Heart Failure

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote (J. Am. Coll. Cardiol. 2011;57:418-23).

“Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life,” wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, patients' mean age was 57 years; 70% were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Heart failure assessments included plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (LVEF, baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory (BDI) was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower LVEFs, and higher NT-proBNP levels, and were less likely to be taking nitrates. Aalysis showed that only NT-proBNP and LVEF were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

Significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) showed a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3-point or greater increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Those whose BDI was 3 points lower than baseline (indicating improvement in depression) showed a proportional risk reduction, compared with those with a change of 2 points or less (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure.

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O'Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

View on the News

Screen Heart Failure Patients for Depression

“The findings [of Dr. Sherwood and colleagues] raise additional questions,” about the relationship between depression and heart failure,” Ingrid Connerney, Ph.D., and Dr. Peter A. Shapiro wrote in an accompanying editorial (J. Am. Coll. Cardiol. 2011;57:424-6).

While this study noted that antidepressant use at baseline was not associated with an improvement in clinical outcomes, others have shown conflicting results. “Importantly, however, treatment of depression in patients with cardiac disease has been linked to at least modest reduction in depressive symptoms, improved quality of life, and improved adherence.”

The findings beg another question: Should cardiologists be screening heart failure patients for depression, or doing anything if they uncover it? The availability of a quick and easy-to-administer depression test points to yes, the authors said. “It is feasible for the cardiologist to assess patients regularly for depression. There are validated and brief screening instruments that can facilitate rapid identification of patients with depressive symptoms.”

One is as simple as asking two questions. “Over the past 2 weeks, have you been bothered by any of the following problems: 1) Feeling little interest or pleasure in doing things? 2) Feeling down, depressed or hopeless?”

If a patient answers yes to either one, the cardiologist might wish to further investigate, or refer the patient for treatment.

Finally, noted Dr. Connerney and Dr. Shapiro, there really is no way the study can answer the question of reverse causality. “Multiple physiological and behavioral mechanisms may underlie the association between depression and mortality,” they wrote. Further studies are needed of the relationship between the course of depression and mortality in heart failure patients, the mechanisms linking depression to adverse outcomes, and the effects of depression intervention.”

DR. CONNERNEY is the senior director of Quality, Safety, and Clinical Effectiveness at the University of Maryland Medical Center in Baltimore. DR. SHAPIRO is professor of clinical psychiatry at the New York Presbyterian Hospital–Columbia University Medical Center. Both reported that they had no relationships to disclose.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote (J. Am. Coll. Cardiol. 2011;57:418-23).

“Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life,” wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, patients' mean age was 57 years; 70% were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Heart failure assessments included plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (LVEF, baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory (BDI) was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower LVEFs, and higher NT-proBNP levels, and were less likely to be taking nitrates. Aalysis showed that only NT-proBNP and LVEF were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

Significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) showed a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3-point or greater increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Those whose BDI was 3 points lower than baseline (indicating improvement in depression) showed a proportional risk reduction, compared with those with a change of 2 points or less (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure.

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O'Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

View on the News

Screen Heart Failure Patients for Depression

“The findings [of Dr. Sherwood and colleagues] raise additional questions,” about the relationship between depression and heart failure,” Ingrid Connerney, Ph.D., and Dr. Peter A. Shapiro wrote in an accompanying editorial (J. Am. Coll. Cardiol. 2011;57:424-6).

While this study noted that antidepressant use at baseline was not associated with an improvement in clinical outcomes, others have shown conflicting results. “Importantly, however, treatment of depression in patients with cardiac disease has been linked to at least modest reduction in depressive symptoms, improved quality of life, and improved adherence.”

The findings beg another question: Should cardiologists be screening heart failure patients for depression, or doing anything if they uncover it? The availability of a quick and easy-to-administer depression test points to yes, the authors said. “It is feasible for the cardiologist to assess patients regularly for depression. There are validated and brief screening instruments that can facilitate rapid identification of patients with depressive symptoms.”

One is as simple as asking two questions. “Over the past 2 weeks, have you been bothered by any of the following problems: 1) Feeling little interest or pleasure in doing things? 2) Feeling down, depressed or hopeless?”

If a patient answers yes to either one, the cardiologist might wish to further investigate, or refer the patient for treatment.

Finally, noted Dr. Connerney and Dr. Shapiro, there really is no way the study can answer the question of reverse causality. “Multiple physiological and behavioral mechanisms may underlie the association between depression and mortality,” they wrote. Further studies are needed of the relationship between the course of depression and mortality in heart failure patients, the mechanisms linking depression to adverse outcomes, and the effects of depression intervention.”

DR. CONNERNEY is the senior director of Quality, Safety, and Clinical Effectiveness at the University of Maryland Medical Center in Baltimore. DR. SHAPIRO is professor of clinical psychiatry at the New York Presbyterian Hospital–Columbia University Medical Center. Both reported that they had no relationships to disclose.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote (J. Am. Coll. Cardiol. 2011;57:418-23).

“Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life,” wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, patients' mean age was 57 years; 70% were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Heart failure assessments included plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (LVEF, baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory (BDI) was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower LVEFs, and higher NT-proBNP levels, and were less likely to be taking nitrates. Aalysis showed that only NT-proBNP and LVEF were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

Significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) showed a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3-point or greater increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Those whose BDI was 3 points lower than baseline (indicating improvement in depression) showed a proportional risk reduction, compared with those with a change of 2 points or less (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure.

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O'Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

View on the News

Screen Heart Failure Patients for Depression

“The findings [of Dr. Sherwood and colleagues] raise additional questions,” about the relationship between depression and heart failure,” Ingrid Connerney, Ph.D., and Dr. Peter A. Shapiro wrote in an accompanying editorial (J. Am. Coll. Cardiol. 2011;57:424-6).

While this study noted that antidepressant use at baseline was not associated with an improvement in clinical outcomes, others have shown conflicting results. “Importantly, however, treatment of depression in patients with cardiac disease has been linked to at least modest reduction in depressive symptoms, improved quality of life, and improved adherence.”

The findings beg another question: Should cardiologists be screening heart failure patients for depression, or doing anything if they uncover it? The availability of a quick and easy-to-administer depression test points to yes, the authors said. “It is feasible for the cardiologist to assess patients regularly for depression. There are validated and brief screening instruments that can facilitate rapid identification of patients with depressive symptoms.”

One is as simple as asking two questions. “Over the past 2 weeks, have you been bothered by any of the following problems: 1) Feeling little interest or pleasure in doing things? 2) Feeling down, depressed or hopeless?”

If a patient answers yes to either one, the cardiologist might wish to further investigate, or refer the patient for treatment.

Finally, noted Dr. Connerney and Dr. Shapiro, there really is no way the study can answer the question of reverse causality. “Multiple physiological and behavioral mechanisms may underlie the association between depression and mortality,” they wrote. Further studies are needed of the relationship between the course of depression and mortality in heart failure patients, the mechanisms linking depression to adverse outcomes, and the effects of depression intervention.”

DR. CONNERNEY is the senior director of Quality, Safety, and Clinical Effectiveness at the University of Maryland Medical Center in Baltimore. DR. SHAPIRO is professor of clinical psychiatry at the New York Presbyterian Hospital–Columbia University Medical Center. Both reported that they had no relationships to disclose.

Twelve months of daily doses of omega-3 fatty acids resulted in substantial improvements in chronic heart failure, according to a randomized, placebo-controlled study of 133 patients with mild to moderate chronic heart failure caused by nonischemic dilated cardiomyopathy.

The study demonstrated improvements in left ventricular ejection fraction, peak oxygen uptake (VO₂), exercise duration, and New York Heart Association functional class among patients taking about 5 g of omega-3 polyunsaturated fatty acids (PUFAs) daily for 1 month followed by another 11 months of 2-g daily doses (J. Am. Coll. Cardiol. 2011;57 [doi:10.1016/j.jacc.2010.11.017]).

“These beneficial effects suggest that omega-3 PUFAs may favorably affect cardiac remodeling and the decline of myocardial function in patients with [heart failure (HF)] and may account for the reduction in cardiovascular hospitalizations and hospitalizations for HF observed in our study,” wrote Dr. Savina Nodari of the University of Brescia [Italy], and colleagues. Whether omega-3 PUFAs exert similar effects in patients with other types of HF or with more advanced HF remains to be verified, they added.

The study was funded by the University of Brescia, Brescia, Italy. One of the study's coauthors (Dr. Mihai Gheorghiade of Northwestern University, Chicago) acknowledged consulting for, and receiving travel funds from, a number of pharmaceutical and device manufacturers. The other coauthors stated that they had no conflicts.

Twelve months of daily doses of omega-3 fatty acids resulted in substantial improvements in chronic heart failure, according to a randomized, placebo-controlled study of 133 patients with mild to moderate chronic heart failure caused by nonischemic dilated cardiomyopathy.

The study demonstrated improvements in left ventricular ejection fraction, peak oxygen uptake (VO₂), exercise duration, and New York Heart Association functional class among patients taking about 5 g of omega-3 polyunsaturated fatty acids (PUFAs) daily for 1 month followed by another 11 months of 2-g daily doses (J. Am. Coll. Cardiol. 2011;57 [doi:10.1016/j.jacc.2010.11.017]).

“These beneficial effects suggest that omega-3 PUFAs may favorably affect cardiac remodeling and the decline of myocardial function in patients with [heart failure (HF)] and may account for the reduction in cardiovascular hospitalizations and hospitalizations for HF observed in our study,” wrote Dr. Savina Nodari of the University of Brescia [Italy], and colleagues. Whether omega-3 PUFAs exert similar effects in patients with other types of HF or with more advanced HF remains to be verified, they added.

The study was funded by the University of Brescia, Brescia, Italy. One of the study's coauthors (Dr. Mihai Gheorghiade of Northwestern University, Chicago) acknowledged consulting for, and receiving travel funds from, a number of pharmaceutical and device manufacturers. The other coauthors stated that they had no conflicts.

Twelve months of daily doses of omega-3 fatty acids resulted in substantial improvements in chronic heart failure, according to a randomized, placebo-controlled study of 133 patients with mild to moderate chronic heart failure caused by nonischemic dilated cardiomyopathy.

The study demonstrated improvements in left ventricular ejection fraction, peak oxygen uptake (VO₂), exercise duration, and New York Heart Association functional class among patients taking about 5 g of omega-3 polyunsaturated fatty acids (PUFAs) daily for 1 month followed by another 11 months of 2-g daily doses (J. Am. Coll. Cardiol. 2011;57 [doi:10.1016/j.jacc.2010.11.017]).

“These beneficial effects suggest that omega-3 PUFAs may favorably affect cardiac remodeling and the decline of myocardial function in patients with [heart failure (HF)] and may account for the reduction in cardiovascular hospitalizations and hospitalizations for HF observed in our study,” wrote Dr. Savina Nodari of the University of Brescia [Italy], and colleagues. Whether omega-3 PUFAs exert similar effects in patients with other types of HF or with more advanced HF remains to be verified, they added.

The study was funded by the University of Brescia, Brescia, Italy. One of the study's coauthors (Dr. Mihai Gheorghiade of Northwestern University, Chicago) acknowledged consulting for, and receiving travel funds from, a number of pharmaceutical and device manufacturers. The other coauthors stated that they had no conflicts.

CHICAGO — Two major new clinical trials have failed to show improved outcomes for home telemonitoring of patients with heart failure, prompting a critical reappraisal of this once-promising disease management strategy.

“I think this is an important moment in our understanding of the contribution of this novel intervention in the overall management of heart failure – and I think the weight of evidence demonstrates that it is noncontributory,” Dr. Clyde W. Yancy said following presentation of the two randomized trials at the meeting.

“Evidence-based, guideline-driven therapy is the standard of care and should always be our first priority in the treatment of heart failure. The benefit of telemonitoring that has been demonstrated to be present has always been less in the few randomized controlled trials than the cohort studies, and we've allowed hyperbole and excitement to guide our judgment, rather than evidence,” added Dr. Yancy, medical director of the Baylor Heart and Vascular Institute and chief of cardiothoracic transplantation at Baylor University Medical Center in Dallas.

One of the studies presented at the AHA meeting was the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) trial, a National Heart, Lung, and Blood Institute–funded study involving 1,653 U.S. patients enrolled less than a month after discharge for acute decompensated heart failure.

After 6 months of daily remote telemonitoring using the commercially popular Tel-Assurance system marketed by Pharos Innovations, death and rehospitalization rates in patients using the automated telephone monitoring system were similar to those in controls receiving usual care, reported Dr. Sarwat I. Chaudhry of Yale University, New Haven, Conn.

Similarly, the 2-year Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial, which enrolled 710 German patients with mild to moderate heart failure, failed to show that 24/7 access to remote telemonitoring improves all-cause mortality or heart failure hospitalization rates compared to usual care, according to Dr. Stefan D. Anker, professor of cardiology at Charite University Hospital, Berlin.

“There's no need to parse the data any further,” commented Dr. Yancy, a former AHA president. “There was no benefit seen in either of these well-designed clinical trials on outcomes that are important to patients with heart failure.”

The findings in these two definitive randomized trials underscore the limitations of meta-analyses based upon small studies with heterogeneous results, including a Cochrane Collaboration review published just a few months ago, he added. The Cochrane report, based upon 11 studies involving 2,710 patients, concluded that telemonitoring programs for patients with chronic heart failure reduced the risk of all-cause mortality by one-third and all-cause hospitalization by 21% (Cochrane Database Syst. Rev. Aug. 4, 2010;CD007228. Review).

Health systems are under mounting pressure to reduce hospital readmissions, pressure that will intensify under the Patient Protection and Affordable Care Act. In this regard, Dr. Yancy noted that his recent Google search of the terms “telemonitoring and heart failure” brought up 87,000 entries. The entire first page consisted of commercial advertisements for available systems.

“Every commercial application I opened had an implicit promise, almost a guarantee, of reduced costs and better outcomes for your patients with heart failure. We need to retard this kind of unbridled rush to a technology which, even though seemingly benign, is one that comes at a cost and is not proven to benefit our patients with heart failure,” he concluded.

Another discussant of the trials, Dr. Lynne Warner Stevenson, stressed that telemonitoring for heart failure isn't dead, but for it to be effective, the right physiologic variables related to fluid balance need to be monitored. What's being monitored now – changes in body weight and symptoms – are inadequate as harbingers of decompensation. They often occur too late for out-of-hospital correction. Ambulatory hemodynamic monitoring via implanted devices, now under study, holds more promise.

With more responsive physiologic measures and improved electronic technology, it should be possible for heart failure patients to monitor their disease status and adjust their own diuretic therapy without the labor-intense daily remote involvement of physicians and nurses required by today's telemonitoring systems, predicted Dr. Stevenson, professor of medicine at Harvard Medical School and director of the cardiomyopathy and heart failure program at Brigham and Women's Hospital, both in Boston.

“It has certainly been achieved for diabetic management. We never thought this would be possible, but most of our diabetic patients actually adjust their own medications several times a day according to their glucose readings,” she noted.

Dr. Chaudhry, Dr. Yancy, and Dr. Stevenson declared having no relevant financial interests. The TIM-HF trial was funded by the German Federal Ministry of Economics and Technology in partnership with several technology companies. Dr. Anker disclosed that he serves as a consultant to one of those companies, Robert Bosch Healthcare.

'There was no benefit seen in either [trial] on outcomes that are important to patients with heart failure.'

Source DR. YANCY

CHICAGO — Two major new clinical trials have failed to show improved outcomes for home telemonitoring of patients with heart failure, prompting a critical reappraisal of this once-promising disease management strategy.

“I think this is an important moment in our understanding of the contribution of this novel intervention in the overall management of heart failure – and I think the weight of evidence demonstrates that it is noncontributory,” Dr. Clyde W. Yancy said following presentation of the two randomized trials at the meeting.

“Evidence-based, guideline-driven therapy is the standard of care and should always be our first priority in the treatment of heart failure. The benefit of telemonitoring that has been demonstrated to be present has always been less in the few randomized controlled trials than the cohort studies, and we've allowed hyperbole and excitement to guide our judgment, rather than evidence,” added Dr. Yancy, medical director of the Baylor Heart and Vascular Institute and chief of cardiothoracic transplantation at Baylor University Medical Center in Dallas.

One of the studies presented at the AHA meeting was the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) trial, a National Heart, Lung, and Blood Institute–funded study involving 1,653 U.S. patients enrolled less than a month after discharge for acute decompensated heart failure.

After 6 months of daily remote telemonitoring using the commercially popular Tel-Assurance system marketed by Pharos Innovations, death and rehospitalization rates in patients using the automated telephone monitoring system were similar to those in controls receiving usual care, reported Dr. Sarwat I. Chaudhry of Yale University, New Haven, Conn.

Similarly, the 2-year Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial, which enrolled 710 German patients with mild to moderate heart failure, failed to show that 24/7 access to remote telemonitoring improves all-cause mortality or heart failure hospitalization rates compared to usual care, according to Dr. Stefan D. Anker, professor of cardiology at Charite University Hospital, Berlin.

“There's no need to parse the data any further,” commented Dr. Yancy, a former AHA president. “There was no benefit seen in either of these well-designed clinical trials on outcomes that are important to patients with heart failure.”

The findings in these two definitive randomized trials underscore the limitations of meta-analyses based upon small studies with heterogeneous results, including a Cochrane Collaboration review published just a few months ago, he added. The Cochrane report, based upon 11 studies involving 2,710 patients, concluded that telemonitoring programs for patients with chronic heart failure reduced the risk of all-cause mortality by one-third and all-cause hospitalization by 21% (Cochrane Database Syst. Rev. Aug. 4, 2010;CD007228. Review).

Health systems are under mounting pressure to reduce hospital readmissions, pressure that will intensify under the Patient Protection and Affordable Care Act. In this regard, Dr. Yancy noted that his recent Google search of the terms “telemonitoring and heart failure” brought up 87,000 entries. The entire first page consisted of commercial advertisements for available systems.

“Every commercial application I opened had an implicit promise, almost a guarantee, of reduced costs and better outcomes for your patients with heart failure. We need to retard this kind of unbridled rush to a technology which, even though seemingly benign, is one that comes at a cost and is not proven to benefit our patients with heart failure,” he concluded.

Another discussant of the trials, Dr. Lynne Warner Stevenson, stressed that telemonitoring for heart failure isn't dead, but for it to be effective, the right physiologic variables related to fluid balance need to be monitored. What's being monitored now – changes in body weight and symptoms – are inadequate as harbingers of decompensation. They often occur too late for out-of-hospital correction. Ambulatory hemodynamic monitoring via implanted devices, now under study, holds more promise.

With more responsive physiologic measures and improved electronic technology, it should be possible for heart failure patients to monitor their disease status and adjust their own diuretic therapy without the labor-intense daily remote involvement of physicians and nurses required by today's telemonitoring systems, predicted Dr. Stevenson, professor of medicine at Harvard Medical School and director of the cardiomyopathy and heart failure program at Brigham and Women's Hospital, both in Boston.

“It has certainly been achieved for diabetic management. We never thought this would be possible, but most of our diabetic patients actually adjust their own medications several times a day according to their glucose readings,” she noted.

Dr. Chaudhry, Dr. Yancy, and Dr. Stevenson declared having no relevant financial interests. The TIM-HF trial was funded by the German Federal Ministry of Economics and Technology in partnership with several technology companies. Dr. Anker disclosed that he serves as a consultant to one of those companies, Robert Bosch Healthcare.

'There was no benefit seen in either [trial] on outcomes that are important to patients with heart failure.'

Source DR. YANCY

CHICAGO — Two major new clinical trials have failed to show improved outcomes for home telemonitoring of patients with heart failure, prompting a critical reappraisal of this once-promising disease management strategy.

“I think this is an important moment in our understanding of the contribution of this novel intervention in the overall management of heart failure – and I think the weight of evidence demonstrates that it is noncontributory,” Dr. Clyde W. Yancy said following presentation of the two randomized trials at the meeting.

“Evidence-based, guideline-driven therapy is the standard of care and should always be our first priority in the treatment of heart failure. The benefit of telemonitoring that has been demonstrated to be present has always been less in the few randomized controlled trials than the cohort studies, and we've allowed hyperbole and excitement to guide our judgment, rather than evidence,” added Dr. Yancy, medical director of the Baylor Heart and Vascular Institute and chief of cardiothoracic transplantation at Baylor University Medical Center in Dallas.

One of the studies presented at the AHA meeting was the Telemonitoring to Improve Heart Failure Outcomes (Tele-HF) trial, a National Heart, Lung, and Blood Institute–funded study involving 1,653 U.S. patients enrolled less than a month after discharge for acute decompensated heart failure.

After 6 months of daily remote telemonitoring using the commercially popular Tel-Assurance system marketed by Pharos Innovations, death and rehospitalization rates in patients using the automated telephone monitoring system were similar to those in controls receiving usual care, reported Dr. Sarwat I. Chaudhry of Yale University, New Haven, Conn.

Similarly, the 2-year Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial, which enrolled 710 German patients with mild to moderate heart failure, failed to show that 24/7 access to remote telemonitoring improves all-cause mortality or heart failure hospitalization rates compared to usual care, according to Dr. Stefan D. Anker, professor of cardiology at Charite University Hospital, Berlin.

“There's no need to parse the data any further,” commented Dr. Yancy, a former AHA president. “There was no benefit seen in either of these well-designed clinical trials on outcomes that are important to patients with heart failure.”

The findings in these two definitive randomized trials underscore the limitations of meta-analyses based upon small studies with heterogeneous results, including a Cochrane Collaboration review published just a few months ago, he added. The Cochrane report, based upon 11 studies involving 2,710 patients, concluded that telemonitoring programs for patients with chronic heart failure reduced the risk of all-cause mortality by one-third and all-cause hospitalization by 21% (Cochrane Database Syst. Rev. Aug. 4, 2010;CD007228. Review).

Health systems are under mounting pressure to reduce hospital readmissions, pressure that will intensify under the Patient Protection and Affordable Care Act. In this regard, Dr. Yancy noted that his recent Google search of the terms “telemonitoring and heart failure” brought up 87,000 entries. The entire first page consisted of commercial advertisements for available systems.

“Every commercial application I opened had an implicit promise, almost a guarantee, of reduced costs and better outcomes for your patients with heart failure. We need to retard this kind of unbridled rush to a technology which, even though seemingly benign, is one that comes at a cost and is not proven to benefit our patients with heart failure,” he concluded.

Another discussant of the trials, Dr. Lynne Warner Stevenson, stressed that telemonitoring for heart failure isn't dead, but for it to be effective, the right physiologic variables related to fluid balance need to be monitored. What's being monitored now – changes in body weight and symptoms – are inadequate as harbingers of decompensation. They often occur too late for out-of-hospital correction. Ambulatory hemodynamic monitoring via implanted devices, now under study, holds more promise.

With more responsive physiologic measures and improved electronic technology, it should be possible for heart failure patients to monitor their disease status and adjust their own diuretic therapy without the labor-intense daily remote involvement of physicians and nurses required by today's telemonitoring systems, predicted Dr. Stevenson, professor of medicine at Harvard Medical School and director of the cardiomyopathy and heart failure program at Brigham and Women's Hospital, both in Boston.

“It has certainly been achieved for diabetic management. We never thought this would be possible, but most of our diabetic patients actually adjust their own medications several times a day according to their glucose readings,” she noted.

Dr. Chaudhry, Dr. Yancy, and Dr. Stevenson declared having no relevant financial interests. The TIM-HF trial was funded by the German Federal Ministry of Economics and Technology in partnership with several technology companies. Dr. Anker disclosed that he serves as a consultant to one of those companies, Robert Bosch Healthcare.

'There was no benefit seen in either [trial] on outcomes that are important to patients with heart failure.'

Source DR. YANCY

Major Finding: Community-dwelling older adults in the highest quartile for their serum cardiac troponin T level, as measured with a high-sensitivity assay, had a two- to threefold increased risk for new-onset heart failure and for cardiovascular death during a median follow-up of 12 years.

Data Source: The 4,221 unselected U.S. residents age 65 or older (median age of 71) enrolled in the Cardiovascular Health Study.

Disclosures: The study was partially funded by Roche Diagnostics, which markets a high-sensitivity cardiac troponin T assay. Dr. deFilippi said that he has served as a consultant to and has received honoraria and grant support from Roche Diagnostics and from Siemens Healthcare Diagnostics. He has also been a consultant to and received grant support from Critical Diagnostics and BG Medicine.

CHICAGO — Higher serum concentrations of cardiac troponin T independently predicted an increased rate of new-onset heart failure and cardiovascular death in a longitudinal study of more than 4,000 elderly, community-dwelling Americans with a median follow-up of 12 years.

“Measurement of cTnT [cardiac troponin T] may be useful in cardiovascular risk stratification in older adults,” Dr. Christopher R. deFilippi said at the scientific sessions.

Assessing cTnT's role as a risk predictor became possible with the recent availability of high-sensitivity assays. Previous studies using conventional cTnT assays found roughly 4% of the general elderly population had detectable levels; in Dr. deFilippi's new study, 66% of community-dwelling U.S. adults with a median age of 71 had detectable cTnT levels. The high-sensitivity test produces “about a 10-fold increase in the number of people with detectable cTnT; that's what gives us a dynamic range,” said Dr. deFilippi, a cardiologist at the University of Maryland in Baltimore.

Results from two other studies presented at the meeting and a third study published in early December showed similar links between high levels of cTnT and cardiovascular events, cardiac structure, and death (see box).

The consistent findings from all these studies show that cTnT “is a pretty good risk predictor. Cardiac troponin offers a very easy way for a physician to say that a person is at high risk” for new-onset heart failure, cardiovascular death, or other cardiovascular disease events, Dr. deFilippi said in an interview.

“I look at cardiac troponin T as early biochemical evidence of pathology. Finding a high level in a person could be a wake-up call. It gives some of the earliest, direct evidence with a cardiac-specific molecule that pathology is taking place,” independent of traditional risk markers, he said.

“Cardiac troponin T could be the summation of all other risk factors. We use cholesterol level as a motivator, even though it is much less effective for measuring risk,” Dr. deFilippi explained.

Another attractive feature of measuring cTnT is that the evidence collected by Dr. deFilippi and his associates suggest that in some people high levels are reversible, and when levels drop a person's risk drops.

In the analyses so far, the strongest correlation with a lowered serum level of cTnT has been a person's level of activity and exercise, he said.

The high-sensitivity cardiac troponin T test has not yet received marketing approval from the Food and Drug Administration, but is commercially available in Europe.

To examine the prognostic ability of cTnT, Dr. deFilippi and his associates used serum specimens collected from 4,221 community-dwelling Americans aged 65 or older enrolled in the Cardiovascular Health Study.

At baseline, 2,794 (66%) of the participants had a detectable level of cTnT, at least 3 pg/mL, and their median age was 71.

During a median follow-up of almost 12 years, the incidence of heart failure and cardiovascular death tracked along with baseline levels of cTnT. Among the one-third of patients with an undetectable level at baseline the rate of new-onset heart failure during follow-up averaged 1.6% per year. Among people in the highest quintile of cTnT level, greater than 12.9 pg/mL, the incident heart failure rate averaged 6.4% per year. “It's a huge difference,” he said.

In an analysis that adjusted for demographic differences and traditional risk factors including systolic blood pressure, smoking status, serum creatinine, and left ventricular size, people with baseline cTnT levels above the median all had a significantly increased risk for both end points.

The quintile of people with the highest cardiac troponin T level had a 2.5-fold increased risk of new-onset heart failure and a threefold increased risk of cardiovascular death compared with those who had an undetectable level at baseline.

Even when also adjusted for baseline levels of NT-pro brain natriuretic peptide and C-reactive protein, people in the highest quintile for baseline level had about a twofold higher rate of heart failure and cardiovascular death during follow-up, Dr. deFilippi reported.

Records on follow-up cTnT levels, measured 2-3 years after baseline in 86% of the study participants, showed that among those with a detectable cTnT level at baseline, nearly two-thirds stayed at about the same level, 22% increased by more than 50%, and 14% decreased by more than 50%.

The high increasers had their subsequent heart failure and cardiovascular death rates rise by about 50% compared with people with more moderate changes.

In contrast, among those whose levels fell by more than 50% during follow-up subsequent event rates dropped by about 25% compared with those with less change in their cTnT level.

Concurrent with Dr. deFilippi's talk at the meeting the findings also appeared in an article published online in JAMA (2010; 304:doi:10.1001/jama.2010.1708).

The results also identified some people with very high levels at baseline that then fell to an undetectable level at their second cTnT measurement. Few people showed this kind of change, but it occurred often enough for Dr. deFilippi to speculate that certain actions can effectively lower serum cardiac troponin T levels.

The source of the cTnT isn't clear. Dr. deFilippi believes it's caused by a chronic process, although the specifics remain unknown. “It's unlikely an ischemic cause,” he said. “The issue is, once you see [a high level] can you intervene? Right now, that's an open question.”

Over 12 years, the rates of heart failure and cardiac death tracked along with baseline cTnT levels.

Source DR. DEFILIPPI

Other Studies Using High-Sensitivity Test Support cTnT's Risk-Marker Role

CHICAGO – In addition to the report by Dr. deFilippi, three other research groups recently reported finding significant links between elevated serum levels of cardiac troponin T and an increased risk for cardiovascular events:

▸ Researchers measured cardiac troponin T (cTnT) using a high-sensitivity assay in 10,820 Americans aged 53-75 without prevalent cardiovascular disease enrolled in the Atherosclerosis Risk in Communities (ARIC) study. In these people, with an average age of 63 years, 61% had a detectable level of serum cTnT at baseline using the high-sensitivity test. During an average follow-up of 10 years, Researchers found a significant link between detectable levels at baseline and death and hospitalization for heart failure during follow-up, Dr. Justin T. Saunders from Baylor College of Medicine in Houston reported at the scientific sessions.

▸ In a second, independent study, researchers measured serum cTnT with the high-sensitivity assay in women enrolled in the Women's Health Study. The current analysis focused on 512 women with diabetes at the time of their serum sampling and 564 women without diabetes. Among the women with diabetes, detectable levels of cTnT excisted in 56% of those who had cardiovascular disease events during follow-up and in 42% of the women who did not later have an event, a statistically significant difference. The event that seemed most responsible for this difference was cardiovascular disease death. Among the women without diabetes, detectable levels of cTnT appeared to have no significant relationship to subsequent cardiovascular disease events. Detectable cTnT appeared in 34% of the women with a subsequent event and in 30% of those without a later event, Dr. Brendan M. Everett from Brigham and Women's Hospital in Boston reported at the scientific sessions.

▸ In the third study, researchers ran high-sensitivity cTnT measures on 3,546 people aged 30-65 enrolled in the Dallas Heart Study. They found detectable levels in 25% of the participants. The prevalence of detectable levels depended on age and gender. People younger than 40 had a prevalence rate of 14% compared with a prevalence of 58% in people aged 65 or older. Men had a prevalence rate of 37%, compared with a rate of 13% in women. During a median follow-up of 6.4 years, in an analysis that adjusted for a series of baseline variables and risk factors, people in the highest quintile for serum cTnT level had a statistically significant, greater than fourfold increased risk for both all-cause death and cardiovascular death, said Dr. James A. de Lemos, from the University of Texas Southwestern Medical Center, and his associates in a report published in the Dec. 8, 2010, issue of JAMA (2010;304:2503-12).

Dr. Saunders had no disclosures.

Dr. Everett said he had received research grants from Roche Diagnostics.

Dr. de Lemos said that he has received research grants from Roche Diagnostics and Biosite, and consulting fees, lecture honoraria, or both from Tethys Biomedical, Johnson & Johnson, Roche Diagnostics, Biosite/Invemess, Siemens, AstraZeneca, Pfizer, Bristol Myers Squibb/Sanofi Aventis, and Merck.

– Mitchel L. Zoler

Major Finding: Community-dwelling older adults in the highest quartile for their serum cardiac troponin T level, as measured with a high-sensitivity assay, had a two- to threefold increased risk for new-onset heart failure and for cardiovascular death during a median follow-up of 12 years.

Data Source: The 4,221 unselected U.S. residents age 65 or older (median age of 71) enrolled in the Cardiovascular Health Study.

Disclosures: The study was partially funded by Roche Diagnostics, which markets a high-sensitivity cardiac troponin T assay. Dr. deFilippi said that he has served as a consultant to and has received honoraria and grant support from Roche Diagnostics and from Siemens Healthcare Diagnostics. He has also been a consultant to and received grant support from Critical Diagnostics and BG Medicine.

CHICAGO — Higher serum concentrations of cardiac troponin T independently predicted an increased rate of new-onset heart failure and cardiovascular death in a longitudinal study of more than 4,000 elderly, community-dwelling Americans with a median follow-up of 12 years.

“Measurement of cTnT [cardiac troponin T] may be useful in cardiovascular risk stratification in older adults,” Dr. Christopher R. deFilippi said at the scientific sessions.

Assessing cTnT's role as a risk predictor became possible with the recent availability of high-sensitivity assays. Previous studies using conventional cTnT assays found roughly 4% of the general elderly population had detectable levels; in Dr. deFilippi's new study, 66% of community-dwelling U.S. adults with a median age of 71 had detectable cTnT levels. The high-sensitivity test produces “about a 10-fold increase in the number of people with detectable cTnT; that's what gives us a dynamic range,” said Dr. deFilippi, a cardiologist at the University of Maryland in Baltimore.

Results from two other studies presented at the meeting and a third study published in early December showed similar links between high levels of cTnT and cardiovascular events, cardiac structure, and death (see box).

The consistent findings from all these studies show that cTnT “is a pretty good risk predictor. Cardiac troponin offers a very easy way for a physician to say that a person is at high risk” for new-onset heart failure, cardiovascular death, or other cardiovascular disease events, Dr. deFilippi said in an interview.

“I look at cardiac troponin T as early biochemical evidence of pathology. Finding a high level in a person could be a wake-up call. It gives some of the earliest, direct evidence with a cardiac-specific molecule that pathology is taking place,” independent of traditional risk markers, he said.

“Cardiac troponin T could be the summation of all other risk factors. We use cholesterol level as a motivator, even though it is much less effective for measuring risk,” Dr. deFilippi explained.

Another attractive feature of measuring cTnT is that the evidence collected by Dr. deFilippi and his associates suggest that in some people high levels are reversible, and when levels drop a person's risk drops.

In the analyses so far, the strongest correlation with a lowered serum level of cTnT has been a person's level of activity and exercise, he said.

The high-sensitivity cardiac troponin T test has not yet received marketing approval from the Food and Drug Administration, but is commercially available in Europe.

To examine the prognostic ability of cTnT, Dr. deFilippi and his associates used serum specimens collected from 4,221 community-dwelling Americans aged 65 or older enrolled in the Cardiovascular Health Study.

At baseline, 2,794 (66%) of the participants had a detectable level of cTnT, at least 3 pg/mL, and their median age was 71.

During a median follow-up of almost 12 years, the incidence of heart failure and cardiovascular death tracked along with baseline levels of cTnT. Among the one-third of patients with an undetectable level at baseline the rate of new-onset heart failure during follow-up averaged 1.6% per year. Among people in the highest quintile of cTnT level, greater than 12.9 pg/mL, the incident heart failure rate averaged 6.4% per year. “It's a huge difference,” he said.

In an analysis that adjusted for demographic differences and traditional risk factors including systolic blood pressure, smoking status, serum creatinine, and left ventricular size, people with baseline cTnT levels above the median all had a significantly increased risk for both end points.

The quintile of people with the highest cardiac troponin T level had a 2.5-fold increased risk of new-onset heart failure and a threefold increased risk of cardiovascular death compared with those who had an undetectable level at baseline.

Even when also adjusted for baseline levels of NT-pro brain natriuretic peptide and C-reactive protein, people in the highest quintile for baseline level had about a twofold higher rate of heart failure and cardiovascular death during follow-up, Dr. deFilippi reported.

Records on follow-up cTnT levels, measured 2-3 years after baseline in 86% of the study participants, showed that among those with a detectable cTnT level at baseline, nearly two-thirds stayed at about the same level, 22% increased by more than 50%, and 14% decreased by more than 50%.

The high increasers had their subsequent heart failure and cardiovascular death rates rise by about 50% compared with people with more moderate changes.

In contrast, among those whose levels fell by more than 50% during follow-up subsequent event rates dropped by about 25% compared with those with less change in their cTnT level.

Concurrent with Dr. deFilippi's talk at the meeting the findings also appeared in an article published online in JAMA (2010; 304:doi:10.1001/jama.2010.1708).

The results also identified some people with very high levels at baseline that then fell to an undetectable level at their second cTnT measurement. Few people showed this kind of change, but it occurred often enough for Dr. deFilippi to speculate that certain actions can effectively lower serum cardiac troponin T levels.

The source of the cTnT isn't clear. Dr. deFilippi believes it's caused by a chronic process, although the specifics remain unknown. “It's unlikely an ischemic cause,” he said. “The issue is, once you see [a high level] can you intervene? Right now, that's an open question.”

Over 12 years, the rates of heart failure and cardiac death tracked along with baseline cTnT levels.

Source DR. DEFILIPPI

Other Studies Using High-Sensitivity Test Support cTnT's Risk-Marker Role

CHICAGO – In addition to the report by Dr. deFilippi, three other research groups recently reported finding significant links between elevated serum levels of cardiac troponin T and an increased risk for cardiovascular events:

▸ Researchers measured cardiac troponin T (cTnT) using a high-sensitivity assay in 10,820 Americans aged 53-75 without prevalent cardiovascular disease enrolled in the Atherosclerosis Risk in Communities (ARIC) study. In these people, with an average age of 63 years, 61% had a detectable level of serum cTnT at baseline using the high-sensitivity test. During an average follow-up of 10 years, Researchers found a significant link between detectable levels at baseline and death and hospitalization for heart failure during follow-up, Dr. Justin T. Saunders from Baylor College of Medicine in Houston reported at the scientific sessions.

▸ In a second, independent study, researchers measured serum cTnT with the high-sensitivity assay in women enrolled in the Women's Health Study. The current analysis focused on 512 women with diabetes at the time of their serum sampling and 564 women without diabetes. Among the women with diabetes, detectable levels of cTnT excisted in 56% of those who had cardiovascular disease events during follow-up and in 42% of the women who did not later have an event, a statistically significant difference. The event that seemed most responsible for this difference was cardiovascular disease death. Among the women without diabetes, detectable levels of cTnT appeared to have no significant relationship to subsequent cardiovascular disease events. Detectable cTnT appeared in 34% of the women with a subsequent event and in 30% of those without a later event, Dr. Brendan M. Everett from Brigham and Women's Hospital in Boston reported at the scientific sessions.

▸ In the third study, researchers ran high-sensitivity cTnT measures on 3,546 people aged 30-65 enrolled in the Dallas Heart Study. They found detectable levels in 25% of the participants. The prevalence of detectable levels depended on age and gender. People younger than 40 had a prevalence rate of 14% compared with a prevalence of 58% in people aged 65 or older. Men had a prevalence rate of 37%, compared with a rate of 13% in women. During a median follow-up of 6.4 years, in an analysis that adjusted for a series of baseline variables and risk factors, people in the highest quintile for serum cTnT level had a statistically significant, greater than fourfold increased risk for both all-cause death and cardiovascular death, said Dr. James A. de Lemos, from the University of Texas Southwestern Medical Center, and his associates in a report published in the Dec. 8, 2010, issue of JAMA (2010;304:2503-12).

Dr. Saunders had no disclosures.

Dr. Everett said he had received research grants from Roche Diagnostics.

Dr. de Lemos said that he has received research grants from Roche Diagnostics and Biosite, and consulting fees, lecture honoraria, or both from Tethys Biomedical, Johnson & Johnson, Roche Diagnostics, Biosite/Invemess, Siemens, AstraZeneca, Pfizer, Bristol Myers Squibb/Sanofi Aventis, and Merck.

– Mitchel L. Zoler

Major Finding: Community-dwelling older adults in the highest quartile for their serum cardiac troponin T level, as measured with a high-sensitivity assay, had a two- to threefold increased risk for new-onset heart failure and for cardiovascular death during a median follow-up of 12 years.

Data Source: The 4,221 unselected U.S. residents age 65 or older (median age of 71) enrolled in the Cardiovascular Health Study.

Disclosures: The study was partially funded by Roche Diagnostics, which markets a high-sensitivity cardiac troponin T assay. Dr. deFilippi said that he has served as a consultant to and has received honoraria and grant support from Roche Diagnostics and from Siemens Healthcare Diagnostics. He has also been a consultant to and received grant support from Critical Diagnostics and BG Medicine.

CHICAGO — Higher serum concentrations of cardiac troponin T independently predicted an increased rate of new-onset heart failure and cardiovascular death in a longitudinal study of more than 4,000 elderly, community-dwelling Americans with a median follow-up of 12 years.

“Measurement of cTnT [cardiac troponin T] may be useful in cardiovascular risk stratification in older adults,” Dr. Christopher R. deFilippi said at the scientific sessions.

Assessing cTnT's role as a risk predictor became possible with the recent availability of high-sensitivity assays. Previous studies using conventional cTnT assays found roughly 4% of the general elderly population had detectable levels; in Dr. deFilippi's new study, 66% of community-dwelling U.S. adults with a median age of 71 had detectable cTnT levels. The high-sensitivity test produces “about a 10-fold increase in the number of people with detectable cTnT; that's what gives us a dynamic range,” said Dr. deFilippi, a cardiologist at the University of Maryland in Baltimore.

Results from two other studies presented at the meeting and a third study published in early December showed similar links between high levels of cTnT and cardiovascular events, cardiac structure, and death (see box).

The consistent findings from all these studies show that cTnT “is a pretty good risk predictor. Cardiac troponin offers a very easy way for a physician to say that a person is at high risk” for new-onset heart failure, cardiovascular death, or other cardiovascular disease events, Dr. deFilippi said in an interview.

“I look at cardiac troponin T as early biochemical evidence of pathology. Finding a high level in a person could be a wake-up call. It gives some of the earliest, direct evidence with a cardiac-specific molecule that pathology is taking place,” independent of traditional risk markers, he said.

“Cardiac troponin T could be the summation of all other risk factors. We use cholesterol level as a motivator, even though it is much less effective for measuring risk,” Dr. deFilippi explained.

Another attractive feature of measuring cTnT is that the evidence collected by Dr. deFilippi and his associates suggest that in some people high levels are reversible, and when levels drop a person's risk drops.

In the analyses so far, the strongest correlation with a lowered serum level of cTnT has been a person's level of activity and exercise, he said.

The high-sensitivity cardiac troponin T test has not yet received marketing approval from the Food and Drug Administration, but is commercially available in Europe.

To examine the prognostic ability of cTnT, Dr. deFilippi and his associates used serum specimens collected from 4,221 community-dwelling Americans aged 65 or older enrolled in the Cardiovascular Health Study.

At baseline, 2,794 (66%) of the participants had a detectable level of cTnT, at least 3 pg/mL, and their median age was 71.

During a median follow-up of almost 12 years, the incidence of heart failure and cardiovascular death tracked along with baseline levels of cTnT. Among the one-third of patients with an undetectable level at baseline the rate of new-onset heart failure during follow-up averaged 1.6% per year. Among people in the highest quintile of cTnT level, greater than 12.9 pg/mL, the incident heart failure rate averaged 6.4% per year. “It's a huge difference,” he said.

In an analysis that adjusted for demographic differences and traditional risk factors including systolic blood pressure, smoking status, serum creatinine, and left ventricular size, people with baseline cTnT levels above the median all had a significantly increased risk for both end points.

The quintile of people with the highest cardiac troponin T level had a 2.5-fold increased risk of new-onset heart failure and a threefold increased risk of cardiovascular death compared with those who had an undetectable level at baseline.

Even when also adjusted for baseline levels of NT-pro brain natriuretic peptide and C-reactive protein, people in the highest quintile for baseline level had about a twofold higher rate of heart failure and cardiovascular death during follow-up, Dr. deFilippi reported.

Records on follow-up cTnT levels, measured 2-3 years after baseline in 86% of the study participants, showed that among those with a detectable cTnT level at baseline, nearly two-thirds stayed at about the same level, 22% increased by more than 50%, and 14% decreased by more than 50%.

The high increasers had their subsequent heart failure and cardiovascular death rates rise by about 50% compared with people with more moderate changes.

In contrast, among those whose levels fell by more than 50% during follow-up subsequent event rates dropped by about 25% compared with those with less change in their cTnT level.

Concurrent with Dr. deFilippi's talk at the meeting the findings also appeared in an article published online in JAMA (2010; 304:doi:10.1001/jama.2010.1708).

The results also identified some people with very high levels at baseline that then fell to an undetectable level at their second cTnT measurement. Few people showed this kind of change, but it occurred often enough for Dr. deFilippi to speculate that certain actions can effectively lower serum cardiac troponin T levels.

The source of the cTnT isn't clear. Dr. deFilippi believes it's caused by a chronic process, although the specifics remain unknown. “It's unlikely an ischemic cause,” he said. “The issue is, once you see [a high level] can you intervene? Right now, that's an open question.”

Over 12 years, the rates of heart failure and cardiac death tracked along with baseline cTnT levels.

Source DR. DEFILIPPI

Other Studies Using High-Sensitivity Test Support cTnT's Risk-Marker Role

CHICAGO – In addition to the report by Dr. deFilippi, three other research groups recently reported finding significant links between elevated serum levels of cardiac troponin T and an increased risk for cardiovascular events:

▸ Researchers measured cardiac troponin T (cTnT) using a high-sensitivity assay in 10,820 Americans aged 53-75 without prevalent cardiovascular disease enrolled in the Atherosclerosis Risk in Communities (ARIC) study. In these people, with an average age of 63 years, 61% had a detectable level of serum cTnT at baseline using the high-sensitivity test. During an average follow-up of 10 years, Researchers found a significant link between detectable levels at baseline and death and hospitalization for heart failure during follow-up, Dr. Justin T. Saunders from Baylor College of Medicine in Houston reported at the scientific sessions.

▸ In a second, independent study, researchers measured serum cTnT with the high-sensitivity assay in women enrolled in the Women's Health Study. The current analysis focused on 512 women with diabetes at the time of their serum sampling and 564 women without diabetes. Among the women with diabetes, detectable levels of cTnT excisted in 56% of those who had cardiovascular disease events during follow-up and in 42% of the women who did not later have an event, a statistically significant difference. The event that seemed most responsible for this difference was cardiovascular disease death. Among the women without diabetes, detectable levels of cTnT appeared to have no significant relationship to subsequent cardiovascular disease events. Detectable cTnT appeared in 34% of the women with a subsequent event and in 30% of those without a later event, Dr. Brendan M. Everett from Brigham and Women's Hospital in Boston reported at the scientific sessions.

▸ In the third study, researchers ran high-sensitivity cTnT measures on 3,546 people aged 30-65 enrolled in the Dallas Heart Study. They found detectable levels in 25% of the participants. The prevalence of detectable levels depended on age and gender. People younger than 40 had a prevalence rate of 14% compared with a prevalence of 58% in people aged 65 or older. Men had a prevalence rate of 37%, compared with a rate of 13% in women. During a median follow-up of 6.4 years, in an analysis that adjusted for a series of baseline variables and risk factors, people in the highest quintile for serum cTnT level had a statistically significant, greater than fourfold increased risk for both all-cause death and cardiovascular death, said Dr. James A. de Lemos, from the University of Texas Southwestern Medical Center, and his associates in a report published in the Dec. 8, 2010, issue of JAMA (2010;304:2503-12).

Dr. Saunders had no disclosures.

Dr. Everett said he had received research grants from Roche Diagnostics.

Dr. de Lemos said that he has received research grants from Roche Diagnostics and Biosite, and consulting fees, lecture honoraria, or both from Tethys Biomedical, Johnson & Johnson, Roche Diagnostics, Biosite/Invemess, Siemens, AstraZeneca, Pfizer, Bristol Myers Squibb/Sanofi Aventis, and Merck.

– Mitchel L. Zoler

Major Finding: Addition of CRT to an ICD significantly reduced the rate of death and heart failure hospitalization by 25% in patients with NYHA class II or III heart failure.

Data Source: Randomized trial in 1,798 patients with mild to moderate heart failure.

Disclosures: RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Medtronic, St. Jude Medical, and Boston Scientific. Dr. Yancy said he had no financial conflicts of interest.

CHICAGO – for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas and immediate past president of the AHA.

He observed that a suite of randomized trials, including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients that have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009;361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

The RAFT data were simultaneously published online by the New England Journal of Medicine (2010;10.1056/NEJM0a1009540).

Major Finding: Addition of CRT to an ICD significantly reduced the rate of death and heart failure hospitalization by 25% in patients with NYHA class II or III heart failure.

Data Source: Randomized trial in 1,798 patients with mild to moderate heart failure.

Disclosures: RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Medtronic, St. Jude Medical, and Boston Scientific. Dr. Yancy said he had no financial conflicts of interest.

CHICAGO – for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas and immediate past president of the AHA.

He observed that a suite of randomized trials, including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients that have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009;361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

The RAFT data were simultaneously published online by the New England Journal of Medicine (2010;10.1056/NEJM0a1009540).

Major Finding: Addition of CRT to an ICD significantly reduced the rate of death and heart failure hospitalization by 25% in patients with NYHA class II or III heart failure.

Data Source: Randomized trial in 1,798 patients with mild to moderate heart failure.

Disclosures: RAFT was funded by the Canadian Institutes of Health Research and Medtronic of Canada. Dr. Tang disclosed research support from Medtronic, St. Jude Medical, and Boston Scientific. Dr. Yancy said he had no financial conflicts of interest.

CHICAGO – for the first time, cardiac resynchronization therapy has been shown to offer a survival benefit beyond that provided by an implantable cardioverter defibrillator in patients with mild heart failure, a study has shown.

The addition of cardiac resynchronization therapy (CRT) to an implantable cardioverter defibrillator (ICD) and optimal medical therapy significantly reduced the rates of death and heart failure hospitalization from 40% with an ICD alone to 33% in the multicenter Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT).

The relative risk of death was reduced by 25% among patients who received CRT plus ICD, resulting in an absolute mortality reduction of 6% at 5 years, Dr. Anthony Tang reported at the meeting. Fourteen patients would need to be treated with CRT plus ICD for 5 years to prevent one death.

Significantly fewer CRT-ICD patients were hospitalized for heart failure (19.5%, or 174/894) than ICD-only patients (26%, or 236/904). This meant that 11 patients would need to be treated with CRT plus ICD for 5 years to prevent one heart failure hospitalization, said Dr. Tang, professor of medicine at the University of British Columbia, Vancouver.

RAFT enrolled 1,798 patients (mean age, 66 years), who had New York Heart Association class II or III heart failure, a left ventricular ejection fraction (LVEF) of 30% or less, and a wide QRS duration of at least 120 milliseconds or a paced QRS duration of at least 200 milliseconds.

CRT with or without an ICD is currently indicated only for the treatment of patients with NYHA functional class III or ambulatory class IV heart failure.

The data are likely to change clinical practice, said invited discussant Dr. Clyde W. Yancy, medical director of Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas and immediate past president of the AHA.

He observed that a suite of randomized trials, including COMPANION, CARE-HF, MADIT-CRT, REVERSE, and now RAFT demonstrate compellingly that CRT is effective in heart failure.

“The benefit can now be extended to patients that have mild heart failure,” he said.

In the pivotal Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT), however, the use of CRT-ICD therapy decreased the risk of heart failure events but not the risk of death among NYHA class I or II patients with an ejection fraction of 30% or less and a QRS duration of 130 milliseconds or more (N. Engl. J. Med. 2009;361:1329-38).

Dr. Yancy observed that CRT plus ICD is used in only about one-third of heart failure patients and suggested that its limited uptake is due to persistent equipoise, postprocedural risks that are not insignificant, an early failure rate of about 5% and a late failure rate of up to 25%, imprecise markers of clinical response, and current guidelines.

The improved outcomes, however, did come at the cost of increased adverse events. Within 30 days of device implantation, significantly more CRT-ICD patients than ICD-alone patients had lead dislodgment (61 vs. 20 patients) and coronary sinus dissection (11 vs. 0), Dr. Tang reported. The CRT-ICD and ICD-alone groups had similar rates of hemothorax or pneumothorax (11 vs. 8 patients), pocket hematoma (14 vs. 11), pocket infection (21 vs. 16), tamponade (1 vs. 2), and device pocket revision (4 vs. 1).

An analysis by NYHA class showed that the majority of positive results held true, Dr. Tang said. The primary composite end point was significantly improved in both NYHA class II and III patients, while death from any cause was significantly improved among class II, but not class III patients.

The RAFT data were simultaneously published online by the New England Journal of Medicine (2010;10.1056/NEJM0a1009540).

STOCKHOLM – Suboptimal glycemic control is an independent risk factor for a linear increase in the rate of new-onset heart failure in patients with type 2 diabetes, a large Scottish prospective case-control study indicates.

Moreover, in type 2 diabetes patients who already have established heart failure, poor glycemic control is independently associated with increased mortality, Dr. Chim Choy Lang reported at the congress.

These were the key findings in a new analysis from the Tayside Study, which is directed by Dr. Lang. The ongoing project provides an unusual opportunity to prospectively follow an entire Scottish community, population 400,000.

“We can track patients with diabetes mellitus, looking at mean [hemoglobin A_1c] over time, and see who develops heart failure,” Dr. Lang said in an interview.

“Our bioinformatics platform allows us to track all sorts of biologic variables, prescribing information, and outcomes data,” he explained.

The analysis of Tayside Study data was performed because controversy has arisen surrounding the relationship between glycemic control in type 2 diabetes and heart failure.

Some recent evidence has suggested that tight metabolic control in type 2 diabetes is actually associated with worse survival of patients in the setting of heart failure.

“It should be noted that most of these studies were based on a single measure of HbA_1c,” observed Dr. Lang, a cardiologist at the University of Dundee. “I think there's always cause for concern about that kind of analysis,” he added.

Dr. Lang reported on more than 9,000 Tayside residents with type 2 diabetes, 841 of whom developed heart failure during the period from 1991 to 2008. Each diabetic heart failure patient was matched by age, gender, and date of diagnosis of diabetes to five controls.

When Dr. Lang and his coinvestigators conducted a multivariate logistic regression analysis, they found that the mean HbA1c _level during the study period was associated in linear fashion with the risk of later developing heart failure.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure after the researchers controlled for patients' mean arterial pressure and use of thiazoli-dinediones.

Further, in type 2 diabetic patients who were diagnosed with heart failure, each 1% increase in mean HbA1_c was independently associated with an adjusted 16% increase in all-cause mortality, according to Dr. Lang.

“I think our findings are an argument for tight glycemic control in diabetic patients with heart failure. The question is how to achieve that. I'm a big believer in metformin for that purpose,” the cardiologist said.

When Dr. Lang was asked whether the increased risk of mortality documented in diabetic patients with poor glycemic control and heart failure is a marker for poor adherence to standard heart failure medications or is due to the adverse effects of high blood glucose, he said that's a key unsettled question.

“We have the ability to look at treatment adherence in this cohort and are doing so at the moment,” Dr. Lang noted.

He declared that he had no financial conflicts in connection with the study, which was conducted free of industry involvement.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure.

Source DR. LANG

STOCKHOLM – Suboptimal glycemic control is an independent risk factor for a linear increase in the rate of new-onset heart failure in patients with type 2 diabetes, a large Scottish prospective case-control study indicates.

Moreover, in type 2 diabetes patients who already have established heart failure, poor glycemic control is independently associated with increased mortality, Dr. Chim Choy Lang reported at the congress.

These were the key findings in a new analysis from the Tayside Study, which is directed by Dr. Lang. The ongoing project provides an unusual opportunity to prospectively follow an entire Scottish community, population 400,000.

“We can track patients with diabetes mellitus, looking at mean [hemoglobin A_1c] over time, and see who develops heart failure,” Dr. Lang said in an interview.

“Our bioinformatics platform allows us to track all sorts of biologic variables, prescribing information, and outcomes data,” he explained.

The analysis of Tayside Study data was performed because controversy has arisen surrounding the relationship between glycemic control in type 2 diabetes and heart failure.

Some recent evidence has suggested that tight metabolic control in type 2 diabetes is actually associated with worse survival of patients in the setting of heart failure.

“It should be noted that most of these studies were based on a single measure of HbA_1c,” observed Dr. Lang, a cardiologist at the University of Dundee. “I think there's always cause for concern about that kind of analysis,” he added.

Dr. Lang reported on more than 9,000 Tayside residents with type 2 diabetes, 841 of whom developed heart failure during the period from 1991 to 2008. Each diabetic heart failure patient was matched by age, gender, and date of diagnosis of diabetes to five controls.

When Dr. Lang and his coinvestigators conducted a multivariate logistic regression analysis, they found that the mean HbA1c _level during the study period was associated in linear fashion with the risk of later developing heart failure.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure after the researchers controlled for patients' mean arterial pressure and use of thiazoli-dinediones.

Further, in type 2 diabetic patients who were diagnosed with heart failure, each 1% increase in mean HbA1_c was independently associated with an adjusted 16% increase in all-cause mortality, according to Dr. Lang.

“I think our findings are an argument for tight glycemic control in diabetic patients with heart failure. The question is how to achieve that. I'm a big believer in metformin for that purpose,” the cardiologist said.

When Dr. Lang was asked whether the increased risk of mortality documented in diabetic patients with poor glycemic control and heart failure is a marker for poor adherence to standard heart failure medications or is due to the adverse effects of high blood glucose, he said that's a key unsettled question.

“We have the ability to look at treatment adherence in this cohort and are doing so at the moment,” Dr. Lang noted.

He declared that he had no financial conflicts in connection with the study, which was conducted free of industry involvement.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure.

Source DR. LANG

STOCKHOLM – Suboptimal glycemic control is an independent risk factor for a linear increase in the rate of new-onset heart failure in patients with type 2 diabetes, a large Scottish prospective case-control study indicates.

Moreover, in type 2 diabetes patients who already have established heart failure, poor glycemic control is independently associated with increased mortality, Dr. Chim Choy Lang reported at the congress.

These were the key findings in a new analysis from the Tayside Study, which is directed by Dr. Lang. The ongoing project provides an unusual opportunity to prospectively follow an entire Scottish community, population 400,000.

“We can track patients with diabetes mellitus, looking at mean [hemoglobin A_1c] over time, and see who develops heart failure,” Dr. Lang said in an interview.

“Our bioinformatics platform allows us to track all sorts of biologic variables, prescribing information, and outcomes data,” he explained.

The analysis of Tayside Study data was performed because controversy has arisen surrounding the relationship between glycemic control in type 2 diabetes and heart failure.

Some recent evidence has suggested that tight metabolic control in type 2 diabetes is actually associated with worse survival of patients in the setting of heart failure.

“It should be noted that most of these studies were based on a single measure of HbA_1c,” observed Dr. Lang, a cardiologist at the University of Dundee. “I think there's always cause for concern about that kind of analysis,” he added.

Dr. Lang reported on more than 9,000 Tayside residents with type 2 diabetes, 841 of whom developed heart failure during the period from 1991 to 2008. Each diabetic heart failure patient was matched by age, gender, and date of diagnosis of diabetes to five controls.

When Dr. Lang and his coinvestigators conducted a multivariate logistic regression analysis, they found that the mean HbA1c _level during the study period was associated in linear fashion with the risk of later developing heart failure.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure after the researchers controlled for patients' mean arterial pressure and use of thiazoli-dinediones.

Further, in type 2 diabetic patients who were diagnosed with heart failure, each 1% increase in mean HbA1_c was independently associated with an adjusted 16% increase in all-cause mortality, according to Dr. Lang.

“I think our findings are an argument for tight glycemic control in diabetic patients with heart failure. The question is how to achieve that. I'm a big believer in metformin for that purpose,” the cardiologist said.

When Dr. Lang was asked whether the increased risk of mortality documented in diabetic patients with poor glycemic control and heart failure is a marker for poor adherence to standard heart failure medications or is due to the adverse effects of high blood glucose, he said that's a key unsettled question.

“We have the ability to look at treatment adherence in this cohort and are doing so at the moment,” Dr. Lang noted.

He declared that he had no financial conflicts in connection with the study, which was conducted free of industry involvement.

Each 1% increase in HbA_1c was independently linked to a 19% increase in incident heart failure.

Source DR. LANG

SAN DIEGO – Plasma levels of serotonin were significantly elevated in patients with decompensated systolic heart failure, compared with patients in the compensated state and with normal controls, according to a single-center study.

The finding suggests that serotonin has an active role in the progression of heart failure (HF), researchers led by Dr. Ahmed M. Selim reported during a poster session at the meeting.

“More studies should be done to test the sensitivity, specificity, and prognostic value of serotonin as a marker for congestive heart failure,” wrote the researchers from the department of cardiology at Albert Einstein College of Medicine, New York.

They noted that, while the relationship between HF and the serotoninergic system has been established in previous research, fluctuations in serotonin levels during the course of the disease and its correlation with exacerbation of HF have never been tested.

Dr. Selim and his associates measured plasma serotonin levels in 29 patients admitted with decompensated HF, 61 with stable HF, and 22 normal controls.

Overall, the mean age of patients was 55 years, and 62% were male.

The researchers reported that the mean serotonin level in the control group was 2.4 ng/mL, vs. 4.1 ng/mL in the compensated group and 11.8 ng/mL in the decompensated group. “All results were highly significant,” the researchers wrote.

Dr. Selim and his associates stated that they had no relevant financial conflicts of interest.

SAN DIEGO – Plasma levels of serotonin were significantly elevated in patients with decompensated systolic heart failure, compared with patients in the compensated state and with normal controls, according to a single-center study.

The finding suggests that serotonin has an active role in the progression of heart failure (HF), researchers led by Dr. Ahmed M. Selim reported during a poster session at the meeting.

“More studies should be done to test the sensitivity, specificity, and prognostic value of serotonin as a marker for congestive heart failure,” wrote the researchers from the department of cardiology at Albert Einstein College of Medicine, New York.

They noted that, while the relationship between HF and the serotoninergic system has been established in previous research, fluctuations in serotonin levels during the course of the disease and its correlation with exacerbation of HF have never been tested.

Dr. Selim and his associates measured plasma serotonin levels in 29 patients admitted with decompensated HF, 61 with stable HF, and 22 normal controls.

Overall, the mean age of patients was 55 years, and 62% were male.

The researchers reported that the mean serotonin level in the control group was 2.4 ng/mL, vs. 4.1 ng/mL in the compensated group and 11.8 ng/mL in the decompensated group. “All results were highly significant,” the researchers wrote.

Dr. Selim and his associates stated that they had no relevant financial conflicts of interest.

SAN DIEGO – Plasma levels of serotonin were significantly elevated in patients with decompensated systolic heart failure, compared with patients in the compensated state and with normal controls, according to a single-center study.

The finding suggests that serotonin has an active role in the progression of heart failure (HF), researchers led by Dr. Ahmed M. Selim reported during a poster session at the meeting.

“More studies should be done to test the sensitivity, specificity, and prognostic value of serotonin as a marker for congestive heart failure,” wrote the researchers from the department of cardiology at Albert Einstein College of Medicine, New York.

They noted that, while the relationship between HF and the serotoninergic system has been established in previous research, fluctuations in serotonin levels during the course of the disease and its correlation with exacerbation of HF have never been tested.

Dr. Selim and his associates measured plasma serotonin levels in 29 patients admitted with decompensated HF, 61 with stable HF, and 22 normal controls.

Overall, the mean age of patients was 55 years, and 62% were male.

The researchers reported that the mean serotonin level in the control group was 2.4 ng/mL, vs. 4.1 ng/mL in the compensated group and 11.8 ng/mL in the decompensated group. “All results were highly significant,” the researchers wrote.

Dr. Selim and his associates stated that they had no relevant financial conflicts of interest.

Major Finding: Patients with NYHA stage III or IV heart failure who received gene therapy with MYDICAR had cardiovascular-related hospital stays that averaged 2 fewer days than those who received placebo.

Data Source: A phase II study of 39 patients enrolled in the CUPID trial.

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

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

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

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A viral vectoridelivers the SERCA2a gene.

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

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

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

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

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

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group. In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but theidifferencedias not significantce.

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

Improvements were seen in the treatment group, vs. placebo, in 6-minute walk tests and end systolic volume.

Source DR. GREENBERG

Major Finding: Patients with NYHA stage III or IV heart failure who received gene therapy with MYDICAR had cardiovascular-related hospital stays that averaged 2 fewer days than those who received placebo.

Data Source: A phase II study of 39 patients enrolled in the CUPID trial.

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

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

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

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A viral vectoridelivers the SERCA2a gene.

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

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

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

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

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

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group. In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but theidifferencedias not significantce.

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

Improvements were seen in the treatment group, vs. placebo, in 6-minute walk tests and end systolic volume.

Source DR. GREENBERG

Major Finding: Patients with NYHA stage III or IV heart failure who received gene therapy with MYDICAR had cardiovascular-related hospital stays that averaged 2 fewer days than those who received placebo.

Data Source: A phase II study of 39 patients enrolled in the CUPID trial.

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

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

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

MYDICAR, manufactured by Celladon Corp., is an enzyme replacement therapy that is designed to restore levels of SERCA2a. A viral vectoridelivers the SERCA2a gene.

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

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

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

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

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

In the individual analysis, the mean efficacy “score” for the treatment was significantly greater than that of the placebo group. In the time-to-death analysis, the treatment group scored numerically better than the placebo group, but theidifferencedias not significantce.

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

Improvements were seen in the treatment group, vs. placebo, in 6-minute walk tests and end systolic volume.

Source DR. GREENBERG

STOCKHOLM – The absence of signs and symptoms of congestion at discharge in patients hospitalized for acute decompensated heart failure does not predict a favorable prognosis, contrary to the conventional wisdom.

A new secondary analysis of the international EVEREST trial provides an important lesson in the everyday management of acute heart failure: “The fact that a patient improves in-hospital with diuretics and other medications is not sufficient. It's not 'mission accomplished,'” Dr. Mihai Gheorghiade said at the congress.

“There is a dissociation between signs and symptoms of congestion at discharge and outcomes. In spite of having a very low congestion score, the event rate in EVEREST during 10 months of follow-up was astronomical,” said Dr. Gheorghiade, professor of medicine and surgery and associate chief of cardiology at Northwestern University, Chicago.

EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) was a double-blind study that randomized 4,133 patients with worsening heart failure and a left ventricular ejection fraction of 40% or less to the oral vasopressin V2 receptor blocker tolvaptan or placebo within 48 hours of hospitalization.

Standard background therapy in both study arms included diuretics, ACE inhibitor or angiotensin II receptor blocker therapy, a beta-blocker, and an aldosterone antagonist. In the previously reported primary results, tolvaptan proved to have no benefit over placebo during a mean follow-up of 9.9 months (JAMA 2007;297:1319–31).

Dr. Gheorghiade presented a secondary analysis focusing on the 2,061 patients in the placebo arm. At randomization, following initial treatment with diuretics, these patients had a mean congestion score of 4 points based on their degree of jugular vein distention, rales, and peripheral edema.

At discharge, patients had lost a mean 2.8 kg of body weight, and 72% had a congestion score of 0 or 1. Although that appears to be a high rate of short-term treatment success, this large subgroup of patients with minimal or no signs or symptoms of congestion at discharge had a 15% all-cause mortality and a 29% rate of rehospitalization for heart failure during the next 9.9 months.

The adverse event rate was even greater in those with a higher congestion score at discharge. In the overall placebo group, all-cause mortality was 26%, with a 40% rate of rehospitalization for heart failure during follow-up.

“We're dealing with a disorder that has an event rate as high as 50%. There is no other medical condition for which patients are hospitalized and are improving with therapy that has a comparable event rate,” the cardiologist observed.

The new EVEREST analysis contains an important message for clinical trialists: Using signs and symptoms of congestion as a key target for treatment during hospitalization as well as the standard end point in acute heart failure studies, as has been common until now, is a recipe for a negative trial result.

“It's very difficult to beat placebo, because placebo plus standard therapy has a tremendous effect on congestion,” Dr. Gheorghiade said. “Looking for new therapies that improve signs and symptoms of congestion in the whole population is a waste of time unless you're dealing with special populations who don't respond to standard therapies, such as patients with low blood pressure.”

Better surrogate markers than congestion are needed to guide therapy. One possibility is B-type natriuretic peptide (BNP). The mean BNP at admission in the placebo arm of EVEREST was 1,375 pg/mL. At discharge it was still markedly elevated at 948 pg/mL.

“The lesson here is that by treating the signs and symptoms of congestion, you can make patients feel much better, but even though they are now able to walk up a flight of stairs, inside, in terms of renal function and BNP, they are still very sick,” he said.

Until better treatments for acute heart failure are found, the best thing physicians can do for patients is try to identify specific targets amenable to current therapies, such as renal dysfunction or myocardial ischemia, Dr. Gheorghiade said.

The EVEREST trial was sponsored by Otsuka. Dr. Gheorghiade has received research grants and/or served as a consultant to Otsuka and numerous other pharmaceutical companies.

Dr. Mihai Gheorghiade: The event rate in EVEREST was “astronomical.”

Source Bruce Jancin/Elsevier Global Medical News

STOCKHOLM – The absence of signs and symptoms of congestion at discharge in patients hospitalized for acute decompensated heart failure does not predict a favorable prognosis, contrary to the conventional wisdom.

A new secondary analysis of the international EVEREST trial provides an important lesson in the everyday management of acute heart failure: “The fact that a patient improves in-hospital with diuretics and other medications is not sufficient. It's not 'mission accomplished,'” Dr. Mihai Gheorghiade said at the congress.

“There is a dissociation between signs and symptoms of congestion at discharge and outcomes. In spite of having a very low congestion score, the event rate in EVEREST during 10 months of follow-up was astronomical,” said Dr. Gheorghiade, professor of medicine and surgery and associate chief of cardiology at Northwestern University, Chicago.

EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) was a double-blind study that randomized 4,133 patients with worsening heart failure and a left ventricular ejection fraction of 40% or less to the oral vasopressin V2 receptor blocker tolvaptan or placebo within 48 hours of hospitalization.

Standard background therapy in both study arms included diuretics, ACE inhibitor or angiotensin II receptor blocker therapy, a beta-blocker, and an aldosterone antagonist. In the previously reported primary results, tolvaptan proved to have no benefit over placebo during a mean follow-up of 9.9 months (JAMA 2007;297:1319–31).

Dr. Gheorghiade presented a secondary analysis focusing on the 2,061 patients in the placebo arm. At randomization, following initial treatment with diuretics, these patients had a mean congestion score of 4 points based on their degree of jugular vein distention, rales, and peripheral edema.

At discharge, patients had lost a mean 2.8 kg of body weight, and 72% had a congestion score of 0 or 1. Although that appears to be a high rate of short-term treatment success, this large subgroup of patients with minimal or no signs or symptoms of congestion at discharge had a 15% all-cause mortality and a 29% rate of rehospitalization for heart failure during the next 9.9 months.

The adverse event rate was even greater in those with a higher congestion score at discharge. In the overall placebo group, all-cause mortality was 26%, with a 40% rate of rehospitalization for heart failure during follow-up.

“We're dealing with a disorder that has an event rate as high as 50%. There is no other medical condition for which patients are hospitalized and are improving with therapy that has a comparable event rate,” the cardiologist observed.

The new EVEREST analysis contains an important message for clinical trialists: Using signs and symptoms of congestion as a key target for treatment during hospitalization as well as the standard end point in acute heart failure studies, as has been common until now, is a recipe for a negative trial result.

“It's very difficult to beat placebo, because placebo plus standard therapy has a tremendous effect on congestion,” Dr. Gheorghiade said. “Looking for new therapies that improve signs and symptoms of congestion in the whole population is a waste of time unless you're dealing with special populations who don't respond to standard therapies, such as patients with low blood pressure.”

Better surrogate markers than congestion are needed to guide therapy. One possibility is B-type natriuretic peptide (BNP). The mean BNP at admission in the placebo arm of EVEREST was 1,375 pg/mL. At discharge it was still markedly elevated at 948 pg/mL.

“The lesson here is that by treating the signs and symptoms of congestion, you can make patients feel much better, but even though they are now able to walk up a flight of stairs, inside, in terms of renal function and BNP, they are still very sick,” he said.

Until better treatments for acute heart failure are found, the best thing physicians can do for patients is try to identify specific targets amenable to current therapies, such as renal dysfunction or myocardial ischemia, Dr. Gheorghiade said.

The EVEREST trial was sponsored by Otsuka. Dr. Gheorghiade has received research grants and/or served as a consultant to Otsuka and numerous other pharmaceutical companies.

Dr. Mihai Gheorghiade: The event rate in EVEREST was “astronomical.”

Source Bruce Jancin/Elsevier Global Medical News

STOCKHOLM – The absence of signs and symptoms of congestion at discharge in patients hospitalized for acute decompensated heart failure does not predict a favorable prognosis, contrary to the conventional wisdom.

A new secondary analysis of the international EVEREST trial provides an important lesson in the everyday management of acute heart failure: “The fact that a patient improves in-hospital with diuretics and other medications is not sufficient. It's not 'mission accomplished,'” Dr. Mihai Gheorghiade said at the congress.

“There is a dissociation between signs and symptoms of congestion at discharge and outcomes. In spite of having a very low congestion score, the event rate in EVEREST during 10 months of follow-up was astronomical,” said Dr. Gheorghiade, professor of medicine and surgery and associate chief of cardiology at Northwestern University, Chicago.

EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan) was a double-blind study that randomized 4,133 patients with worsening heart failure and a left ventricular ejection fraction of 40% or less to the oral vasopressin V2 receptor blocker tolvaptan or placebo within 48 hours of hospitalization.

Standard background therapy in both study arms included diuretics, ACE inhibitor or angiotensin II receptor blocker therapy, a beta-blocker, and an aldosterone antagonist. In the previously reported primary results, tolvaptan proved to have no benefit over placebo during a mean follow-up of 9.9 months (JAMA 2007;297:1319–31).

Dr. Gheorghiade presented a secondary analysis focusing on the 2,061 patients in the placebo arm. At randomization, following initial treatment with diuretics, these patients had a mean congestion score of 4 points based on their degree of jugular vein distention, rales, and peripheral edema.

At discharge, patients had lost a mean 2.8 kg of body weight, and 72% had a congestion score of 0 or 1. Although that appears to be a high rate of short-term treatment success, this large subgroup of patients with minimal or no signs or symptoms of congestion at discharge had a 15% all-cause mortality and a 29% rate of rehospitalization for heart failure during the next 9.9 months.

The adverse event rate was even greater in those with a higher congestion score at discharge. In the overall placebo group, all-cause mortality was 26%, with a 40% rate of rehospitalization for heart failure during follow-up.

“We're dealing with a disorder that has an event rate as high as 50%. There is no other medical condition for which patients are hospitalized and are improving with therapy that has a comparable event rate,” the cardiologist observed.

The new EVEREST analysis contains an important message for clinical trialists: Using signs and symptoms of congestion as a key target for treatment during hospitalization as well as the standard end point in acute heart failure studies, as has been common until now, is a recipe for a negative trial result.

“It's very difficult to beat placebo, because placebo plus standard therapy has a tremendous effect on congestion,” Dr. Gheorghiade said. “Looking for new therapies that improve signs and symptoms of congestion in the whole population is a waste of time unless you're dealing with special populations who don't respond to standard therapies, such as patients with low blood pressure.”

Better surrogate markers than congestion are needed to guide therapy. One possibility is B-type natriuretic peptide (BNP). The mean BNP at admission in the placebo arm of EVEREST was 1,375 pg/mL. At discharge it was still markedly elevated at 948 pg/mL.

“The lesson here is that by treating the signs and symptoms of congestion, you can make patients feel much better, but even though they are now able to walk up a flight of stairs, inside, in terms of renal function and BNP, they are still very sick,” he said.

Until better treatments for acute heart failure are found, the best thing physicians can do for patients is try to identify specific targets amenable to current therapies, such as renal dysfunction or myocardial ischemia, Dr. Gheorghiade said.

The EVEREST trial was sponsored by Otsuka. Dr. Gheorghiade has received research grants and/or served as a consultant to Otsuka and numerous other pharmaceutical companies.

Dr. Mihai Gheorghiade: The event rate in EVEREST was “astronomical.”

Source Bruce Jancin/Elsevier Global Medical News

Major Finding: Adults with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal levels of vitamin D. They were also 1.45 times as likely to die prematurely, compared with those who had normal levels of vitamin D.

Data Source: A total of 13,131 men and women aged 35 and older enrolled in the prospective cohort of the NHANES III from 1988 to 1994.

Disclosures: The researchers had no relevant financial disclosures to make.

SAN DIEGO — Adults with decreased levels of serum 25-hydroxyvitamin D are significantly more likely to die from heart failure or die prematurely, compared with adults who have normal serum levels of vitamin D, results from a large analysis found.

“This may be additional justification for a study of vitamin D supplementation in appropriate patients to determine if there is causality and if this is a treatable condition,” Dr. Howard J. Eisen said at the meeting.

In a study led by his associate, Dr. Longjian Liu of the department of epidemiology and biostatistics at Drexel University School of Public Health, Philadelphia, the researchers reviewed data from 13,131 individuals (6,130 men and 7,001 women) aged 35 and older who were enrolled in the prospective cohort of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988 to 1994 and followed for mortality through the year 2000. At baseline, a radioimmunoassay kit was used to measure the serum vitamin D level of each participant.

Vitamin D deficiency was defined as a serum level below 20 ng/mL, and vitamin D insufficiency was defined as a serum level of 20-29 ng/mL. Normal levels were defined as 30 ng/mL or greater, said Dr. Eisen of the department of medicine at Drexel University, Philadelphia.

Premature death was defined as death before the age of 75. The researchers used Cox proportional hazards regression analysis to examine the association between serum levels of vitamin D and mortality risk.

Dr. Eisen reported that more than 60% of African American study participants were vitamin D deficient, compared with 20% of whites and about 40% of Hispanics. “This might be yet another explanation for the high prevalence of heart failure [among African Americans],” he said.

During an average follow-up period of 8 years, there were 3,266 deaths among the 13,131 participants (24.9%), including 101 heart failure deaths (0.8%). Of the total deaths, there were 1,066 premature deaths (33%). Death from cardiovascular disease accounted for as many as 34% of the total premature deaths.

The rate of vitamin D deficiency among heart failure deaths was 37%, compared with 26% among non–heart failure–related deaths, a difference that was statistically significant.

After the researchers adjusted for age, gender, race, and baseline medical conditions, study participants with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 2 times more likely to die from heart failure, compared with those who had normal vitamin D levels.

In addition, study participants with vitamin D deficiency were 1.45 times more likely to die prematurely, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 1.14 times more likely to die prematurely, compared with those who had normal vitamin D levels.

Major Finding: Adults with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal levels of vitamin D. They were also 1.45 times as likely to die prematurely, compared with those who had normal levels of vitamin D.

Data Source: A total of 13,131 men and women aged 35 and older enrolled in the prospective cohort of the NHANES III from 1988 to 1994.

Disclosures: The researchers had no relevant financial disclosures to make.

SAN DIEGO — Adults with decreased levels of serum 25-hydroxyvitamin D are significantly more likely to die from heart failure or die prematurely, compared with adults who have normal serum levels of vitamin D, results from a large analysis found.

“This may be additional justification for a study of vitamin D supplementation in appropriate patients to determine if there is causality and if this is a treatable condition,” Dr. Howard J. Eisen said at the meeting.

In a study led by his associate, Dr. Longjian Liu of the department of epidemiology and biostatistics at Drexel University School of Public Health, Philadelphia, the researchers reviewed data from 13,131 individuals (6,130 men and 7,001 women) aged 35 and older who were enrolled in the prospective cohort of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988 to 1994 and followed for mortality through the year 2000. At baseline, a radioimmunoassay kit was used to measure the serum vitamin D level of each participant.

Vitamin D deficiency was defined as a serum level below 20 ng/mL, and vitamin D insufficiency was defined as a serum level of 20-29 ng/mL. Normal levels were defined as 30 ng/mL or greater, said Dr. Eisen of the department of medicine at Drexel University, Philadelphia.

Premature death was defined as death before the age of 75. The researchers used Cox proportional hazards regression analysis to examine the association between serum levels of vitamin D and mortality risk.

Dr. Eisen reported that more than 60% of African American study participants were vitamin D deficient, compared with 20% of whites and about 40% of Hispanics. “This might be yet another explanation for the high prevalence of heart failure [among African Americans],” he said.

During an average follow-up period of 8 years, there were 3,266 deaths among the 13,131 participants (24.9%), including 101 heart failure deaths (0.8%). Of the total deaths, there were 1,066 premature deaths (33%). Death from cardiovascular disease accounted for as many as 34% of the total premature deaths.

The rate of vitamin D deficiency among heart failure deaths was 37%, compared with 26% among non–heart failure–related deaths, a difference that was statistically significant.

After the researchers adjusted for age, gender, race, and baseline medical conditions, study participants with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 2 times more likely to die from heart failure, compared with those who had normal vitamin D levels.

In addition, study participants with vitamin D deficiency were 1.45 times more likely to die prematurely, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 1.14 times more likely to die prematurely, compared with those who had normal vitamin D levels.

Major Finding: Adults with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal levels of vitamin D. They were also 1.45 times as likely to die prematurely, compared with those who had normal levels of vitamin D.

Data Source: A total of 13,131 men and women aged 35 and older enrolled in the prospective cohort of the NHANES III from 1988 to 1994.

Disclosures: The researchers had no relevant financial disclosures to make.

SAN DIEGO — Adults with decreased levels of serum 25-hydroxyvitamin D are significantly more likely to die from heart failure or die prematurely, compared with adults who have normal serum levels of vitamin D, results from a large analysis found.

“This may be additional justification for a study of vitamin D supplementation in appropriate patients to determine if there is causality and if this is a treatable condition,” Dr. Howard J. Eisen said at the meeting.

In a study led by his associate, Dr. Longjian Liu of the department of epidemiology and biostatistics at Drexel University School of Public Health, Philadelphia, the researchers reviewed data from 13,131 individuals (6,130 men and 7,001 women) aged 35 and older who were enrolled in the prospective cohort of the Third National Health and Nutrition Examination Survey (NHANES III) from 1988 to 1994 and followed for mortality through the year 2000. At baseline, a radioimmunoassay kit was used to measure the serum vitamin D level of each participant.

Vitamin D deficiency was defined as a serum level below 20 ng/mL, and vitamin D insufficiency was defined as a serum level of 20-29 ng/mL. Normal levels were defined as 30 ng/mL or greater, said Dr. Eisen of the department of medicine at Drexel University, Philadelphia.

Premature death was defined as death before the age of 75. The researchers used Cox proportional hazards regression analysis to examine the association between serum levels of vitamin D and mortality risk.

Dr. Eisen reported that more than 60% of African American study participants were vitamin D deficient, compared with 20% of whites and about 40% of Hispanics. “This might be yet another explanation for the high prevalence of heart failure [among African Americans],” he said.

During an average follow-up period of 8 years, there were 3,266 deaths among the 13,131 participants (24.9%), including 101 heart failure deaths (0.8%). Of the total deaths, there were 1,066 premature deaths (33%). Death from cardiovascular disease accounted for as many as 34% of the total premature deaths.

The rate of vitamin D deficiency among heart failure deaths was 37%, compared with 26% among non–heart failure–related deaths, a difference that was statistically significant.

After the researchers adjusted for age, gender, race, and baseline medical conditions, study participants with vitamin D deficiency were 3.4 times more likely to die from heart failure, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 2 times more likely to die from heart failure, compared with those who had normal vitamin D levels.

In addition, study participants with vitamin D deficiency were 1.45 times more likely to die prematurely, compared with those who had normal vitamin D levels, while those with vitamin D insufficiency were 1.14 times more likely to die prematurely, compared with those who had normal vitamin D levels.