma.

MUNICH – Gender differences in comorbidities affected the medications prescribed to men and women hospitalized with acute heart failure, although their in-hospital mortality rate remained similar, according to a retrospective analysis of nearly 5,000 hospital charts.

The study showed that men who were hospitalized with acute heart failure (AHF) were more likely to receive beta-blockers and aspirin than were women. Meanwhile, women were more likely to be obese, have diabetes, or have atrial fibrillation.

"Perhaps there are differences in the pathophysiology of AHF between women and men, which should be taken into account in order to achieve gender-tailored management," said Dr. John Parissis, who presented the study at the annual congress of the European Society of Cardiology.

The study was a subanalysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF), a chart audit survey of 4,953 patients hospitalized for AHF in 666 hospitals in nine countries (France, Germany, Spain, Italy, Greece, United Kingdom, Turkey, Australia, and Mexico.)

Women made up 37% of the patients, consistent with ratios in other registries, said Dr. Parissis of Attikon University Hospital, Greece. They presented with AHF at an older age and had higher rates of de novo heart failure. They were also half as likely as were men to present with cardiogenic shock, but more than twice as likely to have right heart failure.

The study showed that women hospitalized with AHF had a higher prevalence of diabetes (47% v. 43%), obesity (30% v. 25%), anemia (17% v. 13%), atrial fibrillation or flutter (49% v. 42%), dementia (6% v. 3%), and depression (11% v. 7%), compared with men.

Meanwhile, men had a higher prevalence of chronic obstructive pulmonary disease (COPD) and asthma (27% v. 21%), and coronary artery disease (CAD) (35% v. 24%) compared with women.

Upon admission, women were less likely than were men to receive aspirin, clopidogrel, and beta-blockers, because of their comorbidities and lower rates of CAD. But compared with men, they were more likely to be on angiotensin receptors blockers and digitalis treatment, because of higher incidence of atrial fibrillation, according to the investigators.

There were no significant differences in use of ACE inhibitors, diuretics, and nitrates between genders, the analysis showed.

Both genders received continuous positive airway pressure (CPAP) and mechanical ventilation. Fewer women, however, were supported by intra-aortic balloon pump (IABP), underwent percutaneous coronary intervention, or had coronary artery bypass graft surgery.

In addition, in-hospital mortality was similar between genders (10.5% for men vs 11.1% for women). "The presence of higher ejection fraction and less CAD in women may positively affect survival in women," said Dr. Parissis.

But, "the existence of other serious comorbidities and underprescription of life saving medications such as beta-blockers may counteract this positive effect on their in-hospital survival," he added. "This point may explain the similar mortality rate between genders."

At discharge, the proportion of patients treated with medications increased. Nevertheless, the differences between genders remained significant, the authors wrote.

The differences in treatment call for "a more intensive implementation of heart failure guidelines to optimize life saving medications, especially in women," said Dr. Parissis.

Dr. Parissis is a member of the ALARM-HF Steering Committee and presented the study on the committee’s behalf. He said he had received research grants from Abbott and Orion Pharma.

MUNICH – Gender differences in comorbidities affected the medications prescribed to men and women hospitalized with acute heart failure, although their in-hospital mortality rate remained similar, according to a retrospective analysis of nearly 5,000 hospital charts.

The study showed that men who were hospitalized with acute heart failure (AHF) were more likely to receive beta-blockers and aspirin than were women. Meanwhile, women were more likely to be obese, have diabetes, or have atrial fibrillation.

"Perhaps there are differences in the pathophysiology of AHF between women and men, which should be taken into account in order to achieve gender-tailored management," said Dr. John Parissis, who presented the study at the annual congress of the European Society of Cardiology.

The study was a subanalysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF), a chart audit survey of 4,953 patients hospitalized for AHF in 666 hospitals in nine countries (France, Germany, Spain, Italy, Greece, United Kingdom, Turkey, Australia, and Mexico.)

Women made up 37% of the patients, consistent with ratios in other registries, said Dr. Parissis of Attikon University Hospital, Greece. They presented with AHF at an older age and had higher rates of de novo heart failure. They were also half as likely as were men to present with cardiogenic shock, but more than twice as likely to have right heart failure.

The study showed that women hospitalized with AHF had a higher prevalence of diabetes (47% v. 43%), obesity (30% v. 25%), anemia (17% v. 13%), atrial fibrillation or flutter (49% v. 42%), dementia (6% v. 3%), and depression (11% v. 7%), compared with men.

Meanwhile, men had a higher prevalence of chronic obstructive pulmonary disease (COPD) and asthma (27% v. 21%), and coronary artery disease (CAD) (35% v. 24%) compared with women.

Upon admission, women were less likely than were men to receive aspirin, clopidogrel, and beta-blockers, because of their comorbidities and lower rates of CAD. But compared with men, they were more likely to be on angiotensin receptors blockers and digitalis treatment, because of higher incidence of atrial fibrillation, according to the investigators.

There were no significant differences in use of ACE inhibitors, diuretics, and nitrates between genders, the analysis showed.

Both genders received continuous positive airway pressure (CPAP) and mechanical ventilation. Fewer women, however, were supported by intra-aortic balloon pump (IABP), underwent percutaneous coronary intervention, or had coronary artery bypass graft surgery.

In addition, in-hospital mortality was similar between genders (10.5% for men vs 11.1% for women). "The presence of higher ejection fraction and less CAD in women may positively affect survival in women," said Dr. Parissis.

But, "the existence of other serious comorbidities and underprescription of life saving medications such as beta-blockers may counteract this positive effect on their in-hospital survival," he added. "This point may explain the similar mortality rate between genders."

At discharge, the proportion of patients treated with medications increased. Nevertheless, the differences between genders remained significant, the authors wrote.

The differences in treatment call for "a more intensive implementation of heart failure guidelines to optimize life saving medications, especially in women," said Dr. Parissis.

Dr. Parissis is a member of the ALARM-HF Steering Committee and presented the study on the committee’s behalf. He said he had received research grants from Abbott and Orion Pharma.

Most women with heart disease can safely go through pregnancy, although striking differences in outcome were found by type of heart disease and between countries, a novel international registry shows.

Maternal mortality was 1%, but this was still 100 times higher than the mortality of 0.007% in the normal pregnant population. Seven of the 13 maternal deaths were due to cardiac events, three to thromboembolic events, and three to sepsis.

Maternal mortality was highest in women with cardiomyopathy at 2.4%, compared with 2.1% for those with valvular heart disease, 0.5% with congenital heart disease, and 0% for ischemic heart disease.

In addition, women with cardiomyopathy experienced higher rates of heart failure (24% vs. 18%, 8%, and 8%) and ventricular arrhythmias (11% vs. 0.6%, 1.6%, and 0%) than did those with valvular heart disease, congenital heart disease, and ischemic heart disease, cardiologist Dr. Jolien Roos-Hesselink and her associates reported (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs270]).

Although cardiomyopathy is uncommon during pregnancy, it is difficult to manage in the context of left ventricular dysfunction or peripartum cardiomyopathy, with a high risk of an adverse outcome for both the mother and the baby, observed Dr. Roos-Hesselink of Erasmus Medical Center, Rotterdam, the Netherlands, and associates.

The analysis was based on 1,321 pregnant patients with structural or ischemic heart disease enrolled from 60 hospitals in 28 countries from 2008 to June 2011 in the European Registry on Pregnancy and Heart Disease, the world’s first registry to focus on this challenging clinical scenario.

The patients’ median age was 30 (range 16-53), median duration of pregnancy 38 weeks, 56% had one or more previous pregnancy, and 54% had undergone at least one prior cardiac intervention. About 50 patients were from the United States.

Most patients were New York Heart Association class I (70%), and only 0.3% were class IV. More women with cardiomyopathy were NYHA class III (8%), while those with ischemic heart disease were older, more likely to suffer from hypertension and diabetes, and more likely to be smokers.

Outcomes in women with congenital heart disease, the largest subgroup in the registry at 872 patients, were relatively good compared with other subgroups. The authors attributed this to the high rate of successful prior cardiac corrective surgery (66%), favorable NYHA class (76% class I and 21% class II) and low use of any medication (20%).

Even in this group, however, the rate of cesarean delivery was higher (38% vs. 23%) and mean birth weight was lower than in the background population (3,056 grams vs. 3,190 grams), Dr. Roos-Hesselink and associates noted.

Overall, 41% of the cohort had a cesarean delivery, with the highest rate in women with ischemic heart disease (60%) or cardiomyopathy (58%).

Cesarean delivery rates also varied widely between countries, with the highest rate reported in Italy, not the United States, she said in an interview.

"C-section rates are the product both of the background rates of a particular country and the numbers of women with severe heart disease, so that if the background rate was high and there were more women with severe heart disease in that group, then that country’s rates were higher," she explained.

During pregnancy, 338 patients (26%) were hospitalized, most (76%) only once. In all, 162 patients (12%) "had at least one period of heart failure during or after pregnancy, while this is rarely, if ever, seen in the general population," the investigators said.

Fetal mortality was significantly higher in the cohort than in the normal population (1.7% vs. 0.35%). In the cohort, 62% of the deaths were intrauterine fetal deaths with no further information, 21% were obviously due to the maternal condition, and 17% were because of structural fetal abnormalities. Neonatal death rates did not differ significantly between the cohort and the normal population (0.6% vs. 0.4%).

As for whether certain women with heart disease should avoid pregnancy, the data show there are certain groups of women who have a very high chance of experiencing an adverse outcome during pregnancy, but ultimately it is an individual’s choice whether to undergo a pregnancy, coauthor Dr. Mark R. Johnson, clinical chair in obstetrics at Imperial College, London, said in an interview.

The doctor’s job is to give advice about the risks," he said. One of the reasons the registry is so important is that "it gives us a more robust source to base our advice on."

Dr. Roos-Hesselink pointed out that guidelines published in Europe last year do consider some groups to be contraindicated for pregnancy including patients with pulmonary hypertension, patients with severe cyanosis, and patients with earlier peripartum cardiomyopathy and still diminished ventricular function.

"Some of these women do get pregnant against advice," she added. "Especially, we have seen this happen in Egypt," she said, noting that women who wanted a pregnancy for cultural reasons might not tell their husbands that they had heart defects.

Significant differences were found between developed and developing countries in maternal mortality (0.6% vs. 3.9%) and fetal death (0.9% vs. 6.5%), although the authors acknowledged that any between-country comparisons were "very fragile" because the size of the populations was "grossly unbalanced."

"Most women with adequate counseling and optimal care should not be discouraged and can go safely through pregnancy," the authors concluded.

In terms of counseling, Dr. Johnson said it’s important to give as accurate a picture as possible of the risks to which the woman would be exposing herself and her baby.

"In terms of management, the early recognition of a problem and its prompt management is really important, from things as simple as anemia or a urinary tract infection to the more severe situation of a cardiac arrhythmia or the development of heart failure," he said.

Dr. Roos-Hesselink said the standard at her clinic is to perform an echocardiogram and exercise test prepregnancy, with other tests such as magnetic resonance imaging done if needed. Symptomatic patients must be treated and a dilated aorta corrected prior to pregnancy.

"If the woman has a bad exercise capacity, this gives you an idea she will do badly during pregnancy," she added.

The study was supported by the European Society of Cardiology. The authors reported they have no conflicts of interest.

Most women with heart disease can safely go through pregnancy, although striking differences in outcome were found by type of heart disease and between countries, a novel international registry shows.

Maternal mortality was 1%, but this was still 100 times higher than the mortality of 0.007% in the normal pregnant population. Seven of the 13 maternal deaths were due to cardiac events, three to thromboembolic events, and three to sepsis.

Maternal mortality was highest in women with cardiomyopathy at 2.4%, compared with 2.1% for those with valvular heart disease, 0.5% with congenital heart disease, and 0% for ischemic heart disease.

In addition, women with cardiomyopathy experienced higher rates of heart failure (24% vs. 18%, 8%, and 8%) and ventricular arrhythmias (11% vs. 0.6%, 1.6%, and 0%) than did those with valvular heart disease, congenital heart disease, and ischemic heart disease, cardiologist Dr. Jolien Roos-Hesselink and her associates reported (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs270]).

Although cardiomyopathy is uncommon during pregnancy, it is difficult to manage in the context of left ventricular dysfunction or peripartum cardiomyopathy, with a high risk of an adverse outcome for both the mother and the baby, observed Dr. Roos-Hesselink of Erasmus Medical Center, Rotterdam, the Netherlands, and associates.

The analysis was based on 1,321 pregnant patients with structural or ischemic heart disease enrolled from 60 hospitals in 28 countries from 2008 to June 2011 in the European Registry on Pregnancy and Heart Disease, the world’s first registry to focus on this challenging clinical scenario.

The patients’ median age was 30 (range 16-53), median duration of pregnancy 38 weeks, 56% had one or more previous pregnancy, and 54% had undergone at least one prior cardiac intervention. About 50 patients were from the United States.

Most patients were New York Heart Association class I (70%), and only 0.3% were class IV. More women with cardiomyopathy were NYHA class III (8%), while those with ischemic heart disease were older, more likely to suffer from hypertension and diabetes, and more likely to be smokers.

Outcomes in women with congenital heart disease, the largest subgroup in the registry at 872 patients, were relatively good compared with other subgroups. The authors attributed this to the high rate of successful prior cardiac corrective surgery (66%), favorable NYHA class (76% class I and 21% class II) and low use of any medication (20%).

Even in this group, however, the rate of cesarean delivery was higher (38% vs. 23%) and mean birth weight was lower than in the background population (3,056 grams vs. 3,190 grams), Dr. Roos-Hesselink and associates noted.

Overall, 41% of the cohort had a cesarean delivery, with the highest rate in women with ischemic heart disease (60%) or cardiomyopathy (58%).

Cesarean delivery rates also varied widely between countries, with the highest rate reported in Italy, not the United States, she said in an interview.

"C-section rates are the product both of the background rates of a particular country and the numbers of women with severe heart disease, so that if the background rate was high and there were more women with severe heart disease in that group, then that country’s rates were higher," she explained.

During pregnancy, 338 patients (26%) were hospitalized, most (76%) only once. In all, 162 patients (12%) "had at least one period of heart failure during or after pregnancy, while this is rarely, if ever, seen in the general population," the investigators said.

Fetal mortality was significantly higher in the cohort than in the normal population (1.7% vs. 0.35%). In the cohort, 62% of the deaths were intrauterine fetal deaths with no further information, 21% were obviously due to the maternal condition, and 17% were because of structural fetal abnormalities. Neonatal death rates did not differ significantly between the cohort and the normal population (0.6% vs. 0.4%).

As for whether certain women with heart disease should avoid pregnancy, the data show there are certain groups of women who have a very high chance of experiencing an adverse outcome during pregnancy, but ultimately it is an individual’s choice whether to undergo a pregnancy, coauthor Dr. Mark R. Johnson, clinical chair in obstetrics at Imperial College, London, said in an interview.

The doctor’s job is to give advice about the risks," he said. One of the reasons the registry is so important is that "it gives us a more robust source to base our advice on."

Dr. Roos-Hesselink pointed out that guidelines published in Europe last year do consider some groups to be contraindicated for pregnancy including patients with pulmonary hypertension, patients with severe cyanosis, and patients with earlier peripartum cardiomyopathy and still diminished ventricular function.

"Some of these women do get pregnant against advice," she added. "Especially, we have seen this happen in Egypt," she said, noting that women who wanted a pregnancy for cultural reasons might not tell their husbands that they had heart defects.

Significant differences were found between developed and developing countries in maternal mortality (0.6% vs. 3.9%) and fetal death (0.9% vs. 6.5%), although the authors acknowledged that any between-country comparisons were "very fragile" because the size of the populations was "grossly unbalanced."

"Most women with adequate counseling and optimal care should not be discouraged and can go safely through pregnancy," the authors concluded.

In terms of counseling, Dr. Johnson said it’s important to give as accurate a picture as possible of the risks to which the woman would be exposing herself and her baby.

"In terms of management, the early recognition of a problem and its prompt management is really important, from things as simple as anemia or a urinary tract infection to the more severe situation of a cardiac arrhythmia or the development of heart failure," he said.

Dr. Roos-Hesselink said the standard at her clinic is to perform an echocardiogram and exercise test prepregnancy, with other tests such as magnetic resonance imaging done if needed. Symptomatic patients must be treated and a dilated aorta corrected prior to pregnancy.

"If the woman has a bad exercise capacity, this gives you an idea she will do badly during pregnancy," she added.

The study was supported by the European Society of Cardiology. The authors reported they have no conflicts of interest.

Most women with heart disease can safely go through pregnancy, although striking differences in outcome were found by type of heart disease and between countries, a novel international registry shows.

Maternal mortality was 1%, but this was still 100 times higher than the mortality of 0.007% in the normal pregnant population. Seven of the 13 maternal deaths were due to cardiac events, three to thromboembolic events, and three to sepsis.

Maternal mortality was highest in women with cardiomyopathy at 2.4%, compared with 2.1% for those with valvular heart disease, 0.5% with congenital heart disease, and 0% for ischemic heart disease.

In addition, women with cardiomyopathy experienced higher rates of heart failure (24% vs. 18%, 8%, and 8%) and ventricular arrhythmias (11% vs. 0.6%, 1.6%, and 0%) than did those with valvular heart disease, congenital heart disease, and ischemic heart disease, cardiologist Dr. Jolien Roos-Hesselink and her associates reported (Eur. Heart J. 2012 [doi:10.1093/eurheartj/ehs270]).

Although cardiomyopathy is uncommon during pregnancy, it is difficult to manage in the context of left ventricular dysfunction or peripartum cardiomyopathy, with a high risk of an adverse outcome for both the mother and the baby, observed Dr. Roos-Hesselink of Erasmus Medical Center, Rotterdam, the Netherlands, and associates.

The analysis was based on 1,321 pregnant patients with structural or ischemic heart disease enrolled from 60 hospitals in 28 countries from 2008 to June 2011 in the European Registry on Pregnancy and Heart Disease, the world’s first registry to focus on this challenging clinical scenario.

The patients’ median age was 30 (range 16-53), median duration of pregnancy 38 weeks, 56% had one or more previous pregnancy, and 54% had undergone at least one prior cardiac intervention. About 50 patients were from the United States.

Most patients were New York Heart Association class I (70%), and only 0.3% were class IV. More women with cardiomyopathy were NYHA class III (8%), while those with ischemic heart disease were older, more likely to suffer from hypertension and diabetes, and more likely to be smokers.

Outcomes in women with congenital heart disease, the largest subgroup in the registry at 872 patients, were relatively good compared with other subgroups. The authors attributed this to the high rate of successful prior cardiac corrective surgery (66%), favorable NYHA class (76% class I and 21% class II) and low use of any medication (20%).

Even in this group, however, the rate of cesarean delivery was higher (38% vs. 23%) and mean birth weight was lower than in the background population (3,056 grams vs. 3,190 grams), Dr. Roos-Hesselink and associates noted.

Overall, 41% of the cohort had a cesarean delivery, with the highest rate in women with ischemic heart disease (60%) or cardiomyopathy (58%).

Cesarean delivery rates also varied widely between countries, with the highest rate reported in Italy, not the United States, she said in an interview.

"C-section rates are the product both of the background rates of a particular country and the numbers of women with severe heart disease, so that if the background rate was high and there were more women with severe heart disease in that group, then that country’s rates were higher," she explained.

During pregnancy, 338 patients (26%) were hospitalized, most (76%) only once. In all, 162 patients (12%) "had at least one period of heart failure during or after pregnancy, while this is rarely, if ever, seen in the general population," the investigators said.

Fetal mortality was significantly higher in the cohort than in the normal population (1.7% vs. 0.35%). In the cohort, 62% of the deaths were intrauterine fetal deaths with no further information, 21% were obviously due to the maternal condition, and 17% were because of structural fetal abnormalities. Neonatal death rates did not differ significantly between the cohort and the normal population (0.6% vs. 0.4%).

As for whether certain women with heart disease should avoid pregnancy, the data show there are certain groups of women who have a very high chance of experiencing an adverse outcome during pregnancy, but ultimately it is an individual’s choice whether to undergo a pregnancy, coauthor Dr. Mark R. Johnson, clinical chair in obstetrics at Imperial College, London, said in an interview.

The doctor’s job is to give advice about the risks," he said. One of the reasons the registry is so important is that "it gives us a more robust source to base our advice on."

Dr. Roos-Hesselink pointed out that guidelines published in Europe last year do consider some groups to be contraindicated for pregnancy including patients with pulmonary hypertension, patients with severe cyanosis, and patients with earlier peripartum cardiomyopathy and still diminished ventricular function.

"Some of these women do get pregnant against advice," she added. "Especially, we have seen this happen in Egypt," she said, noting that women who wanted a pregnancy for cultural reasons might not tell their husbands that they had heart defects.

Significant differences were found between developed and developing countries in maternal mortality (0.6% vs. 3.9%) and fetal death (0.9% vs. 6.5%), although the authors acknowledged that any between-country comparisons were "very fragile" because the size of the populations was "grossly unbalanced."

"Most women with adequate counseling and optimal care should not be discouraged and can go safely through pregnancy," the authors concluded.

In terms of counseling, Dr. Johnson said it’s important to give as accurate a picture as possible of the risks to which the woman would be exposing herself and her baby.

"In terms of management, the early recognition of a problem and its prompt management is really important, from things as simple as anemia or a urinary tract infection to the more severe situation of a cardiac arrhythmia or the development of heart failure," he said.

Dr. Roos-Hesselink said the standard at her clinic is to perform an echocardiogram and exercise test prepregnancy, with other tests such as magnetic resonance imaging done if needed. Symptomatic patients must be treated and a dilated aorta corrected prior to pregnancy.

"If the woman has a bad exercise capacity, this gives you an idea she will do badly during pregnancy," she added.

The study was supported by the European Society of Cardiology. The authors reported they have no conflicts of interest.

SEATTLE – Isolated left ventricular diastolic dysfunction should not be viewed as a reason to withhold ablation therapy in patients with atrial fibrillation and preserved ejection fraction, new data suggest.

Investigators led by Dr. Rosita Zakeri studied a series of 707 patients who were undergoing a first catheter ablation at the Mayo Clinic for symptomatic, drug-refractory atrial fibrillation and who had preserved left ventricular ejection fraction.

Fully 34% had isolated diastolic dysfunction (a left atrial pressure of greater than 15 mm as measured directly by the transseptal approach), according to results reported at the annual meeting of the Heart Failure Society of America.

Patients with isolated diastolic dysfunction had a marginally elevated risk of recurrence of atrial fibrillation at 1 year in a univariate analysis but not after multivariate adjustment. In addition, they derived a similar improvement in quality of life from ablation.

"Although diastolic dysfunction was associated with an increased risk of atrial fibrillation recurrence, in and of itself, it does not appear to be a key arrhythmogenic factor nor strongly related to quality of life at 1 year after ablation," commented Dr. Zakeri, who is a cardiology fellow at the Mayo Clinic in Rochester, Minn.

"Therefore ... the presence of left ventricular diastolic dysfunction should not necessarily discourage the use of catheter ablation for treatment of symptomatic atrial fibrillation in this patient group," she said.

Diastolic dysfunction increases susceptibility to atrial fibrillation, but it is unclear whether it has a continued proarrhythmic effect after ablation, Dr. Zakeri noted.

"We also know that diastolic dysfunction predisposes to heart failure and is one of the hemodynamic hallmarks of heart failure with preserved ejection fraction," she continued. And some patients with atrial fibrillation having diastolic dysfunction may have early heart failure, with the arrhythmia accelerating the severity or presentation of symptoms.

Study results showed that relative to other patients, the patients with isolated diastolic dysfunction had a higher body mass index; had greater prevalences of diabetes, hypertension, and heart failure; were more likely to have nonparoxysmal atrial fibrillation; and had poorer quality of life as assessed with both the Medical Outcomes Study 36-item questionnaire (SF-36) and the Mayo AF-specific Symptom Inventory (MAFSI).

Overall, 21.1% of patients had a recurrence of atrial fibrillation at 1 year, Dr. Zakeri reported. The rate was 25.3% in patients with diastolic dysfunction and 18.9% in patients without it.

The difference corresponded to a marginally elevated risk of recurrence for the group with diastolic dysfunction in unadjusted analyses (odds ratio, 1.45; P = .05), but after adjustment for age, sex, type of atrial fibrillation, and left atrial volume index, there was no significant association.

When patients were stratified by baseline left atrial pressure – less than 12 mm Hg, 12-15 mm Hg, or greater than 15 mm Hg – all three groups had significant improvements at 1 year in scores on the quality of life scales, with no significant difference in the magnitude of improvement between them.

Dr. Zakeri disclosed no relevant conflicts of interest.

SEATTLE – Isolated left ventricular diastolic dysfunction should not be viewed as a reason to withhold ablation therapy in patients with atrial fibrillation and preserved ejection fraction, new data suggest.

Investigators led by Dr. Rosita Zakeri studied a series of 707 patients who were undergoing a first catheter ablation at the Mayo Clinic for symptomatic, drug-refractory atrial fibrillation and who had preserved left ventricular ejection fraction.

Fully 34% had isolated diastolic dysfunction (a left atrial pressure of greater than 15 mm as measured directly by the transseptal approach), according to results reported at the annual meeting of the Heart Failure Society of America.

Patients with isolated diastolic dysfunction had a marginally elevated risk of recurrence of atrial fibrillation at 1 year in a univariate analysis but not after multivariate adjustment. In addition, they derived a similar improvement in quality of life from ablation.

"Although diastolic dysfunction was associated with an increased risk of atrial fibrillation recurrence, in and of itself, it does not appear to be a key arrhythmogenic factor nor strongly related to quality of life at 1 year after ablation," commented Dr. Zakeri, who is a cardiology fellow at the Mayo Clinic in Rochester, Minn.

"Therefore ... the presence of left ventricular diastolic dysfunction should not necessarily discourage the use of catheter ablation for treatment of symptomatic atrial fibrillation in this patient group," she said.

Diastolic dysfunction increases susceptibility to atrial fibrillation, but it is unclear whether it has a continued proarrhythmic effect after ablation, Dr. Zakeri noted.

"We also know that diastolic dysfunction predisposes to heart failure and is one of the hemodynamic hallmarks of heart failure with preserved ejection fraction," she continued. And some patients with atrial fibrillation having diastolic dysfunction may have early heart failure, with the arrhythmia accelerating the severity or presentation of symptoms.

Study results showed that relative to other patients, the patients with isolated diastolic dysfunction had a higher body mass index; had greater prevalences of diabetes, hypertension, and heart failure; were more likely to have nonparoxysmal atrial fibrillation; and had poorer quality of life as assessed with both the Medical Outcomes Study 36-item questionnaire (SF-36) and the Mayo AF-specific Symptom Inventory (MAFSI).

Overall, 21.1% of patients had a recurrence of atrial fibrillation at 1 year, Dr. Zakeri reported. The rate was 25.3% in patients with diastolic dysfunction and 18.9% in patients without it.

The difference corresponded to a marginally elevated risk of recurrence for the group with diastolic dysfunction in unadjusted analyses (odds ratio, 1.45; P = .05), but after adjustment for age, sex, type of atrial fibrillation, and left atrial volume index, there was no significant association.

When patients were stratified by baseline left atrial pressure – less than 12 mm Hg, 12-15 mm Hg, or greater than 15 mm Hg – all three groups had significant improvements at 1 year in scores on the quality of life scales, with no significant difference in the magnitude of improvement between them.

Dr. Zakeri disclosed no relevant conflicts of interest.

SEATTLE – Isolated left ventricular diastolic dysfunction should not be viewed as a reason to withhold ablation therapy in patients with atrial fibrillation and preserved ejection fraction, new data suggest.

Investigators led by Dr. Rosita Zakeri studied a series of 707 patients who were undergoing a first catheter ablation at the Mayo Clinic for symptomatic, drug-refractory atrial fibrillation and who had preserved left ventricular ejection fraction.

Fully 34% had isolated diastolic dysfunction (a left atrial pressure of greater than 15 mm as measured directly by the transseptal approach), according to results reported at the annual meeting of the Heart Failure Society of America.

Patients with isolated diastolic dysfunction had a marginally elevated risk of recurrence of atrial fibrillation at 1 year in a univariate analysis but not after multivariate adjustment. In addition, they derived a similar improvement in quality of life from ablation.

"Although diastolic dysfunction was associated with an increased risk of atrial fibrillation recurrence, in and of itself, it does not appear to be a key arrhythmogenic factor nor strongly related to quality of life at 1 year after ablation," commented Dr. Zakeri, who is a cardiology fellow at the Mayo Clinic in Rochester, Minn.

"Therefore ... the presence of left ventricular diastolic dysfunction should not necessarily discourage the use of catheter ablation for treatment of symptomatic atrial fibrillation in this patient group," she said.

Diastolic dysfunction increases susceptibility to atrial fibrillation, but it is unclear whether it has a continued proarrhythmic effect after ablation, Dr. Zakeri noted.

"We also know that diastolic dysfunction predisposes to heart failure and is one of the hemodynamic hallmarks of heart failure with preserved ejection fraction," she continued. And some patients with atrial fibrillation having diastolic dysfunction may have early heart failure, with the arrhythmia accelerating the severity or presentation of symptoms.

Study results showed that relative to other patients, the patients with isolated diastolic dysfunction had a higher body mass index; had greater prevalences of diabetes, hypertension, and heart failure; were more likely to have nonparoxysmal atrial fibrillation; and had poorer quality of life as assessed with both the Medical Outcomes Study 36-item questionnaire (SF-36) and the Mayo AF-specific Symptom Inventory (MAFSI).

Overall, 21.1% of patients had a recurrence of atrial fibrillation at 1 year, Dr. Zakeri reported. The rate was 25.3% in patients with diastolic dysfunction and 18.9% in patients without it.

The difference corresponded to a marginally elevated risk of recurrence for the group with diastolic dysfunction in unadjusted analyses (odds ratio, 1.45; P = .05), but after adjustment for age, sex, type of atrial fibrillation, and left atrial volume index, there was no significant association.

When patients were stratified by baseline left atrial pressure – less than 12 mm Hg, 12-15 mm Hg, or greater than 15 mm Hg – all three groups had significant improvements at 1 year in scores on the quality of life scales, with no significant difference in the magnitude of improvement between them.

Dr. Zakeri disclosed no relevant conflicts of interest.

BERLIN – Older patients with type 2 diabetes are very likely to have left ventricular dysfunction, even in the absence of any sign of cardiac disease.

However, at least some of this dysfunction can remit over time, perhaps as a result of effective diabetes treatment, Dr. Carlo Bruno Giorda said at the annual meeting of the European Association for the Study of Diabetes.

Dr. Giorda reported results of Left Ventricular Dysfunction in Diabetes (DYDA), a 2-year prospective study that tracked the development of left ventricular dysfunction in 957 patients with type 2 diabetes who did not have any signs of cardiac disease at baseline.

DYDA’s secondary end point was a combination of all-cause mortality and cardiovascular hospitalization; the study also sought to identify factors predicting these outcomes, said Dr. Giorda of the Ospedale Maggiore, Chieri, Italy.

The study defined left ventricular systolic dysfunction as an ejection fraction of less than 50% and/or a midwall fractional shortening of 15% or less. At baseline, all patients underwent an echocardiogram to determine left ventricular dysfunction. Imaging revealed that 60% of the cohort had some form of LVD – systolic (21%), diastolic (27%), or both (12%).

The patients were a mean of 61 years; 62% were men. Almost half (44%) were overweight and 35% were obese. The median heart rate was 72 beats per minute. The median blood pressure was 137/80.

Diabetes medications included sulfonylureas (43%), insulin (32%), repaglinide (11%), metformin (66%), acarbose (2%), and glitazones (5%). Most patients (60%) were hypertensive and being treated for that; 55% were taking medication for dyslipidemia.

Comorbidities included vascular disease (8%), diabetic retinopathy (13%), diabetic neuropathy (8%), and thyroid disease (8%). Others were chronic obstructive pulmonary disease (3%) and chronic kidney disease (2%).

Diabetes was well-controlled in the group, Dr. Giorda said. The median hemoglobin A_1c was 6.7%, and the median blood glucose 142 mg/dL. The median creatinine level was 0.90 mg/dL, and the median glomerular filtration rate, 84 mL/min.

By the 2-year mark, 15 patients had died; only 3 of these deaths were attributed to cardiovascular causes. Eleven patients had died of non-cardiovascular issues, and one death occurred of unknown etiology. There had been 181 hospitalizations among 139 patients. The majority of these (133) were for non–cardiovascular problems.

Dr. Giorda said the association with repaglinide was probably a chance finding. "We even controlled for renal insufficiency, since repaglinide is often used for those patients in Italy, and this relationship still emerged."

At the end of the study period, new onset systolic dysfunction had developed in 17% and diastolic in 22% of the initially negative group.

A multivariate analysis identified several baseline factors that significantly predicted the development of LVD, including age (67 years vs. 56 years), HbA_1c (7.6% vs. 6%), and heart rate (90 vs. 68 beats per minute.

A surprise finding, however, was that LVD remitted in several patients, Dr. Giorda said. "There was reversal of LVD in 12% of the patients who had it at baseline. We can’t say why it reversed ... maybe it was due to [diabetes treatment]. But we can say that in some patients, LVD can be considered temporary."

Dr. Giorda had no financial disclosures.

BERLIN – Older patients with type 2 diabetes are very likely to have left ventricular dysfunction, even in the absence of any sign of cardiac disease.

However, at least some of this dysfunction can remit over time, perhaps as a result of effective diabetes treatment, Dr. Carlo Bruno Giorda said at the annual meeting of the European Association for the Study of Diabetes.

Dr. Giorda reported results of Left Ventricular Dysfunction in Diabetes (DYDA), a 2-year prospective study that tracked the development of left ventricular dysfunction in 957 patients with type 2 diabetes who did not have any signs of cardiac disease at baseline.

DYDA’s secondary end point was a combination of all-cause mortality and cardiovascular hospitalization; the study also sought to identify factors predicting these outcomes, said Dr. Giorda of the Ospedale Maggiore, Chieri, Italy.

The study defined left ventricular systolic dysfunction as an ejection fraction of less than 50% and/or a midwall fractional shortening of 15% or less. At baseline, all patients underwent an echocardiogram to determine left ventricular dysfunction. Imaging revealed that 60% of the cohort had some form of LVD – systolic (21%), diastolic (27%), or both (12%).

The patients were a mean of 61 years; 62% were men. Almost half (44%) were overweight and 35% were obese. The median heart rate was 72 beats per minute. The median blood pressure was 137/80.

Diabetes medications included sulfonylureas (43%), insulin (32%), repaglinide (11%), metformin (66%), acarbose (2%), and glitazones (5%). Most patients (60%) were hypertensive and being treated for that; 55% were taking medication for dyslipidemia.

Comorbidities included vascular disease (8%), diabetic retinopathy (13%), diabetic neuropathy (8%), and thyroid disease (8%). Others were chronic obstructive pulmonary disease (3%) and chronic kidney disease (2%).

Diabetes was well-controlled in the group, Dr. Giorda said. The median hemoglobin A_1c was 6.7%, and the median blood glucose 142 mg/dL. The median creatinine level was 0.90 mg/dL, and the median glomerular filtration rate, 84 mL/min.

By the 2-year mark, 15 patients had died; only 3 of these deaths were attributed to cardiovascular causes. Eleven patients had died of non-cardiovascular issues, and one death occurred of unknown etiology. There had been 181 hospitalizations among 139 patients. The majority of these (133) were for non–cardiovascular problems.

Dr. Giorda said the association with repaglinide was probably a chance finding. "We even controlled for renal insufficiency, since repaglinide is often used for those patients in Italy, and this relationship still emerged."

At the end of the study period, new onset systolic dysfunction had developed in 17% and diastolic in 22% of the initially negative group.

A multivariate analysis identified several baseline factors that significantly predicted the development of LVD, including age (67 years vs. 56 years), HbA_1c (7.6% vs. 6%), and heart rate (90 vs. 68 beats per minute.

A surprise finding, however, was that LVD remitted in several patients, Dr. Giorda said. "There was reversal of LVD in 12% of the patients who had it at baseline. We can’t say why it reversed ... maybe it was due to [diabetes treatment]. But we can say that in some patients, LVD can be considered temporary."

Dr. Giorda had no financial disclosures.

BERLIN – Older patients with type 2 diabetes are very likely to have left ventricular dysfunction, even in the absence of any sign of cardiac disease.

However, at least some of this dysfunction can remit over time, perhaps as a result of effective diabetes treatment, Dr. Carlo Bruno Giorda said at the annual meeting of the European Association for the Study of Diabetes.

Dr. Giorda reported results of Left Ventricular Dysfunction in Diabetes (DYDA), a 2-year prospective study that tracked the development of left ventricular dysfunction in 957 patients with type 2 diabetes who did not have any signs of cardiac disease at baseline.

DYDA’s secondary end point was a combination of all-cause mortality and cardiovascular hospitalization; the study also sought to identify factors predicting these outcomes, said Dr. Giorda of the Ospedale Maggiore, Chieri, Italy.

The study defined left ventricular systolic dysfunction as an ejection fraction of less than 50% and/or a midwall fractional shortening of 15% or less. At baseline, all patients underwent an echocardiogram to determine left ventricular dysfunction. Imaging revealed that 60% of the cohort had some form of LVD – systolic (21%), diastolic (27%), or both (12%).

The patients were a mean of 61 years; 62% were men. Almost half (44%) were overweight and 35% were obese. The median heart rate was 72 beats per minute. The median blood pressure was 137/80.

Diabetes medications included sulfonylureas (43%), insulin (32%), repaglinide (11%), metformin (66%), acarbose (2%), and glitazones (5%). Most patients (60%) were hypertensive and being treated for that; 55% were taking medication for dyslipidemia.

Comorbidities included vascular disease (8%), diabetic retinopathy (13%), diabetic neuropathy (8%), and thyroid disease (8%). Others were chronic obstructive pulmonary disease (3%) and chronic kidney disease (2%).

Diabetes was well-controlled in the group, Dr. Giorda said. The median hemoglobin A_1c was 6.7%, and the median blood glucose 142 mg/dL. The median creatinine level was 0.90 mg/dL, and the median glomerular filtration rate, 84 mL/min.

By the 2-year mark, 15 patients had died; only 3 of these deaths were attributed to cardiovascular causes. Eleven patients had died of non-cardiovascular issues, and one death occurred of unknown etiology. There had been 181 hospitalizations among 139 patients. The majority of these (133) were for non–cardiovascular problems.

Dr. Giorda said the association with repaglinide was probably a chance finding. "We even controlled for renal insufficiency, since repaglinide is often used for those patients in Italy, and this relationship still emerged."

At the end of the study period, new onset systolic dysfunction had developed in 17% and diastolic in 22% of the initially negative group.

A multivariate analysis identified several baseline factors that significantly predicted the development of LVD, including age (67 years vs. 56 years), HbA_1c (7.6% vs. 6%), and heart rate (90 vs. 68 beats per minute.

A surprise finding, however, was that LVD remitted in several patients, Dr. Giorda said. "There was reversal of LVD in 12% of the patients who had it at baseline. We can’t say why it reversed ... maybe it was due to [diabetes treatment]. But we can say that in some patients, LVD can be considered temporary."

Dr. Giorda had no financial disclosures.

SEATTLE – Patients with heart failure still benefit from spironolactone therapy even when they develop elevated potassium levels, a well-known and potentially life-threatening side effect of the medication, new data suggest.

Investigators led by Orly Vardeny, Pharm.D., conducted a secondary analysis of data from the RALES (Randomized Aldactone Evaluation Study) trial, in which more than 1,500 patients with heart failure were assigned to spironolactone (Aldactone) or placebo.

The spironolactone group had nearly quadruple the risk of hyperkalemia compared with the placebo group, she reported at the annual meeting of the Heart Failure Society of America. And hyperkalemia was indeed associated with a higher mortality rate.

But relative to their placebo-treated counterparts who did not have elevated potassium levels, spironolactone-treated patients who had elevated potassium levels, up to a serum potassium level of at least 5.5 mEq/L, were still less likely to die.

"The benefits of spironolactone are maintained in patients with mild to moderate hyperkalemia, and even in patients with potassium levels approaching 6.0 mEq/L," commented Dr. Vardeny, who is an associate professor of pharmacy at the University of Wisconsin in Madison.

"Our data argue for strategies that maintain spironolactone or aldosterone antagonist therapy even in the setting of mild to moderate hyperkalemia," she maintained.

"How many of these patients were on digoxin, and did you factor that into the analysis?" asked session comoderator Dr. Carl V. Leier of the Ohio State University Medical Center in Columbus.

Dr. Vardeny replied that analyses did not adjust for digoxin use, but they did adjust for age, estimated glomerular filtration rate, baseline potassium level, and diabetes.

"It seems that hypokalemia was more dangerous than hyperkalemia," commented attendee Dr. Edward Gilbert of the University of Utah in Salt Lake City. Might some of the benefit of spironolactone actually be related to reduced hypokalemia, he wondered.

"My personal bias is that there could be an association. This is really difficult to prove, only because potassium will vary so much, so the data will inform multiple categories of potassium," Dr. Vardeny replied. "But yes, we are investigating that as well."

The 1,663 patients in RALES had moderate to severe heart failure with a left ventricular ejection fraction of less than 35%, and were already receiving an angiotensin-converting enzyme inhibitor with or without a diuretic. They were randomized evenly to 25 mg of spironolactone daily, with optional titration up to 50 mg daily or placebo.

Serum potassium levels were monitored regularly. If patients developed hyperkalemia, investigators could reduce the dose of study medication but were encouraged to first adjust doses of other medications.

Main RALES results, previously reported, showed that spironolactone treatment was associated with a 30% reduction in the risk of all-cause mortality and a 35% reduction in the risk of hospitalization for worsening of heart failure (N. Engl. J. Med. 1999;341:709-17).

The new analysis showed that both treatment groups had mean potassium levels of 4.3 mEq/L at baseline. But levels increased within the first month in the spironolactone group and remained persistently higher than those in the placebo group, by 0.25 mEq/L on average, throughout the trial.

Relative to their peers in the placebo group, patients in the spironolactone group were significantly less likely to develop hypokalemia (6.5% vs. 16.2%) and more likely to develop hyperkalemia (14.5% vs. 4.2%), Dr. Vardeny reported. Hypokalemia was defined as a potassium level of less than 3.5 mEq/L; hyperkalemia equalled a potassium level of greater than 5.5 mEq/L.

In the spironolactone group, the rate of death was fairly stable – at about 17 per 100 patient-years – for patients with potassium levels ranging from 3.5 to 6.0 mEq/L. But it was higher among patients with lower levels (about 42 per 100 patient-years) or higher levels (about 25 per 100 patient-years).

In a multivariate analysis, patients were more likely to develop hypokalemia if they were black (hazard ratio, 2.0) or had a higher New York Heart Association functional class (HR, 1.5), whereas they were less likely if they had a higher baseline potassium level (HR, 0.25) or received spironolactone (HR, 0.36).

Patients were more likely to develop hyperkalemia if they received spironolactone (HR, 3.7), had a higher baseline potassium level (HR, 2.4), or had a history of diabetes (HR, 1.9).

Compared with placebo-treated patients having potassium levels of less than 5.0 mEq/L, spironolactone-treated patients with elevated potassium levels still had a significantly lower risk of death with potassium levels up to 5.5 mEq/L, and they had a nonsignificantly lower risk with levels up to about 6.0 mEq/L.

Dr. Vardeny reported having no relevant conflicts of interest. The RALES trial was sponsored by Searle, manufacturer of Aldactone.

SEATTLE – Patients with heart failure still benefit from spironolactone therapy even when they develop elevated potassium levels, a well-known and potentially life-threatening side effect of the medication, new data suggest.

Investigators led by Orly Vardeny, Pharm.D., conducted a secondary analysis of data from the RALES (Randomized Aldactone Evaluation Study) trial, in which more than 1,500 patients with heart failure were assigned to spironolactone (Aldactone) or placebo.

The spironolactone group had nearly quadruple the risk of hyperkalemia compared with the placebo group, she reported at the annual meeting of the Heart Failure Society of America. And hyperkalemia was indeed associated with a higher mortality rate.

But relative to their placebo-treated counterparts who did not have elevated potassium levels, spironolactone-treated patients who had elevated potassium levels, up to a serum potassium level of at least 5.5 mEq/L, were still less likely to die.

"The benefits of spironolactone are maintained in patients with mild to moderate hyperkalemia, and even in patients with potassium levels approaching 6.0 mEq/L," commented Dr. Vardeny, who is an associate professor of pharmacy at the University of Wisconsin in Madison.

"Our data argue for strategies that maintain spironolactone or aldosterone antagonist therapy even in the setting of mild to moderate hyperkalemia," she maintained.

"How many of these patients were on digoxin, and did you factor that into the analysis?" asked session comoderator Dr. Carl V. Leier of the Ohio State University Medical Center in Columbus.

Dr. Vardeny replied that analyses did not adjust for digoxin use, but they did adjust for age, estimated glomerular filtration rate, baseline potassium level, and diabetes.

"It seems that hypokalemia was more dangerous than hyperkalemia," commented attendee Dr. Edward Gilbert of the University of Utah in Salt Lake City. Might some of the benefit of spironolactone actually be related to reduced hypokalemia, he wondered.

"My personal bias is that there could be an association. This is really difficult to prove, only because potassium will vary so much, so the data will inform multiple categories of potassium," Dr. Vardeny replied. "But yes, we are investigating that as well."

The 1,663 patients in RALES had moderate to severe heart failure with a left ventricular ejection fraction of less than 35%, and were already receiving an angiotensin-converting enzyme inhibitor with or without a diuretic. They were randomized evenly to 25 mg of spironolactone daily, with optional titration up to 50 mg daily or placebo.

Serum potassium levels were monitored regularly. If patients developed hyperkalemia, investigators could reduce the dose of study medication but were encouraged to first adjust doses of other medications.

Main RALES results, previously reported, showed that spironolactone treatment was associated with a 30% reduction in the risk of all-cause mortality and a 35% reduction in the risk of hospitalization for worsening of heart failure (N. Engl. J. Med. 1999;341:709-17).

The new analysis showed that both treatment groups had mean potassium levels of 4.3 mEq/L at baseline. But levels increased within the first month in the spironolactone group and remained persistently higher than those in the placebo group, by 0.25 mEq/L on average, throughout the trial.

Relative to their peers in the placebo group, patients in the spironolactone group were significantly less likely to develop hypokalemia (6.5% vs. 16.2%) and more likely to develop hyperkalemia (14.5% vs. 4.2%), Dr. Vardeny reported. Hypokalemia was defined as a potassium level of less than 3.5 mEq/L; hyperkalemia equalled a potassium level of greater than 5.5 mEq/L.

In the spironolactone group, the rate of death was fairly stable – at about 17 per 100 patient-years – for patients with potassium levels ranging from 3.5 to 6.0 mEq/L. But it was higher among patients with lower levels (about 42 per 100 patient-years) or higher levels (about 25 per 100 patient-years).

In a multivariate analysis, patients were more likely to develop hypokalemia if they were black (hazard ratio, 2.0) or had a higher New York Heart Association functional class (HR, 1.5), whereas they were less likely if they had a higher baseline potassium level (HR, 0.25) or received spironolactone (HR, 0.36).

Patients were more likely to develop hyperkalemia if they received spironolactone (HR, 3.7), had a higher baseline potassium level (HR, 2.4), or had a history of diabetes (HR, 1.9).

Compared with placebo-treated patients having potassium levels of less than 5.0 mEq/L, spironolactone-treated patients with elevated potassium levels still had a significantly lower risk of death with potassium levels up to 5.5 mEq/L, and they had a nonsignificantly lower risk with levels up to about 6.0 mEq/L.

Dr. Vardeny reported having no relevant conflicts of interest. The RALES trial was sponsored by Searle, manufacturer of Aldactone.

SEATTLE – Patients with heart failure still benefit from spironolactone therapy even when they develop elevated potassium levels, a well-known and potentially life-threatening side effect of the medication, new data suggest.

Investigators led by Orly Vardeny, Pharm.D., conducted a secondary analysis of data from the RALES (Randomized Aldactone Evaluation Study) trial, in which more than 1,500 patients with heart failure were assigned to spironolactone (Aldactone) or placebo.

The spironolactone group had nearly quadruple the risk of hyperkalemia compared with the placebo group, she reported at the annual meeting of the Heart Failure Society of America. And hyperkalemia was indeed associated with a higher mortality rate.

But relative to their placebo-treated counterparts who did not have elevated potassium levels, spironolactone-treated patients who had elevated potassium levels, up to a serum potassium level of at least 5.5 mEq/L, were still less likely to die.

"The benefits of spironolactone are maintained in patients with mild to moderate hyperkalemia, and even in patients with potassium levels approaching 6.0 mEq/L," commented Dr. Vardeny, who is an associate professor of pharmacy at the University of Wisconsin in Madison.

"Our data argue for strategies that maintain spironolactone or aldosterone antagonist therapy even in the setting of mild to moderate hyperkalemia," she maintained.

"How many of these patients were on digoxin, and did you factor that into the analysis?" asked session comoderator Dr. Carl V. Leier of the Ohio State University Medical Center in Columbus.

Dr. Vardeny replied that analyses did not adjust for digoxin use, but they did adjust for age, estimated glomerular filtration rate, baseline potassium level, and diabetes.

"It seems that hypokalemia was more dangerous than hyperkalemia," commented attendee Dr. Edward Gilbert of the University of Utah in Salt Lake City. Might some of the benefit of spironolactone actually be related to reduced hypokalemia, he wondered.

"My personal bias is that there could be an association. This is really difficult to prove, only because potassium will vary so much, so the data will inform multiple categories of potassium," Dr. Vardeny replied. "But yes, we are investigating that as well."

The 1,663 patients in RALES had moderate to severe heart failure with a left ventricular ejection fraction of less than 35%, and were already receiving an angiotensin-converting enzyme inhibitor with or without a diuretic. They were randomized evenly to 25 mg of spironolactone daily, with optional titration up to 50 mg daily or placebo.

Serum potassium levels were monitored regularly. If patients developed hyperkalemia, investigators could reduce the dose of study medication but were encouraged to first adjust doses of other medications.

Main RALES results, previously reported, showed that spironolactone treatment was associated with a 30% reduction in the risk of all-cause mortality and a 35% reduction in the risk of hospitalization for worsening of heart failure (N. Engl. J. Med. 1999;341:709-17).

The new analysis showed that both treatment groups had mean potassium levels of 4.3 mEq/L at baseline. But levels increased within the first month in the spironolactone group and remained persistently higher than those in the placebo group, by 0.25 mEq/L on average, throughout the trial.

Relative to their peers in the placebo group, patients in the spironolactone group were significantly less likely to develop hypokalemia (6.5% vs. 16.2%) and more likely to develop hyperkalemia (14.5% vs. 4.2%), Dr. Vardeny reported. Hypokalemia was defined as a potassium level of less than 3.5 mEq/L; hyperkalemia equalled a potassium level of greater than 5.5 mEq/L.

In the spironolactone group, the rate of death was fairly stable – at about 17 per 100 patient-years – for patients with potassium levels ranging from 3.5 to 6.0 mEq/L. But it was higher among patients with lower levels (about 42 per 100 patient-years) or higher levels (about 25 per 100 patient-years).

In a multivariate analysis, patients were more likely to develop hypokalemia if they were black (hazard ratio, 2.0) or had a higher New York Heart Association functional class (HR, 1.5), whereas they were less likely if they had a higher baseline potassium level (HR, 0.25) or received spironolactone (HR, 0.36).

Patients were more likely to develop hyperkalemia if they received spironolactone (HR, 3.7), had a higher baseline potassium level (HR, 2.4), or had a history of diabetes (HR, 1.9).

Compared with placebo-treated patients having potassium levels of less than 5.0 mEq/L, spironolactone-treated patients with elevated potassium levels still had a significantly lower risk of death with potassium levels up to 5.5 mEq/L, and they had a nonsignificantly lower risk with levels up to about 6.0 mEq/L.

Dr. Vardeny reported having no relevant conflicts of interest. The RALES trial was sponsored by Searle, manufacturer of Aldactone.

SEATTLE – A brief cognitive biobehavioral intervention focused on preventing and managing depression reduces adverse outcomes of heart failure, according to results from a randomized trial reported at the annual meeting of the Heart Failure Society of America.

"A 6-week biobehavioral intervention in patients with heart failure really was successful in severing the link between depression and poor outcomes," according to the study’s lead investigator, Debra K. Moser, D.N.Sc., professor and chair of the College of Nursing at the University of Kentucky, Lexington. "These findings provide evidence for the effectiveness of biobehavioral approaches" in this population.

Dr. Moser also noted that more than one-fifth of patients with heart failure have depression, as well as higher depressive symptoms – not necessarily clinical depression. Evidence suggests that in the heart failure population, such symptoms triple the risk of rehospitalization and double the risk of death (J. Am. Coll. Cardiol. 2006;48:1527-37).

Dr. Moser and her colleagues studied 278 patients with heart failure, assigning them to a biobehavioral intervention group (given both cognitive-behavioral therapy and biofeedback-relaxation therapy), an attention control group, or a usual-care control group. At baseline, patients were an average of 60 years old, roughly a third were women, and nearly half had New York Heart Association class III or IV heart failure. Mean depression scores on the 27-point Patient Health Questionnaire-9 were about 5.5; one-fourth of patients were taking antidepressants. Patients with heart failure were eligible for the trial if they had been on stable medication doses for at least 1 month, had not experienced a myocardial infarction or stroke in the previous 3 months, and did not have any cognitive impairment.

At 12 months’ follow-up, the biobehavioral intervention patients were about one-third less likely to have had a cardiac hospitalization or to die (28%) compared with the attention control group (40%) and the usual-care control group (38%).

Patients in the biobehavioral intervention group also had an improvement at 1 year in scores for health-related quality of life, measured with the Minnesota Living with Heart Failure questionnaire, whereas scores worsened in the other groups (P = .005).

Similarly, patients in the biobehavioral intervention group had an improvement at 1 year in scores for depression symptoms, whereas scores worsened in the other groups (P = .001). Some 13% of patients in the biobehavioral intervention group had depression at this time point, compared with 21% of those in the attention control group and 24% of those in the usual-care control group.

The biobehavioral intervention lasted 6 weeks, and consisted of 1-hour weekly sessions conducted by a therapist; it was designed to address depression and comorbid anxiety. "The therapist was a psychiatric nurse practitioner with extensive cardiac experience, and she was well suited to this project because she is from the part of Kentucky where many of the patients come from, so ... there is a lot of concordance between her style and her patients’," Dr. Moser explained.

The attention control condition also lasted 6 weeks, and consisted of 1-hour weekly sessions with the same nurse practitioner present, but entailed only unguided relaxation and the opportunity to speak with her.

Christine Moravec, Ph.D., of the Cleveland Clinic, pointed out that at this point it’s difficult to dissect out whether the benefits seen in the biobehavioral intervention were due to the cognitive-behavioral therapy or the biofeedback.

"That’s our next trial" Dr. Moser noted. "We will be looking at the combination of the two and [each] separately."

Reproducibility is another issue, noted Dr. Javed Butler of Emory University in Atlanta. "Can anybody who does this biobehavioral intervention expect the same results?"

"That’s actually the major question that I have," Dr. Moser acknowledged. The particular nurse practitioner who ran the biobehavioral intervention "is probably the best therapist for these people that I have ever seen, so I really do worry about the reproducibility.

"But also, it sort of speaks to maybe some of the failure of the other clinical trials that we have seen in treating depression for cardiac patients. We have had some colossal failures," she continued. "I don’t think that any therapist can do it. It takes a special therapist who can really connect with patients, and a lot of patients, who can individualize therapy and is concordant with the group. ... The negative impact of depression is so powerful that it bears looking at to try to really define what it is in the therapist-patient relationship that is important and that does need to be reproduced."

Interestingly, depression levels in the biobehavioral intervention group continued to decline over a year, whereas they increased in the control groups, according to Dr. Moser. "We think that that is how cognitive-behavioral therapy should work. It doesn’t of course work for everyone, but if it works, it should give you the skills to manage depressive symptoms in the long term," she said.

"Future research should examine the combined effects of pharmacological and biobehavioral therapy, and ... we need to think about the practicality of this intensive intervention in widespread clinical practice," she added.

Dr. Moser reported having no relevant conflicts of interest.

SEATTLE – A brief cognitive biobehavioral intervention focused on preventing and managing depression reduces adverse outcomes of heart failure, according to results from a randomized trial reported at the annual meeting of the Heart Failure Society of America.

"A 6-week biobehavioral intervention in patients with heart failure really was successful in severing the link between depression and poor outcomes," according to the study’s lead investigator, Debra K. Moser, D.N.Sc., professor and chair of the College of Nursing at the University of Kentucky, Lexington. "These findings provide evidence for the effectiveness of biobehavioral approaches" in this population.

Dr. Moser also noted that more than one-fifth of patients with heart failure have depression, as well as higher depressive symptoms – not necessarily clinical depression. Evidence suggests that in the heart failure population, such symptoms triple the risk of rehospitalization and double the risk of death (J. Am. Coll. Cardiol. 2006;48:1527-37).

Dr. Moser and her colleagues studied 278 patients with heart failure, assigning them to a biobehavioral intervention group (given both cognitive-behavioral therapy and biofeedback-relaxation therapy), an attention control group, or a usual-care control group. At baseline, patients were an average of 60 years old, roughly a third were women, and nearly half had New York Heart Association class III or IV heart failure. Mean depression scores on the 27-point Patient Health Questionnaire-9 were about 5.5; one-fourth of patients were taking antidepressants. Patients with heart failure were eligible for the trial if they had been on stable medication doses for at least 1 month, had not experienced a myocardial infarction or stroke in the previous 3 months, and did not have any cognitive impairment.

At 12 months’ follow-up, the biobehavioral intervention patients were about one-third less likely to have had a cardiac hospitalization or to die (28%) compared with the attention control group (40%) and the usual-care control group (38%).

Patients in the biobehavioral intervention group also had an improvement at 1 year in scores for health-related quality of life, measured with the Minnesota Living with Heart Failure questionnaire, whereas scores worsened in the other groups (P = .005).

Similarly, patients in the biobehavioral intervention group had an improvement at 1 year in scores for depression symptoms, whereas scores worsened in the other groups (P = .001). Some 13% of patients in the biobehavioral intervention group had depression at this time point, compared with 21% of those in the attention control group and 24% of those in the usual-care control group.

The biobehavioral intervention lasted 6 weeks, and consisted of 1-hour weekly sessions conducted by a therapist; it was designed to address depression and comorbid anxiety. "The therapist was a psychiatric nurse practitioner with extensive cardiac experience, and she was well suited to this project because she is from the part of Kentucky where many of the patients come from, so ... there is a lot of concordance between her style and her patients’," Dr. Moser explained.

The attention control condition also lasted 6 weeks, and consisted of 1-hour weekly sessions with the same nurse practitioner present, but entailed only unguided relaxation and the opportunity to speak with her.

Christine Moravec, Ph.D., of the Cleveland Clinic, pointed out that at this point it’s difficult to dissect out whether the benefits seen in the biobehavioral intervention were due to the cognitive-behavioral therapy or the biofeedback.

"That’s our next trial" Dr. Moser noted. "We will be looking at the combination of the two and [each] separately."

Reproducibility is another issue, noted Dr. Javed Butler of Emory University in Atlanta. "Can anybody who does this biobehavioral intervention expect the same results?"

"That’s actually the major question that I have," Dr. Moser acknowledged. The particular nurse practitioner who ran the biobehavioral intervention "is probably the best therapist for these people that I have ever seen, so I really do worry about the reproducibility.

"But also, it sort of speaks to maybe some of the failure of the other clinical trials that we have seen in treating depression for cardiac patients. We have had some colossal failures," she continued. "I don’t think that any therapist can do it. It takes a special therapist who can really connect with patients, and a lot of patients, who can individualize therapy and is concordant with the group. ... The negative impact of depression is so powerful that it bears looking at to try to really define what it is in the therapist-patient relationship that is important and that does need to be reproduced."

Interestingly, depression levels in the biobehavioral intervention group continued to decline over a year, whereas they increased in the control groups, according to Dr. Moser. "We think that that is how cognitive-behavioral therapy should work. It doesn’t of course work for everyone, but if it works, it should give you the skills to manage depressive symptoms in the long term," she said.

"Future research should examine the combined effects of pharmacological and biobehavioral therapy, and ... we need to think about the practicality of this intensive intervention in widespread clinical practice," she added.

Dr. Moser reported having no relevant conflicts of interest.

SEATTLE – A brief cognitive biobehavioral intervention focused on preventing and managing depression reduces adverse outcomes of heart failure, according to results from a randomized trial reported at the annual meeting of the Heart Failure Society of America.

"A 6-week biobehavioral intervention in patients with heart failure really was successful in severing the link between depression and poor outcomes," according to the study’s lead investigator, Debra K. Moser, D.N.Sc., professor and chair of the College of Nursing at the University of Kentucky, Lexington. "These findings provide evidence for the effectiveness of biobehavioral approaches" in this population.

Dr. Moser also noted that more than one-fifth of patients with heart failure have depression, as well as higher depressive symptoms – not necessarily clinical depression. Evidence suggests that in the heart failure population, such symptoms triple the risk of rehospitalization and double the risk of death (J. Am. Coll. Cardiol. 2006;48:1527-37).

Dr. Moser and her colleagues studied 278 patients with heart failure, assigning them to a biobehavioral intervention group (given both cognitive-behavioral therapy and biofeedback-relaxation therapy), an attention control group, or a usual-care control group. At baseline, patients were an average of 60 years old, roughly a third were women, and nearly half had New York Heart Association class III or IV heart failure. Mean depression scores on the 27-point Patient Health Questionnaire-9 were about 5.5; one-fourth of patients were taking antidepressants. Patients with heart failure were eligible for the trial if they had been on stable medication doses for at least 1 month, had not experienced a myocardial infarction or stroke in the previous 3 months, and did not have any cognitive impairment.

At 12 months’ follow-up, the biobehavioral intervention patients were about one-third less likely to have had a cardiac hospitalization or to die (28%) compared with the attention control group (40%) and the usual-care control group (38%).

Patients in the biobehavioral intervention group also had an improvement at 1 year in scores for health-related quality of life, measured with the Minnesota Living with Heart Failure questionnaire, whereas scores worsened in the other groups (P = .005).

Similarly, patients in the biobehavioral intervention group had an improvement at 1 year in scores for depression symptoms, whereas scores worsened in the other groups (P = .001). Some 13% of patients in the biobehavioral intervention group had depression at this time point, compared with 21% of those in the attention control group and 24% of those in the usual-care control group.

The biobehavioral intervention lasted 6 weeks, and consisted of 1-hour weekly sessions conducted by a therapist; it was designed to address depression and comorbid anxiety. "The therapist was a psychiatric nurse practitioner with extensive cardiac experience, and she was well suited to this project because she is from the part of Kentucky where many of the patients come from, so ... there is a lot of concordance between her style and her patients’," Dr. Moser explained.

The attention control condition also lasted 6 weeks, and consisted of 1-hour weekly sessions with the same nurse practitioner present, but entailed only unguided relaxation and the opportunity to speak with her.

Christine Moravec, Ph.D., of the Cleveland Clinic, pointed out that at this point it’s difficult to dissect out whether the benefits seen in the biobehavioral intervention were due to the cognitive-behavioral therapy or the biofeedback.

"That’s our next trial" Dr. Moser noted. "We will be looking at the combination of the two and [each] separately."

Reproducibility is another issue, noted Dr. Javed Butler of Emory University in Atlanta. "Can anybody who does this biobehavioral intervention expect the same results?"

"That’s actually the major question that I have," Dr. Moser acknowledged. The particular nurse practitioner who ran the biobehavioral intervention "is probably the best therapist for these people that I have ever seen, so I really do worry about the reproducibility.

"But also, it sort of speaks to maybe some of the failure of the other clinical trials that we have seen in treating depression for cardiac patients. We have had some colossal failures," she continued. "I don’t think that any therapist can do it. It takes a special therapist who can really connect with patients, and a lot of patients, who can individualize therapy and is concordant with the group. ... The negative impact of depression is so powerful that it bears looking at to try to really define what it is in the therapist-patient relationship that is important and that does need to be reproduced."

Interestingly, depression levels in the biobehavioral intervention group continued to decline over a year, whereas they increased in the control groups, according to Dr. Moser. "We think that that is how cognitive-behavioral therapy should work. It doesn’t of course work for everyone, but if it works, it should give you the skills to manage depressive symptoms in the long term," she said.

"Future research should examine the combined effects of pharmacological and biobehavioral therapy, and ... we need to think about the practicality of this intensive intervention in widespread clinical practice," she added.

Dr. Moser reported having no relevant conflicts of interest.

MUNICH – Treatment with quinine increased the mortality of heart failure patients who also had ischemic heart disease and received a beta-blocker by a statistically significant 16% in a study of more than 136,000 Danish heart failure patients during 1997-2010.

Although experts suggest that such use of quinine is not commonplace in the United States, the analysis of Danish patient and population registries showed that quinine was used in the treatment of 10% of HF patients. Quinine, an antimalarial drug, is often prescribed off-label to treat leg cramps, a common problem in patients with HF, Dr. Charlotte Andersson said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/IMNG Medical Media

"Clinicians should attempt to find a treatment for leg cramps other than prescribing quinine" in patients with chronic HF, especially those with ischemic heart disease, said Dr. Andersson, a cardiologist at Gentofte Hospital in Copenhagen. She also expressed surprise that the dangerous interaction was greatest among patients who also received a beta-blocker drug.

"I would have expected patients on beta-blockers to be protected, but they weren’t, so probably conduction blocks [caused by quinine] are the problem," she said. "We found the highest risk of death during the first week of quinine treatment in patients with ischemic heart disease and on a beta-blocker, but if quinine was used chronically it still increased the risk."

"This is very interesting and important information," commented Dr. Marco Metra, a cardiologist at the University of Brescia, Italy. "The question is, what is the mechanism of the interaction of quinine and beta-blockers? We think that beta-blockers are protective against arrhythmias caused by QT prolongation. In this case, [the problem may be] bradycardia" caused by a beta-blocker that interacts with an effect from quinine, he suggested.

Dr. Andersson and her associates reviewed Danish national patient and population registry records collected during 1997-2010, which included 136,427 patients discharged from a hospital with a diagnosis of heart failure and who were alive at least 30 days following discharge. Their average age was 74 years, 47% were women, and 65% died during a median follow-up of 2.8 years.

The records showed that 14,306 patients (10%) had received at least one course of treatment with quinine, at a dosage of 100 or 200 mg/day. Overall, patients who received quinine had a 3% increased risk of death after adjustment for age and HF severity, which was estimated based on the dosage of loop diuretics they received. This increased risk fell just short of statistical significance.

However, further analysis showed that specific subgroups of HF patients faced a higher mortality threat from quinine treatment. Patients with ischemic heart disease (37% of the HF population) who received treatment with a beta-blocker (60% of the HF patients with ischemic heart disease) had the highest mortality when they received quinine, 16% higher than for similar patients who did not get quinine, after adjustment for age and HF severity. This meant that for every 38 patients with this clinical profile treated with quinine, 1 died.

Among HF patients with ischemic heart disease who did not receive a beta-blocker, the mortality rate was elevated by a statistically significant 8% among quinine users compared with quinine nonusers; 1 death occurred for every 46 patients in this category. And among HF patients who received a beta-blocker but who did not have ischemic heart disease, quinine treatment raised mortality by a statistically significant 9%, or 1 death for every 97 patients treated with quinine who fit this clinical profile.

Dr. Andersson said that she and her associates had no disclosures.

MUNICH – Treatment with quinine increased the mortality of heart failure patients who also had ischemic heart disease and received a beta-blocker by a statistically significant 16% in a study of more than 136,000 Danish heart failure patients during 1997-2010.

Although experts suggest that such use of quinine is not commonplace in the United States, the analysis of Danish patient and population registries showed that quinine was used in the treatment of 10% of HF patients. Quinine, an antimalarial drug, is often prescribed off-label to treat leg cramps, a common problem in patients with HF, Dr. Charlotte Andersson said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/IMNG Medical Media

"Clinicians should attempt to find a treatment for leg cramps other than prescribing quinine" in patients with chronic HF, especially those with ischemic heart disease, said Dr. Andersson, a cardiologist at Gentofte Hospital in Copenhagen. She also expressed surprise that the dangerous interaction was greatest among patients who also received a beta-blocker drug.

"I would have expected patients on beta-blockers to be protected, but they weren’t, so probably conduction blocks [caused by quinine] are the problem," she said. "We found the highest risk of death during the first week of quinine treatment in patients with ischemic heart disease and on a beta-blocker, but if quinine was used chronically it still increased the risk."

"This is very interesting and important information," commented Dr. Marco Metra, a cardiologist at the University of Brescia, Italy. "The question is, what is the mechanism of the interaction of quinine and beta-blockers? We think that beta-blockers are protective against arrhythmias caused by QT prolongation. In this case, [the problem may be] bradycardia" caused by a beta-blocker that interacts with an effect from quinine, he suggested.

Dr. Andersson and her associates reviewed Danish national patient and population registry records collected during 1997-2010, which included 136,427 patients discharged from a hospital with a diagnosis of heart failure and who were alive at least 30 days following discharge. Their average age was 74 years, 47% were women, and 65% died during a median follow-up of 2.8 years.

The records showed that 14,306 patients (10%) had received at least one course of treatment with quinine, at a dosage of 100 or 200 mg/day. Overall, patients who received quinine had a 3% increased risk of death after adjustment for age and HF severity, which was estimated based on the dosage of loop diuretics they received. This increased risk fell just short of statistical significance.

However, further analysis showed that specific subgroups of HF patients faced a higher mortality threat from quinine treatment. Patients with ischemic heart disease (37% of the HF population) who received treatment with a beta-blocker (60% of the HF patients with ischemic heart disease) had the highest mortality when they received quinine, 16% higher than for similar patients who did not get quinine, after adjustment for age and HF severity. This meant that for every 38 patients with this clinical profile treated with quinine, 1 died.

Among HF patients with ischemic heart disease who did not receive a beta-blocker, the mortality rate was elevated by a statistically significant 8% among quinine users compared with quinine nonusers; 1 death occurred for every 46 patients in this category. And among HF patients who received a beta-blocker but who did not have ischemic heart disease, quinine treatment raised mortality by a statistically significant 9%, or 1 death for every 97 patients treated with quinine who fit this clinical profile.

Dr. Andersson said that she and her associates had no disclosures.

MUNICH – Treatment with quinine increased the mortality of heart failure patients who also had ischemic heart disease and received a beta-blocker by a statistically significant 16% in a study of more than 136,000 Danish heart failure patients during 1997-2010.

Although experts suggest that such use of quinine is not commonplace in the United States, the analysis of Danish patient and population registries showed that quinine was used in the treatment of 10% of HF patients. Quinine, an antimalarial drug, is often prescribed off-label to treat leg cramps, a common problem in patients with HF, Dr. Charlotte Andersson said at the annual congress of the European Society of Cardiology.

Mitchel L. Zoler/IMNG Medical Media

"Clinicians should attempt to find a treatment for leg cramps other than prescribing quinine" in patients with chronic HF, especially those with ischemic heart disease, said Dr. Andersson, a cardiologist at Gentofte Hospital in Copenhagen. She also expressed surprise that the dangerous interaction was greatest among patients who also received a beta-blocker drug.

"I would have expected patients on beta-blockers to be protected, but they weren’t, so probably conduction blocks [caused by quinine] are the problem," she said. "We found the highest risk of death during the first week of quinine treatment in patients with ischemic heart disease and on a beta-blocker, but if quinine was used chronically it still increased the risk."

"This is very interesting and important information," commented Dr. Marco Metra, a cardiologist at the University of Brescia, Italy. "The question is, what is the mechanism of the interaction of quinine and beta-blockers? We think that beta-blockers are protective against arrhythmias caused by QT prolongation. In this case, [the problem may be] bradycardia" caused by a beta-blocker that interacts with an effect from quinine, he suggested.

Dr. Andersson and her associates reviewed Danish national patient and population registry records collected during 1997-2010, which included 136,427 patients discharged from a hospital with a diagnosis of heart failure and who were alive at least 30 days following discharge. Their average age was 74 years, 47% were women, and 65% died during a median follow-up of 2.8 years.

The records showed that 14,306 patients (10%) had received at least one course of treatment with quinine, at a dosage of 100 or 200 mg/day. Overall, patients who received quinine had a 3% increased risk of death after adjustment for age and HF severity, which was estimated based on the dosage of loop diuretics they received. This increased risk fell just short of statistical significance.

However, further analysis showed that specific subgroups of HF patients faced a higher mortality threat from quinine treatment. Patients with ischemic heart disease (37% of the HF population) who received treatment with a beta-blocker (60% of the HF patients with ischemic heart disease) had the highest mortality when they received quinine, 16% higher than for similar patients who did not get quinine, after adjustment for age and HF severity. This meant that for every 38 patients with this clinical profile treated with quinine, 1 died.

Among HF patients with ischemic heart disease who did not receive a beta-blocker, the mortality rate was elevated by a statistically significant 8% among quinine users compared with quinine nonusers; 1 death occurred for every 46 patients in this category. And among HF patients who received a beta-blocker but who did not have ischemic heart disease, quinine treatment raised mortality by a statistically significant 9%, or 1 death for every 97 patients treated with quinine who fit this clinical profile.

Dr. Andersson said that she and her associates had no disclosures.