Heart Failure

ATLANTA — Predischarge initiation of β-blocker therapy in patients with heart failure and left ventricular systolic dysfunction halved mortality during the next 60–90 days among 5,791 patients in a registry, Dr. Gregg C. Fonarow reported at the annual meeting of the American College of Cardiology.

Inpatient initiation of β-blocker therapy ought to be considered a standard of care in heart failure management, according to Dr. Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

The treatment has all the elements of an ideal clinical performance measure for use in quality improvement and pay-for-performance programs.

And yet it was not included among the five inpatient performance measures for adults with chronic heart failure that were recently published by an ACC/American Heart Association (AHA) task force. That is an oversight, and the issue deserves to be revisited, Dr. Fonarow said.

He reported on 5,791 heart failure patients in 91 U.S. hospitals who comprised a prespecified subgroup with prospective follow-up among enrollees in the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry.

Of the 53% who had left ventricular systolic dysfunction, 90% were deemed eligible for β-blocker therapy at discharge. And of those eligible, 84% were actually discharged on a β-blocker, and 93% of those remained on the drug at 60- to 90-day follow-up.

Postdischarge 60- to 90-day all-cause mortality in patients eligible for β-blocker therapy who weren't discharged on it was 11.1%, with a combined rate of death or rehospitalization of 42%.

A risk-adjusted multivariate analysis showed that discharge on a β-blocker was associated with a highly significant 49% reduction in all-cause mortality and a 28% reduction in death or rehospitalization, compared with rates in the eligible-but-untreated group.

Dr. Fonarow stressed that when he and his coinvestigators applied the five recently published ACC/AHA performance measures to the OPTIMIZE-HF cohort of nearly 6,000 patients, none of the five predicted 60- to 90-day mortality, and only one—discharge on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ARB)—was associated with a significant reduction in the combined death or rehospitalization end point.

In addition to discharge on an ACE inhibitor or ARB, the other current ACC/AHA inpatient performance indicators are the evaluation of left ventricular systolic function, the issuance of discharge instructions, smoking cessation advice/counseling, and discharge anticoagulation for heart failure patients with atrial fibrillation.

The ACC/AHA task force considered including β-blockade as an inpatient performance measure but elected not to on the grounds that “the complexities of establishing the right conditions under which stable HF patients would be included in the measure minus the exclusions would result in so small a denominator that the measure would not be meaningful at this time” (J. Am. Coll. Cardiol. 2005;46:1144–78). But this was an assumption not based on data—and the OPTIMIZE-HF experience undercuts the task force's rationale, Dr. Fonarow said in an interview.

“Here in OPTIMIZE-HF are the actual prospective data showing that a large number of patients qualify for β-blocker therapy, the tolerability is phenomenal, and it's the most important measure with respect to outcome prediction in terms of death and rehospitalization.

“So if you were to ask in terms of actual data what would be the most important performance measure for heart failure at the time of discharge, it would be β-blocker therapy, followed by ACE inhibitor/ARBs,” he said.

Although the other current performance measures may be important in terms of long-term care, the finding that they do not improve 60- to 90-day mortality or rehospitalization means they do not address the highest priority issues, Dr. Fonarow continued.

Task force member Dr. Kim A. Eagle, the clinical director of the University of Michigan Cardiovascular Center, Ann Arbor, said in an interview that it is unclear whether the group will reconsider adding inpatient β-blocker therapy as a heart failure performance indicator.

There is a concern that starting the therapy too early—before a patient is stabilized—can have adverse consequences, he added.

The OPTIMIZE-HF registry is funded by GlaxoSmithKline. Last year, the registry was incorporated into AHA's ongoing Get With The Guidelines-Heart Failure project.

ATLANTA — Predischarge initiation of β-blocker therapy in patients with heart failure and left ventricular systolic dysfunction halved mortality during the next 60–90 days among 5,791 patients in a registry, Dr. Gregg C. Fonarow reported at the annual meeting of the American College of Cardiology.

Inpatient initiation of β-blocker therapy ought to be considered a standard of care in heart failure management, according to Dr. Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

The treatment has all the elements of an ideal clinical performance measure for use in quality improvement and pay-for-performance programs.

And yet it was not included among the five inpatient performance measures for adults with chronic heart failure that were recently published by an ACC/American Heart Association (AHA) task force. That is an oversight, and the issue deserves to be revisited, Dr. Fonarow said.

He reported on 5,791 heart failure patients in 91 U.S. hospitals who comprised a prespecified subgroup with prospective follow-up among enrollees in the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry.

Of the 53% who had left ventricular systolic dysfunction, 90% were deemed eligible for β-blocker therapy at discharge. And of those eligible, 84% were actually discharged on a β-blocker, and 93% of those remained on the drug at 60- to 90-day follow-up.

Postdischarge 60- to 90-day all-cause mortality in patients eligible for β-blocker therapy who weren't discharged on it was 11.1%, with a combined rate of death or rehospitalization of 42%.

A risk-adjusted multivariate analysis showed that discharge on a β-blocker was associated with a highly significant 49% reduction in all-cause mortality and a 28% reduction in death or rehospitalization, compared with rates in the eligible-but-untreated group.

Dr. Fonarow stressed that when he and his coinvestigators applied the five recently published ACC/AHA performance measures to the OPTIMIZE-HF cohort of nearly 6,000 patients, none of the five predicted 60- to 90-day mortality, and only one—discharge on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ARB)—was associated with a significant reduction in the combined death or rehospitalization end point.

In addition to discharge on an ACE inhibitor or ARB, the other current ACC/AHA inpatient performance indicators are the evaluation of left ventricular systolic function, the issuance of discharge instructions, smoking cessation advice/counseling, and discharge anticoagulation for heart failure patients with atrial fibrillation.

The ACC/AHA task force considered including β-blockade as an inpatient performance measure but elected not to on the grounds that “the complexities of establishing the right conditions under which stable HF patients would be included in the measure minus the exclusions would result in so small a denominator that the measure would not be meaningful at this time” (J. Am. Coll. Cardiol. 2005;46:1144–78). But this was an assumption not based on data—and the OPTIMIZE-HF experience undercuts the task force's rationale, Dr. Fonarow said in an interview.

“Here in OPTIMIZE-HF are the actual prospective data showing that a large number of patients qualify for β-blocker therapy, the tolerability is phenomenal, and it's the most important measure with respect to outcome prediction in terms of death and rehospitalization.

“So if you were to ask in terms of actual data what would be the most important performance measure for heart failure at the time of discharge, it would be β-blocker therapy, followed by ACE inhibitor/ARBs,” he said.

Although the other current performance measures may be important in terms of long-term care, the finding that they do not improve 60- to 90-day mortality or rehospitalization means they do not address the highest priority issues, Dr. Fonarow continued.

Task force member Dr. Kim A. Eagle, the clinical director of the University of Michigan Cardiovascular Center, Ann Arbor, said in an interview that it is unclear whether the group will reconsider adding inpatient β-blocker therapy as a heart failure performance indicator.

There is a concern that starting the therapy too early—before a patient is stabilized—can have adverse consequences, he added.

The OPTIMIZE-HF registry is funded by GlaxoSmithKline. Last year, the registry was incorporated into AHA's ongoing Get With The Guidelines-Heart Failure project.

ATLANTA — Predischarge initiation of β-blocker therapy in patients with heart failure and left ventricular systolic dysfunction halved mortality during the next 60–90 days among 5,791 patients in a registry, Dr. Gregg C. Fonarow reported at the annual meeting of the American College of Cardiology.

Inpatient initiation of β-blocker therapy ought to be considered a standard of care in heart failure management, according to Dr. Fonarow, professor of medicine at the University of California, Los Angeles, and director of the Ahmanson-UCLA Cardiomyopathy Center.

The treatment has all the elements of an ideal clinical performance measure for use in quality improvement and pay-for-performance programs.

And yet it was not included among the five inpatient performance measures for adults with chronic heart failure that were recently published by an ACC/American Heart Association (AHA) task force. That is an oversight, and the issue deserves to be revisited, Dr. Fonarow said.

He reported on 5,791 heart failure patients in 91 U.S. hospitals who comprised a prespecified subgroup with prospective follow-up among enrollees in the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry.

Of the 53% who had left ventricular systolic dysfunction, 90% were deemed eligible for β-blocker therapy at discharge. And of those eligible, 84% were actually discharged on a β-blocker, and 93% of those remained on the drug at 60- to 90-day follow-up.

Postdischarge 60- to 90-day all-cause mortality in patients eligible for β-blocker therapy who weren't discharged on it was 11.1%, with a combined rate of death or rehospitalization of 42%.

A risk-adjusted multivariate analysis showed that discharge on a β-blocker was associated with a highly significant 49% reduction in all-cause mortality and a 28% reduction in death or rehospitalization, compared with rates in the eligible-but-untreated group.

Dr. Fonarow stressed that when he and his coinvestigators applied the five recently published ACC/AHA performance measures to the OPTIMIZE-HF cohort of nearly 6,000 patients, none of the five predicted 60- to 90-day mortality, and only one—discharge on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ARB)—was associated with a significant reduction in the combined death or rehospitalization end point.

In addition to discharge on an ACE inhibitor or ARB, the other current ACC/AHA inpatient performance indicators are the evaluation of left ventricular systolic function, the issuance of discharge instructions, smoking cessation advice/counseling, and discharge anticoagulation for heart failure patients with atrial fibrillation.

The ACC/AHA task force considered including β-blockade as an inpatient performance measure but elected not to on the grounds that “the complexities of establishing the right conditions under which stable HF patients would be included in the measure minus the exclusions would result in so small a denominator that the measure would not be meaningful at this time” (J. Am. Coll. Cardiol. 2005;46:1144–78). But this was an assumption not based on data—and the OPTIMIZE-HF experience undercuts the task force's rationale, Dr. Fonarow said in an interview.

“Here in OPTIMIZE-HF are the actual prospective data showing that a large number of patients qualify for β-blocker therapy, the tolerability is phenomenal, and it's the most important measure with respect to outcome prediction in terms of death and rehospitalization.

“So if you were to ask in terms of actual data what would be the most important performance measure for heart failure at the time of discharge, it would be β-blocker therapy, followed by ACE inhibitor/ARBs,” he said.

Although the other current performance measures may be important in terms of long-term care, the finding that they do not improve 60- to 90-day mortality or rehospitalization means they do not address the highest priority issues, Dr. Fonarow continued.

Task force member Dr. Kim A. Eagle, the clinical director of the University of Michigan Cardiovascular Center, Ann Arbor, said in an interview that it is unclear whether the group will reconsider adding inpatient β-blocker therapy as a heart failure performance indicator.

There is a concern that starting the therapy too early—before a patient is stabilized—can have adverse consequences, he added.

The OPTIMIZE-HF registry is funded by GlaxoSmithKline. Last year, the registry was incorporated into AHA's ongoing Get With The Guidelines-Heart Failure project.

ATLANTA — Treatment with an antidepressant drug relieved the mild to moderate depression that often occurs in patients with heart failure in a controlled study with 26 patients.

But the reduction of depression symptoms using a selective serotonin reuptake inhibitor generally did not improve quality of life measures in these patients, Dr. Mark R. Vesely and his associates reported in a poster at the annual meeting of the American College of Cardiology.

The findings suggest physicians should screen for depression in patients with heart failure, then treat when depression is diagnosed, he said in an interview. Treatment with an SSRI is safe and effective. Next would be to examine whether treating depression can produce any reductions in hospitalization rates or death in heart failure patients, said Dr. Vesely, a cardiologist at the University of Maryland in Baltimore.

Results from previous studies have shown that depression occurs in 24%–48% of patients with heart failure. Despite this high prevalence, “heart failure patients usually don't get treated” for depression, said Dr. Stephen S. Gottlieb, professor of medicine and director of the heart failure service at the University of Maryland and a coinvestigator for the study.

An SSRI is the logical, first-line agent to use to treat depression in a patient with heart failure because of its presumed safety in these patients. By contrast, treatment with a tricyclic antidepressant involves the risk of producing neurohormonal activation that might exacerbate the heart failure, Dr. Vesely said.

The study included patients with New York Heart Association class II or III heart failure who were diagnosed with mild or moderate depression by a score of 10 or more on the Beck Depression Index (BDI). The average BDI score of the patients enrolled was about 21, and they were all placed on an optimal panel of heart failure medications.

The patients were randomized to treatment with either paroxetine-CR (Paxil CR) 12.5 mg daily or placebo for 12 weeks. During follow-up, three patients dropped out of the study. After 12 weeks, the BDI score fell by an average of 12 points in the 12 patients treated with paroxetine-CR for the full study, compared with an average 0.5 point rise in 11 placebo patients, a significant difference.

Quality of life was measured with several scales: the Minnesota Living With Heart Failure emotional and physical scales, and the mental and physical scales of the Short Form-36. There were no significant improvements for most of these measures in the paroxetine-treated patients compared with the controls. The sole exception was the mental score on the Short Form-36, which rose by 9 points in the actively treated patients and by 1 point in the placebo-treated patients, a significant difference.

GlaxoSmithKline, which markets Paxil CR, supplied the drug in this study. The study and investigators received no other industry support.

ATLANTA — Treatment with an antidepressant drug relieved the mild to moderate depression that often occurs in patients with heart failure in a controlled study with 26 patients.

But the reduction of depression symptoms using a selective serotonin reuptake inhibitor generally did not improve quality of life measures in these patients, Dr. Mark R. Vesely and his associates reported in a poster at the annual meeting of the American College of Cardiology.

The findings suggest physicians should screen for depression in patients with heart failure, then treat when depression is diagnosed, he said in an interview. Treatment with an SSRI is safe and effective. Next would be to examine whether treating depression can produce any reductions in hospitalization rates or death in heart failure patients, said Dr. Vesely, a cardiologist at the University of Maryland in Baltimore.

Results from previous studies have shown that depression occurs in 24%–48% of patients with heart failure. Despite this high prevalence, “heart failure patients usually don't get treated” for depression, said Dr. Stephen S. Gottlieb, professor of medicine and director of the heart failure service at the University of Maryland and a coinvestigator for the study.

An SSRI is the logical, first-line agent to use to treat depression in a patient with heart failure because of its presumed safety in these patients. By contrast, treatment with a tricyclic antidepressant involves the risk of producing neurohormonal activation that might exacerbate the heart failure, Dr. Vesely said.

The study included patients with New York Heart Association class II or III heart failure who were diagnosed with mild or moderate depression by a score of 10 or more on the Beck Depression Index (BDI). The average BDI score of the patients enrolled was about 21, and they were all placed on an optimal panel of heart failure medications.

The patients were randomized to treatment with either paroxetine-CR (Paxil CR) 12.5 mg daily or placebo for 12 weeks. During follow-up, three patients dropped out of the study. After 12 weeks, the BDI score fell by an average of 12 points in the 12 patients treated with paroxetine-CR for the full study, compared with an average 0.5 point rise in 11 placebo patients, a significant difference.

Quality of life was measured with several scales: the Minnesota Living With Heart Failure emotional and physical scales, and the mental and physical scales of the Short Form-36. There were no significant improvements for most of these measures in the paroxetine-treated patients compared with the controls. The sole exception was the mental score on the Short Form-36, which rose by 9 points in the actively treated patients and by 1 point in the placebo-treated patients, a significant difference.

GlaxoSmithKline, which markets Paxil CR, supplied the drug in this study. The study and investigators received no other industry support.

ATLANTA — Treatment with an antidepressant drug relieved the mild to moderate depression that often occurs in patients with heart failure in a controlled study with 26 patients.

But the reduction of depression symptoms using a selective serotonin reuptake inhibitor generally did not improve quality of life measures in these patients, Dr. Mark R. Vesely and his associates reported in a poster at the annual meeting of the American College of Cardiology.

The findings suggest physicians should screen for depression in patients with heart failure, then treat when depression is diagnosed, he said in an interview. Treatment with an SSRI is safe and effective. Next would be to examine whether treating depression can produce any reductions in hospitalization rates or death in heart failure patients, said Dr. Vesely, a cardiologist at the University of Maryland in Baltimore.

Results from previous studies have shown that depression occurs in 24%–48% of patients with heart failure. Despite this high prevalence, “heart failure patients usually don't get treated” for depression, said Dr. Stephen S. Gottlieb, professor of medicine and director of the heart failure service at the University of Maryland and a coinvestigator for the study.

An SSRI is the logical, first-line agent to use to treat depression in a patient with heart failure because of its presumed safety in these patients. By contrast, treatment with a tricyclic antidepressant involves the risk of producing neurohormonal activation that might exacerbate the heart failure, Dr. Vesely said.

The study included patients with New York Heart Association class II or III heart failure who were diagnosed with mild or moderate depression by a score of 10 or more on the Beck Depression Index (BDI). The average BDI score of the patients enrolled was about 21, and they were all placed on an optimal panel of heart failure medications.

The patients were randomized to treatment with either paroxetine-CR (Paxil CR) 12.5 mg daily or placebo for 12 weeks. During follow-up, three patients dropped out of the study. After 12 weeks, the BDI score fell by an average of 12 points in the 12 patients treated with paroxetine-CR for the full study, compared with an average 0.5 point rise in 11 placebo patients, a significant difference.

Quality of life was measured with several scales: the Minnesota Living With Heart Failure emotional and physical scales, and the mental and physical scales of the Short Form-36. There were no significant improvements for most of these measures in the paroxetine-treated patients compared with the controls. The sole exception was the mental score on the Short Form-36, which rose by 9 points in the actively treated patients and by 1 point in the placebo-treated patients, a significant difference.

GlaxoSmithKline, which markets Paxil CR, supplied the drug in this study. The study and investigators received no other industry support.

ATLANTA — Candesartan therapy triples the already significant background risk of potentially serious hyperkalemia in patients with heart failure, according to a new secondary analysis of the Candesartan in Heart Failure—Assessment of Reduction in Mortality and Morbidity (CHARM) program.

Periodic monitoring of serum potassium is therefore “critical” in heart failure patients—and not just those on candesartan, Dr. Akshay Desai said at the annual meeting of the American College of Cardiology.

“The estimate from our study is that one would expect roughly 34 excess hyperkalemic events per 1,000 candesartan-treated patients over 3 years. But with careful surveillance of serum potassium, this risk can be substantially reduced. In the trial, seven excess serious events per 1,000 patients were noted over the 3-year duration of follow-up with careful monitoring by study investigators. We feel that this represents the unavoidable risk of candesartan therapy in this population of patients,” said Dr. Desai of Brigham and Women's Hospital, Boston.

To place this risk in perspective, he added, candesartan also prevented 43 cardiovascular death or hospitalization events per 1,000 patients.

The CHARM program involved 7,599 heart failure patients on standard therapy who were randomized in double-blind fashion to candesartan or placebo and followed for just over 3 years with regular monitoring of serum potassium. Candesartan resulted in a significant 16% reduction in the relative risk of the primary end point of cardiovascular death or heart failure hospitalization.

Hyperkalemia is well recognized to be a common and potentially life-threatening complication of treatment with renin-angiotensin-aldosterone system inhibitors. CHARM investigators categorized hyperkalemic events as “serious” if they posed a risk of death or hospitalization, and “concerning” if events were serious or would have become so if not detected early through the monitoring program, with subsequent dose adjustment or drug discontinuation.

The incidence of concerning hyperkalemia during the study was 1.8% in the placebo arm and 5.2% in the candesartan group. Serious hyperkalemic events occurred in 1.1% of the placebo group and 1.8% on candesartan. Of particular clinical relevance was the finding that hyperkalemic events were not confined to the period of candesartan dose titration; they occurred throughout follow-up, although the incidence was greater during titration, said Dr. Desai.

Several predictors of increased background risk of concerning hyperkalemia were identified. Age greater than 75 years, being on an ACE inhibitor or spironolactone, or a history of diabetes was associated with roughly a twofold increased risk. Baseline renal insufficiency or hyperkalemia conferred a fivefold spike in risk. Candesartan therapy was associated with a threefold increase in risk of hyperkalemia, compared with placebo—but the drug's therapeutic benefit was also consistent across all patient subgroups, including those at high baseline risk for hyperkalemia.

Dr. Gary S. Francis, director of the coronary intensive care unit at the Cleveland Clinic Foundation, called the new results “very important data that have practical implications.” He asked how often potassium should be monitored.

“I would suggest, particularly in patients at high baseline risk, be quite careful to measure serum potassium within a 2- to 3-week period after every dose titration, and again intermittently—even randomly—over the course of follow-up,” he said.

ATLANTA — Candesartan therapy triples the already significant background risk of potentially serious hyperkalemia in patients with heart failure, according to a new secondary analysis of the Candesartan in Heart Failure—Assessment of Reduction in Mortality and Morbidity (CHARM) program.

Periodic monitoring of serum potassium is therefore “critical” in heart failure patients—and not just those on candesartan, Dr. Akshay Desai said at the annual meeting of the American College of Cardiology.

“The estimate from our study is that one would expect roughly 34 excess hyperkalemic events per 1,000 candesartan-treated patients over 3 years. But with careful surveillance of serum potassium, this risk can be substantially reduced. In the trial, seven excess serious events per 1,000 patients were noted over the 3-year duration of follow-up with careful monitoring by study investigators. We feel that this represents the unavoidable risk of candesartan therapy in this population of patients,” said Dr. Desai of Brigham and Women's Hospital, Boston.

To place this risk in perspective, he added, candesartan also prevented 43 cardiovascular death or hospitalization events per 1,000 patients.

The CHARM program involved 7,599 heart failure patients on standard therapy who were randomized in double-blind fashion to candesartan or placebo and followed for just over 3 years with regular monitoring of serum potassium. Candesartan resulted in a significant 16% reduction in the relative risk of the primary end point of cardiovascular death or heart failure hospitalization.

Hyperkalemia is well recognized to be a common and potentially life-threatening complication of treatment with renin-angiotensin-aldosterone system inhibitors. CHARM investigators categorized hyperkalemic events as “serious” if they posed a risk of death or hospitalization, and “concerning” if events were serious or would have become so if not detected early through the monitoring program, with subsequent dose adjustment or drug discontinuation.

The incidence of concerning hyperkalemia during the study was 1.8% in the placebo arm and 5.2% in the candesartan group. Serious hyperkalemic events occurred in 1.1% of the placebo group and 1.8% on candesartan. Of particular clinical relevance was the finding that hyperkalemic events were not confined to the period of candesartan dose titration; they occurred throughout follow-up, although the incidence was greater during titration, said Dr. Desai.

Several predictors of increased background risk of concerning hyperkalemia were identified. Age greater than 75 years, being on an ACE inhibitor or spironolactone, or a history of diabetes was associated with roughly a twofold increased risk. Baseline renal insufficiency or hyperkalemia conferred a fivefold spike in risk. Candesartan therapy was associated with a threefold increase in risk of hyperkalemia, compared with placebo—but the drug's therapeutic benefit was also consistent across all patient subgroups, including those at high baseline risk for hyperkalemia.

Dr. Gary S. Francis, director of the coronary intensive care unit at the Cleveland Clinic Foundation, called the new results “very important data that have practical implications.” He asked how often potassium should be monitored.

“I would suggest, particularly in patients at high baseline risk, be quite careful to measure serum potassium within a 2- to 3-week period after every dose titration, and again intermittently—even randomly—over the course of follow-up,” he said.

ATLANTA — Candesartan therapy triples the already significant background risk of potentially serious hyperkalemia in patients with heart failure, according to a new secondary analysis of the Candesartan in Heart Failure—Assessment of Reduction in Mortality and Morbidity (CHARM) program.

Periodic monitoring of serum potassium is therefore “critical” in heart failure patients—and not just those on candesartan, Dr. Akshay Desai said at the annual meeting of the American College of Cardiology.

“The estimate from our study is that one would expect roughly 34 excess hyperkalemic events per 1,000 candesartan-treated patients over 3 years. But with careful surveillance of serum potassium, this risk can be substantially reduced. In the trial, seven excess serious events per 1,000 patients were noted over the 3-year duration of follow-up with careful monitoring by study investigators. We feel that this represents the unavoidable risk of candesartan therapy in this population of patients,” said Dr. Desai of Brigham and Women's Hospital, Boston.

To place this risk in perspective, he added, candesartan also prevented 43 cardiovascular death or hospitalization events per 1,000 patients.

The CHARM program involved 7,599 heart failure patients on standard therapy who were randomized in double-blind fashion to candesartan or placebo and followed for just over 3 years with regular monitoring of serum potassium. Candesartan resulted in a significant 16% reduction in the relative risk of the primary end point of cardiovascular death or heart failure hospitalization.

Hyperkalemia is well recognized to be a common and potentially life-threatening complication of treatment with renin-angiotensin-aldosterone system inhibitors. CHARM investigators categorized hyperkalemic events as “serious” if they posed a risk of death or hospitalization, and “concerning” if events were serious or would have become so if not detected early through the monitoring program, with subsequent dose adjustment or drug discontinuation.

The incidence of concerning hyperkalemia during the study was 1.8% in the placebo arm and 5.2% in the candesartan group. Serious hyperkalemic events occurred in 1.1% of the placebo group and 1.8% on candesartan. Of particular clinical relevance was the finding that hyperkalemic events were not confined to the period of candesartan dose titration; they occurred throughout follow-up, although the incidence was greater during titration, said Dr. Desai.

Several predictors of increased background risk of concerning hyperkalemia were identified. Age greater than 75 years, being on an ACE inhibitor or spironolactone, or a history of diabetes was associated with roughly a twofold increased risk. Baseline renal insufficiency or hyperkalemia conferred a fivefold spike in risk. Candesartan therapy was associated with a threefold increase in risk of hyperkalemia, compared with placebo—but the drug's therapeutic benefit was also consistent across all patient subgroups, including those at high baseline risk for hyperkalemia.

Dr. Gary S. Francis, director of the coronary intensive care unit at the Cleveland Clinic Foundation, called the new results “very important data that have practical implications.” He asked how often potassium should be monitored.

“I would suggest, particularly in patients at high baseline risk, be quite careful to measure serum potassium within a 2- to 3-week period after every dose titration, and again intermittently—even randomly—over the course of follow-up,” he said.

ATLANTA — Heart failure patients placed on fixed-dose isosorbide dinitrate-hydralazine derive similar morbidity and mortality benefits regardless of baseline blood pressure, Dr. Inder S. Anand said at the annual meeting of the American College of Cardiology.

This may be because the drug combination possesses the remarkable property of exerting differential effects on blood pressure depending on a patient's baseline blood pressure, according to a new secondary analysis of the African American Heart Failure Trial (A-HeFT).

These A-HeFT data show isosorbide dinitrate-hydralazine (BiDil) lowered blood pressure only in patients with normal or elevated baseline systolic blood pressure. In patients in the lowest quartile of baseline systolic blood pressure—those with a value of 112 mm Hg or less—BiDil actually increased systolic pressure by a mean of 6.4 mm Hg, said Dr. Anand, professor of medicine at the University of Minnesota and director of the heart failure program at the Veterans Affairs Medical Center, Minneapolis.

The new A-HeFT findings are extremely reassuring, he said. Despite the strongly positive primary results of A-HeFT and subsequent Food and Drug Administration approval of BiDil for use in African Americans with moderate to severe heart failure, many physicians have been leery of using the combination. That's because hydralazine has long been recognized to be a potent vasodilator.

There has been concern that the drug would drive blood pressure dangerously low in heart failure patients who have low baseline pressures. This worry stems from the observation that low blood pressure in heart failure patients is a significant predictor of increased morbidity and mortality—unlike in the general population, where lower is better.

A-HeFT, sponsored by NitroMed Inc., involved 1,050 African American heart failure patients randomized in a double-blind fashion to BiDil titrated to a target dose of 120 mg/day of isosorbide dinitrate plus 225 mg/day of hydralazine or to placebo, with state-of-the-art medical management. Overall, BiDil conferred a highly significant 43% reduction in mortality risk during 10 months of follow-up, compared with the 10.2% incidence in the placebo arm, and a 37% decrease in the risk of the combined end point of mortality or first hospitalization for heart failure (N. Engl. J. Med. 2004;351:2049–57).

The new secondary analysis showed that the magnitude of the reductions in mortality and hospitalization was slightly greater, though not significantly, in patients whose baseline systolic blood pressure was below the median of 126 mm Hg than in those above the median, said Dr. Anand.

“These data suggest the combination is well tolerated by heart failure patients with low systolic blood pressure and [that] patients derive similar benefits regardless of baseline blood pressure. Because patients with low blood pressure are at the highest risk of bad outcomes, judicious use of the combination therapy in such patients is likely to lead to substantial benefit,” he said.

Session cochair Dr. Peter E. Carson, of the Veterans Affairs Medical Center in Washington, commented, “The thing that physicians are particularly concerned about when I talk to them about this therapy is the low blood pressure—what will happen if the blood pressure is lowered? You clearly showed that it didn't affect them. That's obviously a very important finding.”

In response to a question, Dr. Anand said hydralazine tolerability and titration were virtually identical in patients in all quartiles of baseline blood pressure. “I was surprised, really, looking at that data. I thought patients with higher blood pressure would get more vasodilation and therefore more headache, but no,” he said.

ATLANTA — Heart failure patients placed on fixed-dose isosorbide dinitrate-hydralazine derive similar morbidity and mortality benefits regardless of baseline blood pressure, Dr. Inder S. Anand said at the annual meeting of the American College of Cardiology.

This may be because the drug combination possesses the remarkable property of exerting differential effects on blood pressure depending on a patient's baseline blood pressure, according to a new secondary analysis of the African American Heart Failure Trial (A-HeFT).

These A-HeFT data show isosorbide dinitrate-hydralazine (BiDil) lowered blood pressure only in patients with normal or elevated baseline systolic blood pressure. In patients in the lowest quartile of baseline systolic blood pressure—those with a value of 112 mm Hg or less—BiDil actually increased systolic pressure by a mean of 6.4 mm Hg, said Dr. Anand, professor of medicine at the University of Minnesota and director of the heart failure program at the Veterans Affairs Medical Center, Minneapolis.

The new A-HeFT findings are extremely reassuring, he said. Despite the strongly positive primary results of A-HeFT and subsequent Food and Drug Administration approval of BiDil for use in African Americans with moderate to severe heart failure, many physicians have been leery of using the combination. That's because hydralazine has long been recognized to be a potent vasodilator.

There has been concern that the drug would drive blood pressure dangerously low in heart failure patients who have low baseline pressures. This worry stems from the observation that low blood pressure in heart failure patients is a significant predictor of increased morbidity and mortality—unlike in the general population, where lower is better.

A-HeFT, sponsored by NitroMed Inc., involved 1,050 African American heart failure patients randomized in a double-blind fashion to BiDil titrated to a target dose of 120 mg/day of isosorbide dinitrate plus 225 mg/day of hydralazine or to placebo, with state-of-the-art medical management. Overall, BiDil conferred a highly significant 43% reduction in mortality risk during 10 months of follow-up, compared with the 10.2% incidence in the placebo arm, and a 37% decrease in the risk of the combined end point of mortality or first hospitalization for heart failure (N. Engl. J. Med. 2004;351:2049–57).

The new secondary analysis showed that the magnitude of the reductions in mortality and hospitalization was slightly greater, though not significantly, in patients whose baseline systolic blood pressure was below the median of 126 mm Hg than in those above the median, said Dr. Anand.

“These data suggest the combination is well tolerated by heart failure patients with low systolic blood pressure and [that] patients derive similar benefits regardless of baseline blood pressure. Because patients with low blood pressure are at the highest risk of bad outcomes, judicious use of the combination therapy in such patients is likely to lead to substantial benefit,” he said.

Session cochair Dr. Peter E. Carson, of the Veterans Affairs Medical Center in Washington, commented, “The thing that physicians are particularly concerned about when I talk to them about this therapy is the low blood pressure—what will happen if the blood pressure is lowered? You clearly showed that it didn't affect them. That's obviously a very important finding.”

In response to a question, Dr. Anand said hydralazine tolerability and titration were virtually identical in patients in all quartiles of baseline blood pressure. “I was surprised, really, looking at that data. I thought patients with higher blood pressure would get more vasodilation and therefore more headache, but no,” he said.

ATLANTA — Heart failure patients placed on fixed-dose isosorbide dinitrate-hydralazine derive similar morbidity and mortality benefits regardless of baseline blood pressure, Dr. Inder S. Anand said at the annual meeting of the American College of Cardiology.

This may be because the drug combination possesses the remarkable property of exerting differential effects on blood pressure depending on a patient's baseline blood pressure, according to a new secondary analysis of the African American Heart Failure Trial (A-HeFT).

These A-HeFT data show isosorbide dinitrate-hydralazine (BiDil) lowered blood pressure only in patients with normal or elevated baseline systolic blood pressure. In patients in the lowest quartile of baseline systolic blood pressure—those with a value of 112 mm Hg or less—BiDil actually increased systolic pressure by a mean of 6.4 mm Hg, said Dr. Anand, professor of medicine at the University of Minnesota and director of the heart failure program at the Veterans Affairs Medical Center, Minneapolis.

The new A-HeFT findings are extremely reassuring, he said. Despite the strongly positive primary results of A-HeFT and subsequent Food and Drug Administration approval of BiDil for use in African Americans with moderate to severe heart failure, many physicians have been leery of using the combination. That's because hydralazine has long been recognized to be a potent vasodilator.

There has been concern that the drug would drive blood pressure dangerously low in heart failure patients who have low baseline pressures. This worry stems from the observation that low blood pressure in heart failure patients is a significant predictor of increased morbidity and mortality—unlike in the general population, where lower is better.

A-HeFT, sponsored by NitroMed Inc., involved 1,050 African American heart failure patients randomized in a double-blind fashion to BiDil titrated to a target dose of 120 mg/day of isosorbide dinitrate plus 225 mg/day of hydralazine or to placebo, with state-of-the-art medical management. Overall, BiDil conferred a highly significant 43% reduction in mortality risk during 10 months of follow-up, compared with the 10.2% incidence in the placebo arm, and a 37% decrease in the risk of the combined end point of mortality or first hospitalization for heart failure (N. Engl. J. Med. 2004;351:2049–57).

The new secondary analysis showed that the magnitude of the reductions in mortality and hospitalization was slightly greater, though not significantly, in patients whose baseline systolic blood pressure was below the median of 126 mm Hg than in those above the median, said Dr. Anand.

“These data suggest the combination is well tolerated by heart failure patients with low systolic blood pressure and [that] patients derive similar benefits regardless of baseline blood pressure. Because patients with low blood pressure are at the highest risk of bad outcomes, judicious use of the combination therapy in such patients is likely to lead to substantial benefit,” he said.

Session cochair Dr. Peter E. Carson, of the Veterans Affairs Medical Center in Washington, commented, “The thing that physicians are particularly concerned about when I talk to them about this therapy is the low blood pressure—what will happen if the blood pressure is lowered? You clearly showed that it didn't affect them. That's obviously a very important finding.”

In response to a question, Dr. Anand said hydralazine tolerability and titration were virtually identical in patients in all quartiles of baseline blood pressure. “I was surprised, really, looking at that data. I thought patients with higher blood pressure would get more vasodilation and therefore more headache, but no,” he said.

ATLANTA — It is possible to preoperatively identify a small subgroup of candidates for left ventricular assist device implantation as destination therapy, that is, as a permanent alternative to heart transplantation because their poor outcomes would render a transplant futile, said Dr. Katherine Lietz at the annual meeting of the American College of Cardiology.

The long-term outcomes for such a subgroup are remarkably good, she said.

Dr. Lietz presented an analysis of the largest population of LVAD recipients as destination therapy ever described: 311 patients who received the Thoratec HeartMate XVE at 65 hospitals in the United States and who were enrolled in the Food and Drug Administration-mandated Thoratec Destination Therapy Registry, through which they have been followed for a median of 15 months.

The overall group had a 1-month survival of 86%, a 1-year survival of 57%, and a 2-year survival of 38%. But those figures mask a wide range of outcomes. For example, 26% of patients died before they were able to leave the hospital after surgery, with the causes of death being sepsis, multiorgan failure, and right heart failure. The fact that none died of LVAD failure in the first year suggests that patient selection plays a key role in early postoperative outcomes, said Dr. Lietz of the University of Minnesota Medical Center, Minneapolis.

She and her coworkers therefore sought to develop a prospective tool for preoperative risk stratification. They evaluated 65 variables for potential inclusion.

In a multivariate analysis, the significant predictors of poor outcome included malnutrition as reflected by a serum albumin below 3.3 g/dL, low pulmonary artery pressures, a need for ventilatory support, severe renal dysfunction with a creatinine clearance below 30 mL/min, anemia, coagulopathies, any degree of hepatic dysfunction, and an elevated WBC count and other signs and symptoms of infection. Patients who were not on an inotropic agent, a β-blocker, or an ACE inhibitor just before implantation were also at higher risk for early in-hospital mortality.

The investigators assigned each risk factor a weighted relative value and summed them to obtain a cumulative risk score for each patient. On the basis of those scores, they divided the registry cohort into risk categories for in-hospital mortality. The rate of survival to hospital discharge was 100% in the low-risk group, 95% in those at medium risk, 68% in the high-risk group, and 25% in the very-high-risk population.

Overall, 1-year survival was 94%, 73%, and 53% in the low-, medium-, and high-risk groups, respectively, compared with 6% in the very-high-risk subgroup.

This very-high-risk subgroup was composed of just 12% of the total population. By excluding patients in this group, 1-year survival in the remaining 88% of patients in the combined low-, medium-, and high-risk groups was 70%, with a 2-year survival of 50%.

Dr. Lietz stressed that she does not believe that candidates with a very-high-risk score should necessarily be denied destination therapy with an LVAD. After all, many of the risk factors are modifiable—for example, nutritional status and coagulopathies—and could be addressed before surgery to move the patient out of the least-favorable category.

Dr. Marvin A. Konstam, professor of medicine at Tufts University, Boston, and chief of cardiology at New England Medical Center, noted that the decision to resort to destination therapy is driven only in part by the likelihood of device therapy's long-term success. Another key factor in the equation is the patient's prognosis on medical therapy.

“If we can identify a subgroup in which the risk with medical therapy is highest and yet survival with an LVAD is adequate, those might be the ideal destination therapy candidates,” he said.

LVADs are most often implanted as a temporary bridge to heart transplantation in patients awaiting a donor organ. But in November 2002, the FDA approved the use of the Thoratec HeartMate XVE as destination therapy in response to the positive results of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial.

Medicare covers the therapy in patients with class IV, end-stage heart failure who otherwise have a life expectancy of less than 2 years and are not candidates for transplantation because of advanced age or comorbidities.

ATLANTA — It is possible to preoperatively identify a small subgroup of candidates for left ventricular assist device implantation as destination therapy, that is, as a permanent alternative to heart transplantation because their poor outcomes would render a transplant futile, said Dr. Katherine Lietz at the annual meeting of the American College of Cardiology.

The long-term outcomes for such a subgroup are remarkably good, she said.

Dr. Lietz presented an analysis of the largest population of LVAD recipients as destination therapy ever described: 311 patients who received the Thoratec HeartMate XVE at 65 hospitals in the United States and who were enrolled in the Food and Drug Administration-mandated Thoratec Destination Therapy Registry, through which they have been followed for a median of 15 months.

The overall group had a 1-month survival of 86%, a 1-year survival of 57%, and a 2-year survival of 38%. But those figures mask a wide range of outcomes. For example, 26% of patients died before they were able to leave the hospital after surgery, with the causes of death being sepsis, multiorgan failure, and right heart failure. The fact that none died of LVAD failure in the first year suggests that patient selection plays a key role in early postoperative outcomes, said Dr. Lietz of the University of Minnesota Medical Center, Minneapolis.

She and her coworkers therefore sought to develop a prospective tool for preoperative risk stratification. They evaluated 65 variables for potential inclusion.

In a multivariate analysis, the significant predictors of poor outcome included malnutrition as reflected by a serum albumin below 3.3 g/dL, low pulmonary artery pressures, a need for ventilatory support, severe renal dysfunction with a creatinine clearance below 30 mL/min, anemia, coagulopathies, any degree of hepatic dysfunction, and an elevated WBC count and other signs and symptoms of infection. Patients who were not on an inotropic agent, a β-blocker, or an ACE inhibitor just before implantation were also at higher risk for early in-hospital mortality.

The investigators assigned each risk factor a weighted relative value and summed them to obtain a cumulative risk score for each patient. On the basis of those scores, they divided the registry cohort into risk categories for in-hospital mortality. The rate of survival to hospital discharge was 100% in the low-risk group, 95% in those at medium risk, 68% in the high-risk group, and 25% in the very-high-risk population.

Overall, 1-year survival was 94%, 73%, and 53% in the low-, medium-, and high-risk groups, respectively, compared with 6% in the very-high-risk subgroup.

This very-high-risk subgroup was composed of just 12% of the total population. By excluding patients in this group, 1-year survival in the remaining 88% of patients in the combined low-, medium-, and high-risk groups was 70%, with a 2-year survival of 50%.

Dr. Lietz stressed that she does not believe that candidates with a very-high-risk score should necessarily be denied destination therapy with an LVAD. After all, many of the risk factors are modifiable—for example, nutritional status and coagulopathies—and could be addressed before surgery to move the patient out of the least-favorable category.

Dr. Marvin A. Konstam, professor of medicine at Tufts University, Boston, and chief of cardiology at New England Medical Center, noted that the decision to resort to destination therapy is driven only in part by the likelihood of device therapy's long-term success. Another key factor in the equation is the patient's prognosis on medical therapy.

“If we can identify a subgroup in which the risk with medical therapy is highest and yet survival with an LVAD is adequate, those might be the ideal destination therapy candidates,” he said.

LVADs are most often implanted as a temporary bridge to heart transplantation in patients awaiting a donor organ. But in November 2002, the FDA approved the use of the Thoratec HeartMate XVE as destination therapy in response to the positive results of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial.

Medicare covers the therapy in patients with class IV, end-stage heart failure who otherwise have a life expectancy of less than 2 years and are not candidates for transplantation because of advanced age or comorbidities.

ATLANTA — It is possible to preoperatively identify a small subgroup of candidates for left ventricular assist device implantation as destination therapy, that is, as a permanent alternative to heart transplantation because their poor outcomes would render a transplant futile, said Dr. Katherine Lietz at the annual meeting of the American College of Cardiology.

The long-term outcomes for such a subgroup are remarkably good, she said.

Dr. Lietz presented an analysis of the largest population of LVAD recipients as destination therapy ever described: 311 patients who received the Thoratec HeartMate XVE at 65 hospitals in the United States and who were enrolled in the Food and Drug Administration-mandated Thoratec Destination Therapy Registry, through which they have been followed for a median of 15 months.

The overall group had a 1-month survival of 86%, a 1-year survival of 57%, and a 2-year survival of 38%. But those figures mask a wide range of outcomes. For example, 26% of patients died before they were able to leave the hospital after surgery, with the causes of death being sepsis, multiorgan failure, and right heart failure. The fact that none died of LVAD failure in the first year suggests that patient selection plays a key role in early postoperative outcomes, said Dr. Lietz of the University of Minnesota Medical Center, Minneapolis.

She and her coworkers therefore sought to develop a prospective tool for preoperative risk stratification. They evaluated 65 variables for potential inclusion.

In a multivariate analysis, the significant predictors of poor outcome included malnutrition as reflected by a serum albumin below 3.3 g/dL, low pulmonary artery pressures, a need for ventilatory support, severe renal dysfunction with a creatinine clearance below 30 mL/min, anemia, coagulopathies, any degree of hepatic dysfunction, and an elevated WBC count and other signs and symptoms of infection. Patients who were not on an inotropic agent, a β-blocker, or an ACE inhibitor just before implantation were also at higher risk for early in-hospital mortality.

The investigators assigned each risk factor a weighted relative value and summed them to obtain a cumulative risk score for each patient. On the basis of those scores, they divided the registry cohort into risk categories for in-hospital mortality. The rate of survival to hospital discharge was 100% in the low-risk group, 95% in those at medium risk, 68% in the high-risk group, and 25% in the very-high-risk population.

Overall, 1-year survival was 94%, 73%, and 53% in the low-, medium-, and high-risk groups, respectively, compared with 6% in the very-high-risk subgroup.

This very-high-risk subgroup was composed of just 12% of the total population. By excluding patients in this group, 1-year survival in the remaining 88% of patients in the combined low-, medium-, and high-risk groups was 70%, with a 2-year survival of 50%.

Dr. Lietz stressed that she does not believe that candidates with a very-high-risk score should necessarily be denied destination therapy with an LVAD. After all, many of the risk factors are modifiable—for example, nutritional status and coagulopathies—and could be addressed before surgery to move the patient out of the least-favorable category.

Dr. Marvin A. Konstam, professor of medicine at Tufts University, Boston, and chief of cardiology at New England Medical Center, noted that the decision to resort to destination therapy is driven only in part by the likelihood of device therapy's long-term success. Another key factor in the equation is the patient's prognosis on medical therapy.

“If we can identify a subgroup in which the risk with medical therapy is highest and yet survival with an LVAD is adequate, those might be the ideal destination therapy candidates,” he said.

LVADs are most often implanted as a temporary bridge to heart transplantation in patients awaiting a donor organ. But in November 2002, the FDA approved the use of the Thoratec HeartMate XVE as destination therapy in response to the positive results of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial.

Medicare covers the therapy in patients with class IV, end-stage heart failure who otherwise have a life expectancy of less than 2 years and are not candidates for transplantation because of advanced age or comorbidities.

MONTREAL — Obese patients often have a constellation of physiological problems that together can lead to a mistaken diagnosis of pulmonary artery hypertension, according to researchers at Duke University Medical Center in Durham, N.C.

The presence of exertional dyspnea in these patients often leads to an echocardiogram and a finding of elevated right ventricular systolic pressure.

“Often the pressure is just mildly elevated, and these patients don't really have pulmonary arterial hypertension but are referred for evaluation anyway,” Dr. Terry A. Fortin said at the annual meeting of the American College of Chest Physicians.

To assess diagnostic strategies for pulmonary arterial hypertension (PAH) in this often very symptomatic population, Dr. Fortin and her colleagues at Duke University retrospectively assessed consecutive cardiac catheterization data on patients referred for suspected PAH.

Suspected PAH was defined as mean pulmonary arterial pressure (mPAP) greater than 25 mm/Hg, pulmonary capillary wedge pressure (PCWP) less than 15 mm/Hg, and pulmonary vascular resistance (PVR) greater than 3 Wood units. Patients with left ventricular systolic dysfunction, PAH clearly associated with a known syndrome, or significant valve or lung disease of sufficient severity to explain PH were excluded. That left 78 obese patients with mild pulmonary hypertension (PH) with mPAP greater than 25 mm/Hg and PVR less than 5 Wood units, said Dr. Fortin of Duke University Medical Center.

Of those 78 patients, 40 had baseline syndromes or conditions that the investigators believed adequately explained the patients' PH after workup. Those conditions included connective tissue disease, congenital heart disease, chronic thromboembolic disease, portopulmonary disease, severe lung disease, high-output arteriovenous shunts, and left-sided valve disease.

Eliminating these patients left 38 patients with elevated mPAP associated with a constellation of factors that together resulted in PH, although maybe not PAH, Dr. Fortin said.

Most were women with a mean age of 60 years. All were hypertensive, and virtually all had a body mass index greater than 30; half had a body mass index (BMI) greater than 40. Nearly two-thirds had diabetes and/or a sleep disorder.

“The precatheterization diagnostic tests often showed elevated right ventricular systolic pressures on referral cardiac echo, and that was typically the reason that the patients were sent to us,” Dr. Fortin explained. Many of the patients did have increased artery sizes, and their right atrium size or decreased contractility in the right ventricle was of concern. About half the patients were hypoxemic, and some were hypercarbic, “which is not necessarily what we would expect in pulmonary hypertension,” she added.

Low lung volume was common, and many patients had reduced diffusion capacity of carbon monoxide (DLCO). Two patients had only increased right ventricular systolic pressures.

“Looking at the cardiac cath data, PVRs were not quite 3 [Wood units] in most patients, and if you break them down into those with enlarged and normal right ventricles, they're slightly different, but not statistically so,” Dr. Fortin said. The investigators also found a slight but statistically nonsignificant difference in mean pulmonary pressures, with a predominance of elevated pressures—as expected in bigger right ventricles. Overall, the patients had normal cardiac indices and were not very sick.

Only one patient had pulmonary arterial hypertension based upon a PCWP less than 15 mm/Hg and a PVR greater than 3, Dr. Fortin said. Hypoxemia, hypercarbia, low total lung capacity, and DLCO were all related to obesity, hypoventilation, and sleep disorders, she added.

“Lest you think that obese people do not ever have pulmonary hypertension, I was quickly able to glean 13 patients … who were morbidly obese with BMIs greater than 40 who were seen in our clinic,” Dr. Fortin said. “All had mPAPs greater than 25 with elevated pulmonary vascular resistances. In fact, their average pulmonary artery pressure was 60, and their PVR was 12, while their cardiac indices were very low; these were very sick patients.”

The study's researchers concluded that a number of factors can contribute to a mistaken diagnosis of PAH. They include systemic hypertension, obesity, sleep-disordered breathing and hypoventilation, and elevated pulmonary capillary wedge pressure.

“It should not be assumed that patients with an elevated right ventricular systolic pressure by echo have pulmonary arterial hypertension,” Dr. Fortin cautioned. “Pulmonary capillary wedge pressure and diastolic dysfunction may be causative.”

Aggressive management of weight, sleep disorders, hypertension, hypoxemia, and diabetes may limit the development of diastolic dysfunction and secondary pulmonary hypertension, though that's easier said than done, she added.

“Patients with this complex of disorders often have findings similar to those in full-blown PAH, and thus cardiac catheterization is necessary to help sort this out,” Dr. Fortin said. “I think that diagnostic testing also should definitely include sleep studies, as 70% of these patients had sleep disorders that were not necessarily diagnosed at the time of presentation.”

It's not necessary to go right to a diagnostic test, Dr. Fortin said, “as long as you're following the patient carefully; try to fix these other factors first before going to cardiac catheterization.”

'It should not be assumed that patients with an elevated right ventricular systolic pressure by echo' have PAH. DR. FORTIN

MONTREAL — Obese patients often have a constellation of physiological problems that together can lead to a mistaken diagnosis of pulmonary artery hypertension, according to researchers at Duke University Medical Center in Durham, N.C.

The presence of exertional dyspnea in these patients often leads to an echocardiogram and a finding of elevated right ventricular systolic pressure.

“Often the pressure is just mildly elevated, and these patients don't really have pulmonary arterial hypertension but are referred for evaluation anyway,” Dr. Terry A. Fortin said at the annual meeting of the American College of Chest Physicians.

To assess diagnostic strategies for pulmonary arterial hypertension (PAH) in this often very symptomatic population, Dr. Fortin and her colleagues at Duke University retrospectively assessed consecutive cardiac catheterization data on patients referred for suspected PAH.

Suspected PAH was defined as mean pulmonary arterial pressure (mPAP) greater than 25 mm/Hg, pulmonary capillary wedge pressure (PCWP) less than 15 mm/Hg, and pulmonary vascular resistance (PVR) greater than 3 Wood units. Patients with left ventricular systolic dysfunction, PAH clearly associated with a known syndrome, or significant valve or lung disease of sufficient severity to explain PH were excluded. That left 78 obese patients with mild pulmonary hypertension (PH) with mPAP greater than 25 mm/Hg and PVR less than 5 Wood units, said Dr. Fortin of Duke University Medical Center.

Of those 78 patients, 40 had baseline syndromes or conditions that the investigators believed adequately explained the patients' PH after workup. Those conditions included connective tissue disease, congenital heart disease, chronic thromboembolic disease, portopulmonary disease, severe lung disease, high-output arteriovenous shunts, and left-sided valve disease.

Eliminating these patients left 38 patients with elevated mPAP associated with a constellation of factors that together resulted in PH, although maybe not PAH, Dr. Fortin said.

Most were women with a mean age of 60 years. All were hypertensive, and virtually all had a body mass index greater than 30; half had a body mass index (BMI) greater than 40. Nearly two-thirds had diabetes and/or a sleep disorder.

“The precatheterization diagnostic tests often showed elevated right ventricular systolic pressures on referral cardiac echo, and that was typically the reason that the patients were sent to us,” Dr. Fortin explained. Many of the patients did have increased artery sizes, and their right atrium size or decreased contractility in the right ventricle was of concern. About half the patients were hypoxemic, and some were hypercarbic, “which is not necessarily what we would expect in pulmonary hypertension,” she added.

Low lung volume was common, and many patients had reduced diffusion capacity of carbon monoxide (DLCO). Two patients had only increased right ventricular systolic pressures.

“Looking at the cardiac cath data, PVRs were not quite 3 [Wood units] in most patients, and if you break them down into those with enlarged and normal right ventricles, they're slightly different, but not statistically so,” Dr. Fortin said. The investigators also found a slight but statistically nonsignificant difference in mean pulmonary pressures, with a predominance of elevated pressures—as expected in bigger right ventricles. Overall, the patients had normal cardiac indices and were not very sick.

Only one patient had pulmonary arterial hypertension based upon a PCWP less than 15 mm/Hg and a PVR greater than 3, Dr. Fortin said. Hypoxemia, hypercarbia, low total lung capacity, and DLCO were all related to obesity, hypoventilation, and sleep disorders, she added.

“Lest you think that obese people do not ever have pulmonary hypertension, I was quickly able to glean 13 patients … who were morbidly obese with BMIs greater than 40 who were seen in our clinic,” Dr. Fortin said. “All had mPAPs greater than 25 with elevated pulmonary vascular resistances. In fact, their average pulmonary artery pressure was 60, and their PVR was 12, while their cardiac indices were very low; these were very sick patients.”

The study's researchers concluded that a number of factors can contribute to a mistaken diagnosis of PAH. They include systemic hypertension, obesity, sleep-disordered breathing and hypoventilation, and elevated pulmonary capillary wedge pressure.

“It should not be assumed that patients with an elevated right ventricular systolic pressure by echo have pulmonary arterial hypertension,” Dr. Fortin cautioned. “Pulmonary capillary wedge pressure and diastolic dysfunction may be causative.”

Aggressive management of weight, sleep disorders, hypertension, hypoxemia, and diabetes may limit the development of diastolic dysfunction and secondary pulmonary hypertension, though that's easier said than done, she added.

“Patients with this complex of disorders often have findings similar to those in full-blown PAH, and thus cardiac catheterization is necessary to help sort this out,” Dr. Fortin said. “I think that diagnostic testing also should definitely include sleep studies, as 70% of these patients had sleep disorders that were not necessarily diagnosed at the time of presentation.”

It's not necessary to go right to a diagnostic test, Dr. Fortin said, “as long as you're following the patient carefully; try to fix these other factors first before going to cardiac catheterization.”

'It should not be assumed that patients with an elevated right ventricular systolic pressure by echo' have PAH. DR. FORTIN

MONTREAL — Obese patients often have a constellation of physiological problems that together can lead to a mistaken diagnosis of pulmonary artery hypertension, according to researchers at Duke University Medical Center in Durham, N.C.

The presence of exertional dyspnea in these patients often leads to an echocardiogram and a finding of elevated right ventricular systolic pressure.

“Often the pressure is just mildly elevated, and these patients don't really have pulmonary arterial hypertension but are referred for evaluation anyway,” Dr. Terry A. Fortin said at the annual meeting of the American College of Chest Physicians.

To assess diagnostic strategies for pulmonary arterial hypertension (PAH) in this often very symptomatic population, Dr. Fortin and her colleagues at Duke University retrospectively assessed consecutive cardiac catheterization data on patients referred for suspected PAH.

Suspected PAH was defined as mean pulmonary arterial pressure (mPAP) greater than 25 mm/Hg, pulmonary capillary wedge pressure (PCWP) less than 15 mm/Hg, and pulmonary vascular resistance (PVR) greater than 3 Wood units. Patients with left ventricular systolic dysfunction, PAH clearly associated with a known syndrome, or significant valve or lung disease of sufficient severity to explain PH were excluded. That left 78 obese patients with mild pulmonary hypertension (PH) with mPAP greater than 25 mm/Hg and PVR less than 5 Wood units, said Dr. Fortin of Duke University Medical Center.

Of those 78 patients, 40 had baseline syndromes or conditions that the investigators believed adequately explained the patients' PH after workup. Those conditions included connective tissue disease, congenital heart disease, chronic thromboembolic disease, portopulmonary disease, severe lung disease, high-output arteriovenous shunts, and left-sided valve disease.

Eliminating these patients left 38 patients with elevated mPAP associated with a constellation of factors that together resulted in PH, although maybe not PAH, Dr. Fortin said.

Most were women with a mean age of 60 years. All were hypertensive, and virtually all had a body mass index greater than 30; half had a body mass index (BMI) greater than 40. Nearly two-thirds had diabetes and/or a sleep disorder.

“The precatheterization diagnostic tests often showed elevated right ventricular systolic pressures on referral cardiac echo, and that was typically the reason that the patients were sent to us,” Dr. Fortin explained. Many of the patients did have increased artery sizes, and their right atrium size or decreased contractility in the right ventricle was of concern. About half the patients were hypoxemic, and some were hypercarbic, “which is not necessarily what we would expect in pulmonary hypertension,” she added.

Low lung volume was common, and many patients had reduced diffusion capacity of carbon monoxide (DLCO). Two patients had only increased right ventricular systolic pressures.

“Looking at the cardiac cath data, PVRs were not quite 3 [Wood units] in most patients, and if you break them down into those with enlarged and normal right ventricles, they're slightly different, but not statistically so,” Dr. Fortin said. The investigators also found a slight but statistically nonsignificant difference in mean pulmonary pressures, with a predominance of elevated pressures—as expected in bigger right ventricles. Overall, the patients had normal cardiac indices and were not very sick.

Only one patient had pulmonary arterial hypertension based upon a PCWP less than 15 mm/Hg and a PVR greater than 3, Dr. Fortin said. Hypoxemia, hypercarbia, low total lung capacity, and DLCO were all related to obesity, hypoventilation, and sleep disorders, she added.

“Lest you think that obese people do not ever have pulmonary hypertension, I was quickly able to glean 13 patients … who were morbidly obese with BMIs greater than 40 who were seen in our clinic,” Dr. Fortin said. “All had mPAPs greater than 25 with elevated pulmonary vascular resistances. In fact, their average pulmonary artery pressure was 60, and their PVR was 12, while their cardiac indices were very low; these were very sick patients.”

The study's researchers concluded that a number of factors can contribute to a mistaken diagnosis of PAH. They include systemic hypertension, obesity, sleep-disordered breathing and hypoventilation, and elevated pulmonary capillary wedge pressure.

“It should not be assumed that patients with an elevated right ventricular systolic pressure by echo have pulmonary arterial hypertension,” Dr. Fortin cautioned. “Pulmonary capillary wedge pressure and diastolic dysfunction may be causative.”

Aggressive management of weight, sleep disorders, hypertension, hypoxemia, and diabetes may limit the development of diastolic dysfunction and secondary pulmonary hypertension, though that's easier said than done, she added.

“Patients with this complex of disorders often have findings similar to those in full-blown PAH, and thus cardiac catheterization is necessary to help sort this out,” Dr. Fortin said. “I think that diagnostic testing also should definitely include sleep studies, as 70% of these patients had sleep disorders that were not necessarily diagnosed at the time of presentation.”

It's not necessary to go right to a diagnostic test, Dr. Fortin said, “as long as you're following the patient carefully; try to fix these other factors first before going to cardiac catheterization.”

'It should not be assumed that patients with an elevated right ventricular systolic pressure by echo' have PAH. DR. FORTIN

SNOWMASS, COLO. — Treatment options in pulmonary arterial hypertension have significantly improved in recent months with the marketing of two useful new agents: oral sildenafil and inhaled iloprost, Dr. Carole A. Warnes said at a conference that was sponsored by the Society for Cardiovascular Angiography and Interventions.

Iloprost (Ventavis), a prostacyclin analog, has several advantages over other available therapies. The inhaled route of administration makes iloprost a topical therapy that selectively causes vasodilation in the pulmonary circulation while minimizing systemic drug effects.

Inhaled therapy also promotes drug deposition in areas of the lung that are well ventilated, with resultant reduced ventilation/perfusion mismatch. “This might be important in patients with associated parenchymal lung disease,” noted Dr. Warnes, professor of medicine at the Mayo Medical School, Rochester, Minn.

A source of frustration for many physicians caring for patients with pulmonary arterial hypertension (PAH) is that iloprost, sildenafil, and the other drugs of proven efficacy result in only a modest, albeit clinically meaningful, improvement in 6-minute walk distance, the standard efficacy measure in clinical trials.

For example, in the pivotal randomized, placebo-controlled, double-blind crossover trial—Sildenafil Use in Pulmonary Arterial Hypertension (SUPER)—12 weeks of sildenafil (Revatio) at 20 mg t.i.d. resulted in a mean placebo-corrected 45-meter gain in 6-minute walk distance, compared with baseline (N. Engl. J. Med. 2005;353:2148–57). Twelve weeks of iloprost brought a 36-meter gain in another randomized trial. An ongoing major trial combining the two agents with their differing mechanisms of action aims to learn whether efficacy is enhanced.

Recent developments in PAH involved a rat model of the disease, in which inhaled iloprost induced remodeling of the vascular structure of the pulmonary arteries (Am. J. Respir. Crit. Care Med. 2005;172:358–63). The prostacyclin analog resulted in reduced right ventricular systolic pressure, regression of right ventricular hypertrophy, attenuation of matrix metalloproteinase-2 and —9 expression, and decreases in the degree of muscularization and the medial wall thickness of the small pulmonary arteries in this German study.

That's a first for any drug. The animal data raise the possibility that damage to the pulmonary vascular circuit in patients with PAH may not be irreversible. “There is a structural change in the rat model. Perhaps we can regress PAH, not just hemodynamically, but structurally,” Dr. Warnes said.

But inhaled iloprost is a complicated therapy. Patients self-administer it using a special device six to nine times per day, with each session taking about 10 minutes.

Iloprost is approved for patients with New York Heart Association functional class III or IV PAH.

Sildenafil, on the other hand, is the first oral agent approved for early-stage PAH. In the SUPER trial, it not only improved 6-minute walk distance by 13% over baseline, it also lowered pulmonary artery pressure. Improvements were maintained at 12 months.

The near-term drug development pipeline includes more endothelin-receptor antagonists and prostanoids. But there is also an opportunity to test entirely new therapeutic approaches targeting abnormalities in PAH that have not yet been addressed, Dr. Warnes continued.

For example, PAH is associated with serotonin transporter-gene polymorphisms and increased circulating serotonin levels, raising the possibility that SSRIs might be beneficial. Potassium channels are downregulated on the pulmonary artery smooth muscle cells of patients with PAH, suggesting a therapeutic role for a potassium channel opener. The disease is also marked by increased circulating cytokines, autoantibodies, and chemokine expression, pointing to a potential application for immunosuppressive agents.

Patients with PAH have reduced vascular levels of vasoactive intestinal peptide; perhaps administration of vasoactive intestinal peptides would provide benefit. PAH is also marked by increased vascular endothelial growth factor activity, which could be addressed by antiangiogenesis agents. And even though warfarin has been standard therapy in PAH for decades, the effect of aspirin has never been studied, Dr. Warnes noted.

INHALED THERAPY DEPOSITS THE DRUG IN WELL-VENTILATED AREAS OF THE LUNG, REDUCING VENTILATION-PERFUSION MISMATCH. Dr. Warnes

SNOWMASS, COLO. — Treatment options in pulmonary arterial hypertension have significantly improved in recent months with the marketing of two useful new agents: oral sildenafil and inhaled iloprost, Dr. Carole A. Warnes said at a conference that was sponsored by the Society for Cardiovascular Angiography and Interventions.

Iloprost (Ventavis), a prostacyclin analog, has several advantages over other available therapies. The inhaled route of administration makes iloprost a topical therapy that selectively causes vasodilation in the pulmonary circulation while minimizing systemic drug effects.

Inhaled therapy also promotes drug deposition in areas of the lung that are well ventilated, with resultant reduced ventilation/perfusion mismatch. “This might be important in patients with associated parenchymal lung disease,” noted Dr. Warnes, professor of medicine at the Mayo Medical School, Rochester, Minn.

A source of frustration for many physicians caring for patients with pulmonary arterial hypertension (PAH) is that iloprost, sildenafil, and the other drugs of proven efficacy result in only a modest, albeit clinically meaningful, improvement in 6-minute walk distance, the standard efficacy measure in clinical trials.

For example, in the pivotal randomized, placebo-controlled, double-blind crossover trial—Sildenafil Use in Pulmonary Arterial Hypertension (SUPER)—12 weeks of sildenafil (Revatio) at 20 mg t.i.d. resulted in a mean placebo-corrected 45-meter gain in 6-minute walk distance, compared with baseline (N. Engl. J. Med. 2005;353:2148–57). Twelve weeks of iloprost brought a 36-meter gain in another randomized trial. An ongoing major trial combining the two agents with their differing mechanisms of action aims to learn whether efficacy is enhanced.

Recent developments in PAH involved a rat model of the disease, in which inhaled iloprost induced remodeling of the vascular structure of the pulmonary arteries (Am. J. Respir. Crit. Care Med. 2005;172:358–63). The prostacyclin analog resulted in reduced right ventricular systolic pressure, regression of right ventricular hypertrophy, attenuation of matrix metalloproteinase-2 and —9 expression, and decreases in the degree of muscularization and the medial wall thickness of the small pulmonary arteries in this German study.

That's a first for any drug. The animal data raise the possibility that damage to the pulmonary vascular circuit in patients with PAH may not be irreversible. “There is a structural change in the rat model. Perhaps we can regress PAH, not just hemodynamically, but structurally,” Dr. Warnes said.

But inhaled iloprost is a complicated therapy. Patients self-administer it using a special device six to nine times per day, with each session taking about 10 minutes.

Iloprost is approved for patients with New York Heart Association functional class III or IV PAH.

Sildenafil, on the other hand, is the first oral agent approved for early-stage PAH. In the SUPER trial, it not only improved 6-minute walk distance by 13% over baseline, it also lowered pulmonary artery pressure. Improvements were maintained at 12 months.

The near-term drug development pipeline includes more endothelin-receptor antagonists and prostanoids. But there is also an opportunity to test entirely new therapeutic approaches targeting abnormalities in PAH that have not yet been addressed, Dr. Warnes continued.

For example, PAH is associated with serotonin transporter-gene polymorphisms and increased circulating serotonin levels, raising the possibility that SSRIs might be beneficial. Potassium channels are downregulated on the pulmonary artery smooth muscle cells of patients with PAH, suggesting a therapeutic role for a potassium channel opener. The disease is also marked by increased circulating cytokines, autoantibodies, and chemokine expression, pointing to a potential application for immunosuppressive agents.

Patients with PAH have reduced vascular levels of vasoactive intestinal peptide; perhaps administration of vasoactive intestinal peptides would provide benefit. PAH is also marked by increased vascular endothelial growth factor activity, which could be addressed by antiangiogenesis agents. And even though warfarin has been standard therapy in PAH for decades, the effect of aspirin has never been studied, Dr. Warnes noted.

INHALED THERAPY DEPOSITS THE DRUG IN WELL-VENTILATED AREAS OF THE LUNG, REDUCING VENTILATION-PERFUSION MISMATCH. Dr. Warnes

SNOWMASS, COLO. — Treatment options in pulmonary arterial hypertension have significantly improved in recent months with the marketing of two useful new agents: oral sildenafil and inhaled iloprost, Dr. Carole A. Warnes said at a conference that was sponsored by the Society for Cardiovascular Angiography and Interventions.

Iloprost (Ventavis), a prostacyclin analog, has several advantages over other available therapies. The inhaled route of administration makes iloprost a topical therapy that selectively causes vasodilation in the pulmonary circulation while minimizing systemic drug effects.

Inhaled therapy also promotes drug deposition in areas of the lung that are well ventilated, with resultant reduced ventilation/perfusion mismatch. “This might be important in patients with associated parenchymal lung disease,” noted Dr. Warnes, professor of medicine at the Mayo Medical School, Rochester, Minn.

A source of frustration for many physicians caring for patients with pulmonary arterial hypertension (PAH) is that iloprost, sildenafil, and the other drugs of proven efficacy result in only a modest, albeit clinically meaningful, improvement in 6-minute walk distance, the standard efficacy measure in clinical trials.

For example, in the pivotal randomized, placebo-controlled, double-blind crossover trial—Sildenafil Use in Pulmonary Arterial Hypertension (SUPER)—12 weeks of sildenafil (Revatio) at 20 mg t.i.d. resulted in a mean placebo-corrected 45-meter gain in 6-minute walk distance, compared with baseline (N. Engl. J. Med. 2005;353:2148–57). Twelve weeks of iloprost brought a 36-meter gain in another randomized trial. An ongoing major trial combining the two agents with their differing mechanisms of action aims to learn whether efficacy is enhanced.

Recent developments in PAH involved a rat model of the disease, in which inhaled iloprost induced remodeling of the vascular structure of the pulmonary arteries (Am. J. Respir. Crit. Care Med. 2005;172:358–63). The prostacyclin analog resulted in reduced right ventricular systolic pressure, regression of right ventricular hypertrophy, attenuation of matrix metalloproteinase-2 and —9 expression, and decreases in the degree of muscularization and the medial wall thickness of the small pulmonary arteries in this German study.

That's a first for any drug. The animal data raise the possibility that damage to the pulmonary vascular circuit in patients with PAH may not be irreversible. “There is a structural change in the rat model. Perhaps we can regress PAH, not just hemodynamically, but structurally,” Dr. Warnes said.

But inhaled iloprost is a complicated therapy. Patients self-administer it using a special device six to nine times per day, with each session taking about 10 minutes.

Iloprost is approved for patients with New York Heart Association functional class III or IV PAH.

Sildenafil, on the other hand, is the first oral agent approved for early-stage PAH. In the SUPER trial, it not only improved 6-minute walk distance by 13% over baseline, it also lowered pulmonary artery pressure. Improvements were maintained at 12 months.

The near-term drug development pipeline includes more endothelin-receptor antagonists and prostanoids. But there is also an opportunity to test entirely new therapeutic approaches targeting abnormalities in PAH that have not yet been addressed, Dr. Warnes continued.

For example, PAH is associated with serotonin transporter-gene polymorphisms and increased circulating serotonin levels, raising the possibility that SSRIs might be beneficial. Potassium channels are downregulated on the pulmonary artery smooth muscle cells of patients with PAH, suggesting a therapeutic role for a potassium channel opener. The disease is also marked by increased circulating cytokines, autoantibodies, and chemokine expression, pointing to a potential application for immunosuppressive agents.

Patients with PAH have reduced vascular levels of vasoactive intestinal peptide; perhaps administration of vasoactive intestinal peptides would provide benefit. PAH is also marked by increased vascular endothelial growth factor activity, which could be addressed by antiangiogenesis agents. And even though warfarin has been standard therapy in PAH for decades, the effect of aspirin has never been studied, Dr. Warnes noted.

INHALED THERAPY DEPOSITS THE DRUG IN WELL-VENTILATED AREAS OF THE LUNG, REDUCING VENTILATION-PERFUSION MISMATCH. Dr. Warnes

SNOWMASS, COLO. — Implantable left atrial pressure sensors may provide a breakthrough in the outpatient management of heart failure by identifying impending acute decompensations hours to days before symptom onset, said Dr. James S. Forrester at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.

“I believe that by using implanted hemodynamic sensors, the mechanisms responsible for acute decompensation of heart failure can be defined in the vast majority of patients, and that the physician can prevent these episodes using preplanned strategies. Implanted sensors will be able to decrease hospitalization, reduce progression of heart failure, and increase quality of life in these patients,” said Dr. Forrester, professor of cardiovascular research at Cedars-Sinai Medical Center and professor of medicine at the University of California, both in Los Angeles.

Heart failure (HF) is “arguably the biggest problem in all of health care,” he said. It already tops the list in terms of Medicare hospitalization costs, a situation that will only worsen with the aging of the population.

Dr. Gregg C. Fonarow of the University of California, Los Angeles, showed in previous research that HF patients with a well-controlled left atrial pressure (LAP) of 16 mm Hg or less at hospital discharge had a 46% lower mortality and 85% reduction in rehospitalizations, compared with those with a higher LAP.

By contrast, cardiac output, right atrial or pulmonary artery pressures, and systemic vascular resistance each failed to predict outcomes.

“Increased left atrial pressure is associated with increased acute and long-term mortality and is the real driver of heart failure rehospitalization,” Dr. Forrester stressed.

There are two investigational implanted devices that are being developed for LAP assessment. The first is the Medtronic Chronicle, which is under review by the Food and Drug Administration for possible marketing approval. Dr. Forrester is involved in studies of a second device, the Savacor HeartPOD System, which was invented by colleagues at Cedars-Sinai.

The HeartPOD consists of a pressure monitor placed in the left atrium via transseptal catheterization and a handheld device that can convey information to the patient.

The device beeps at certain times during the day to remind the patient to record the LAP. It also stores the LAP waveform and gives the patient instructions that have been previously entered into the device by the physician.

The instructions could be about changes in medications and activity in response to different LAP levels, and, if warranted, a directive to contact the physician.

To date, the HeartPOD has been implanted in 18 heart failure patients, with a collective 76 months of follow-up. Although that is insufficient clinical experience from which to draw conclusions, the pilot study results are encouraging.

The number of total hospitalizations was significantly lower, compared with an equal period in the previous year, and there have been no unplanned HF hospitalizations or clinic visits since the monitors were activated, Dr. Forrester said.

The early experience with the HeartPOD has already yielded fascinating new insights into HF physiology. For example, huge fluctuations in LAP occur during the course of a day, most of which are asymptomatic.

But as LAP goes up, increasingly large V-wave peaks appear, which is evidence the patient is developing mitral insufficiency. And when LAP increases to a certain level, a patient often becomes dyspneic. Some patients exhibit diurnal variation in LAP, with the peak coming in the early morning. These LAP variations can be attenuated—and dyspnea often prevented—by preemptive changes in medications, according to Dr. Forrester.

The Medtronic device was assessed in the previously reported 274-patient Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) randomized trial.

In that study, physicians used data from patients' implantable monitors to guide HF therapy.

The patients had a 22% reduction in the primary study end point—the 6-month combined incidence of HF-related hospitalizations and emergency department and urgent-care visits— compared with controls.

However, this finding was not statistically significant, probably because the trial was underpowered, Dr. Forrester said.

But he noted that the Chronicle's sensor, which is placed near the right ventricular outflow tract and infers LAP indirectly from a measurement of pulmonary artery end diastolic pressure, could sometimes give inaccurate LAP results.

Dr. Forrester is chair of the scientific advisory committee for Savacor, a Research!America company. He holds a significant financial interest in the company.

SNOWMASS, COLO. — Implantable left atrial pressure sensors may provide a breakthrough in the outpatient management of heart failure by identifying impending acute decompensations hours to days before symptom onset, said Dr. James S. Forrester at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.

“I believe that by using implanted hemodynamic sensors, the mechanisms responsible for acute decompensation of heart failure can be defined in the vast majority of patients, and that the physician can prevent these episodes using preplanned strategies. Implanted sensors will be able to decrease hospitalization, reduce progression of heart failure, and increase quality of life in these patients,” said Dr. Forrester, professor of cardiovascular research at Cedars-Sinai Medical Center and professor of medicine at the University of California, both in Los Angeles.

Heart failure (HF) is “arguably the biggest problem in all of health care,” he said. It already tops the list in terms of Medicare hospitalization costs, a situation that will only worsen with the aging of the population.

Dr. Gregg C. Fonarow of the University of California, Los Angeles, showed in previous research that HF patients with a well-controlled left atrial pressure (LAP) of 16 mm Hg or less at hospital discharge had a 46% lower mortality and 85% reduction in rehospitalizations, compared with those with a higher LAP.

By contrast, cardiac output, right atrial or pulmonary artery pressures, and systemic vascular resistance each failed to predict outcomes.

“Increased left atrial pressure is associated with increased acute and long-term mortality and is the real driver of heart failure rehospitalization,” Dr. Forrester stressed.

There are two investigational implanted devices that are being developed for LAP assessment. The first is the Medtronic Chronicle, which is under review by the Food and Drug Administration for possible marketing approval. Dr. Forrester is involved in studies of a second device, the Savacor HeartPOD System, which was invented by colleagues at Cedars-Sinai.

The HeartPOD consists of a pressure monitor placed in the left atrium via transseptal catheterization and a handheld device that can convey information to the patient.

The device beeps at certain times during the day to remind the patient to record the LAP. It also stores the LAP waveform and gives the patient instructions that have been previously entered into the device by the physician.

The instructions could be about changes in medications and activity in response to different LAP levels, and, if warranted, a directive to contact the physician.

To date, the HeartPOD has been implanted in 18 heart failure patients, with a collective 76 months of follow-up. Although that is insufficient clinical experience from which to draw conclusions, the pilot study results are encouraging.

The number of total hospitalizations was significantly lower, compared with an equal period in the previous year, and there have been no unplanned HF hospitalizations or clinic visits since the monitors were activated, Dr. Forrester said.

The early experience with the HeartPOD has already yielded fascinating new insights into HF physiology. For example, huge fluctuations in LAP occur during the course of a day, most of which are asymptomatic.

But as LAP goes up, increasingly large V-wave peaks appear, which is evidence the patient is developing mitral insufficiency. And when LAP increases to a certain level, a patient often becomes dyspneic. Some patients exhibit diurnal variation in LAP, with the peak coming in the early morning. These LAP variations can be attenuated—and dyspnea often prevented—by preemptive changes in medications, according to Dr. Forrester.

The Medtronic device was assessed in the previously reported 274-patient Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) randomized trial.

In that study, physicians used data from patients' implantable monitors to guide HF therapy.

The patients had a 22% reduction in the primary study end point—the 6-month combined incidence of HF-related hospitalizations and emergency department and urgent-care visits— compared with controls.

However, this finding was not statistically significant, probably because the trial was underpowered, Dr. Forrester said.

But he noted that the Chronicle's sensor, which is placed near the right ventricular outflow tract and infers LAP indirectly from a measurement of pulmonary artery end diastolic pressure, could sometimes give inaccurate LAP results.

Dr. Forrester is chair of the scientific advisory committee for Savacor, a Research!America company. He holds a significant financial interest in the company.

SNOWMASS, COLO. — Implantable left atrial pressure sensors may provide a breakthrough in the outpatient management of heart failure by identifying impending acute decompensations hours to days before symptom onset, said Dr. James S. Forrester at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.

“I believe that by using implanted hemodynamic sensors, the mechanisms responsible for acute decompensation of heart failure can be defined in the vast majority of patients, and that the physician can prevent these episodes using preplanned strategies. Implanted sensors will be able to decrease hospitalization, reduce progression of heart failure, and increase quality of life in these patients,” said Dr. Forrester, professor of cardiovascular research at Cedars-Sinai Medical Center and professor of medicine at the University of California, both in Los Angeles.

Heart failure (HF) is “arguably the biggest problem in all of health care,” he said. It already tops the list in terms of Medicare hospitalization costs, a situation that will only worsen with the aging of the population.

Dr. Gregg C. Fonarow of the University of California, Los Angeles, showed in previous research that HF patients with a well-controlled left atrial pressure (LAP) of 16 mm Hg or less at hospital discharge had a 46% lower mortality and 85% reduction in rehospitalizations, compared with those with a higher LAP.

By contrast, cardiac output, right atrial or pulmonary artery pressures, and systemic vascular resistance each failed to predict outcomes.

“Increased left atrial pressure is associated with increased acute and long-term mortality and is the real driver of heart failure rehospitalization,” Dr. Forrester stressed.

There are two investigational implanted devices that are being developed for LAP assessment. The first is the Medtronic Chronicle, which is under review by the Food and Drug Administration for possible marketing approval. Dr. Forrester is involved in studies of a second device, the Savacor HeartPOD System, which was invented by colleagues at Cedars-Sinai.

The HeartPOD consists of a pressure monitor placed in the left atrium via transseptal catheterization and a handheld device that can convey information to the patient.

The device beeps at certain times during the day to remind the patient to record the LAP. It also stores the LAP waveform and gives the patient instructions that have been previously entered into the device by the physician.

The instructions could be about changes in medications and activity in response to different LAP levels, and, if warranted, a directive to contact the physician.

To date, the HeartPOD has been implanted in 18 heart failure patients, with a collective 76 months of follow-up. Although that is insufficient clinical experience from which to draw conclusions, the pilot study results are encouraging.

The number of total hospitalizations was significantly lower, compared with an equal period in the previous year, and there have been no unplanned HF hospitalizations or clinic visits since the monitors were activated, Dr. Forrester said.

The early experience with the HeartPOD has already yielded fascinating new insights into HF physiology. For example, huge fluctuations in LAP occur during the course of a day, most of which are asymptomatic.

But as LAP goes up, increasingly large V-wave peaks appear, which is evidence the patient is developing mitral insufficiency. And when LAP increases to a certain level, a patient often becomes dyspneic. Some patients exhibit diurnal variation in LAP, with the peak coming in the early morning. These LAP variations can be attenuated—and dyspnea often prevented—by preemptive changes in medications, according to Dr. Forrester.

The Medtronic device was assessed in the previously reported 274-patient Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) randomized trial.

In that study, physicians used data from patients' implantable monitors to guide HF therapy.

The patients had a 22% reduction in the primary study end point—the 6-month combined incidence of HF-related hospitalizations and emergency department and urgent-care visits— compared with controls.

However, this finding was not statistically significant, probably because the trial was underpowered, Dr. Forrester said.

But he noted that the Chronicle's sensor, which is placed near the right ventricular outflow tract and infers LAP indirectly from a measurement of pulmonary artery end diastolic pressure, could sometimes give inaccurate LAP results.

Dr. Forrester is chair of the scientific advisory committee for Savacor, a Research!America company. He holds a significant financial interest in the company.

SNOWMASS, COLO. — American physicians are probably overtreating many patients with advanced heart failure and conduction delay by implanting combined biventricular pacemaker/cardioverter defibrillators, Dr. Michael R. Gold said at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.

It's likely that in many such patients, a simpler biventricular pacemaker for cardiac resynchronization therapy (CRT) alone would achieve the same goals of reduced mortality, fewer hospitalizations, and improved quality of life, compared with medical management, according to Dr. Gold, professor of medicine and director of adult cardiology at the Medical University of South Carolina in Charleston.

“We do not have definitive data that biventricular pacemaker/defibrillators are better than biventricular pacing alone, despite being about four times the cost,” he said.

Yet 9 out of 10 devices implanted for treatment of advanced heart failure in the United States are combination CRT/implantable cardioverter defibrillators (ICDs), whereas European physicians tend to favor CRT alone, he said.

And a landmark European trial, the Cardiac Resynchronization-Heart Failure (CARE-HF) study—“one of the most important studies ever done in this field,” in Dr. Gold's view—showed that CRT without an ICD resulted in a 45% reduction in death from worsening heart failure and a 46% drop in sudden death over 3 years, compared with medical management, said Dr. Gold.

For now, however, it is not clear which specific patients ought to get a simple biventricular pacemaker rather than a combined CRT/ICD device; that issue is being investigated in the second Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT-2).

In addition to the mortality benefit, cardiac resynchronization therapy brings impressive quality-of-life and economic gains. In the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial, reported in 2002, CRT resulted in a 50-m improvement in 6-minute walk distance after 6 months. No heart failure drug provides an improvement of comparable magnitude.

CRT has been shown in multiple studies to cut hospitalizations by up to 50%, compared with medical management alone. “If you start to play that out, we're not talking about the expense of resynchronization, we're talking about the cost savings,” Dr. Gold said.

“It actually saves money to put in a biventricular pacemaker in the right group of patients because the amount saved in hospitalizations more than offsets the cost of this therapy,” he added.

Cardiac resynchronization therapy is so effective because it has been shown to increase myocardial contractility while reducing myocardial oxygen consumption. The only other treatment that can do that is a β-blocker.

“Biventricular pacing is essentially an electronic β-blocker for our patients. We see virtually the same response long term with β-blockers that we see with CRT,” he explained.

He stressed that cardiac resynchronization therapy needs to be used in conjunction with optimal medical therapy. Indeed, CRT actually facilitates drug therapy. For example, by regulating blood pressure and minimizing hypotension, CRT permits uptitration of ACE inhibitors. And because CRT prevents bradycardia—a common limiting factor in β-blocker therapy—that drug can also be uptitrated.

The CRT nonresponder rate is high—30% in most studies.

It's not widely appreciated that this nonresponder group includes a substantial number of patients who are made hemodynamically worse by biventricular pacing.

“These tend to be patients with a narrower QRS interval. I am often referred patients with a QRS interval of 120, 115, or even 110 milliseconds, with the comment that 'Their heart failure is bad—why don't you put in a biventricular pacemaker?' Well, one of the reasons not to is that you can make these patients worse. They're better off conducting through their native conduction system than to artificially be stimulated from the right ventricular apex or left ventricular free wall,” Dr. Gold said.

“If you look at large patient series using QRS duration as a crude way to try to identify these groups of patients, you'll find that when you get out to 160–170 milliseconds, 80%–90% of patients are going to respond,” he said. But down at 125 milliseconds only about 20% are going to be responders, and a very significant percentage of the others not only will not be responders but will have an adverse hemodynamic response to this therapy,” he added.

Dr. Gold serves as a consultant to the device makers Guidant Corp. and Medtronic Inc.

SNOWMASS, COLO. — American physicians are probably overtreating many patients with advanced heart failure and conduction delay by implanting combined biventricular pacemaker/cardioverter defibrillators, Dr. Michael R. Gold said at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.

It's likely that in many such patients, a simpler biventricular pacemaker for cardiac resynchronization therapy (CRT) alone would achieve the same goals of reduced mortality, fewer hospitalizations, and improved quality of life, compared with medical management, according to Dr. Gold, professor of medicine and director of adult cardiology at the Medical University of South Carolina in Charleston.

“We do not have definitive data that biventricular pacemaker/defibrillators are better than biventricular pacing alone, despite being about four times the cost,” he said.

Yet 9 out of 10 devices implanted for treatment of advanced heart failure in the United States are combination CRT/implantable cardioverter defibrillators (ICDs), whereas European physicians tend to favor CRT alone, he said.

And a landmark European trial, the Cardiac Resynchronization-Heart Failure (CARE-HF) study—“one of the most important studies ever done in this field,” in Dr. Gold's view—showed that CRT without an ICD resulted in a 45% reduction in death from worsening heart failure and a 46% drop in sudden death over 3 years, compared with medical management, said Dr. Gold.

For now, however, it is not clear which specific patients ought to get a simple biventricular pacemaker rather than a combined CRT/ICD device; that issue is being investigated in the second Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT-2).

In addition to the mortality benefit, cardiac resynchronization therapy brings impressive quality-of-life and economic gains. In the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial, reported in 2002, CRT resulted in a 50-m improvement in 6-minute walk distance after 6 months. No heart failure drug provides an improvement of comparable magnitude.

CRT has been shown in multiple studies to cut hospitalizations by up to 50%, compared with medical management alone. “If you start to play that out, we're not talking about the expense of resynchronization, we're talking about the cost savings,” Dr. Gold said.

“It actually saves money to put in a biventricular pacemaker in the right group of patients because the amount saved in hospitalizations more than offsets the cost of this therapy,” he added.

Cardiac resynchronization therapy is so effective because it has been shown to increase myocardial contractility while reducing myocardial oxygen consumption. The only other treatment that can do that is a β-blocker.

“Biventricular pacing is essentially an electronic β-blocker for our patients. We see virtually the same response long term with β-blockers that we see with CRT,” he explained.

He stressed that cardiac resynchronization therapy needs to be used in conjunction with optimal medical therapy. Indeed, CRT actually facilitates drug therapy. For example, by regulating blood pressure and minimizing hypotension, CRT permits uptitration of ACE inhibitors. And because CRT prevents bradycardia—a common limiting factor in β-blocker therapy—that drug can also be uptitrated.

The CRT nonresponder rate is high—30% in most studies.

It's not widely appreciated that this nonresponder group includes a substantial number of patients who are made hemodynamically worse by biventricular pacing.

“These tend to be patients with a narrower QRS interval. I am often referred patients with a QRS interval of 120, 115, or even 110 milliseconds, with the comment that 'Their heart failure is bad—why don't you put in a biventricular pacemaker?' Well, one of the reasons not to is that you can make these patients worse. They're better off conducting through their native conduction system than to artificially be stimulated from the right ventricular apex or left ventricular free wall,” Dr. Gold said.

“If you look at large patient series using QRS duration as a crude way to try to identify these groups of patients, you'll find that when you get out to 160–170 milliseconds, 80%–90% of patients are going to respond,” he said. But down at 125 milliseconds only about 20% are going to be responders, and a very significant percentage of the others not only will not be responders but will have an adverse hemodynamic response to this therapy,” he added.

Dr. Gold serves as a consultant to the device makers Guidant Corp. and Medtronic Inc.

SNOWMASS, COLO. — American physicians are probably overtreating many patients with advanced heart failure and conduction delay by implanting combined biventricular pacemaker/cardioverter defibrillators, Dr. Michael R. Gold said at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.

It's likely that in many such patients, a simpler biventricular pacemaker for cardiac resynchronization therapy (CRT) alone would achieve the same goals of reduced mortality, fewer hospitalizations, and improved quality of life, compared with medical management, according to Dr. Gold, professor of medicine and director of adult cardiology at the Medical University of South Carolina in Charleston.

“We do not have definitive data that biventricular pacemaker/defibrillators are better than biventricular pacing alone, despite being about four times the cost,” he said.

Yet 9 out of 10 devices implanted for treatment of advanced heart failure in the United States are combination CRT/implantable cardioverter defibrillators (ICDs), whereas European physicians tend to favor CRT alone, he said.

And a landmark European trial, the Cardiac Resynchronization-Heart Failure (CARE-HF) study—“one of the most important studies ever done in this field,” in Dr. Gold's view—showed that CRT without an ICD resulted in a 45% reduction in death from worsening heart failure and a 46% drop in sudden death over 3 years, compared with medical management, said Dr. Gold.

For now, however, it is not clear which specific patients ought to get a simple biventricular pacemaker rather than a combined CRT/ICD device; that issue is being investigated in the second Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT-2).

In addition to the mortality benefit, cardiac resynchronization therapy brings impressive quality-of-life and economic gains. In the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial, reported in 2002, CRT resulted in a 50-m improvement in 6-minute walk distance after 6 months. No heart failure drug provides an improvement of comparable magnitude.

CRT has been shown in multiple studies to cut hospitalizations by up to 50%, compared with medical management alone. “If you start to play that out, we're not talking about the expense of resynchronization, we're talking about the cost savings,” Dr. Gold said.

“It actually saves money to put in a biventricular pacemaker in the right group of patients because the amount saved in hospitalizations more than offsets the cost of this therapy,” he added.

Cardiac resynchronization therapy is so effective because it has been shown to increase myocardial contractility while reducing myocardial oxygen consumption. The only other treatment that can do that is a β-blocker.

“Biventricular pacing is essentially an electronic β-blocker for our patients. We see virtually the same response long term with β-blockers that we see with CRT,” he explained.

He stressed that cardiac resynchronization therapy needs to be used in conjunction with optimal medical therapy. Indeed, CRT actually facilitates drug therapy. For example, by regulating blood pressure and minimizing hypotension, CRT permits uptitration of ACE inhibitors. And because CRT prevents bradycardia—a common limiting factor in β-blocker therapy—that drug can also be uptitrated.

The CRT nonresponder rate is high—30% in most studies.

It's not widely appreciated that this nonresponder group includes a substantial number of patients who are made hemodynamically worse by biventricular pacing.

“These tend to be patients with a narrower QRS interval. I am often referred patients with a QRS interval of 120, 115, or even 110 milliseconds, with the comment that 'Their heart failure is bad—why don't you put in a biventricular pacemaker?' Well, one of the reasons not to is that you can make these patients worse. They're better off conducting through their native conduction system than to artificially be stimulated from the right ventricular apex or left ventricular free wall,” Dr. Gold said.

“If you look at large patient series using QRS duration as a crude way to try to identify these groups of patients, you'll find that when you get out to 160–170 milliseconds, 80%–90% of patients are going to respond,” he said. But down at 125 milliseconds only about 20% are going to be responders, and a very significant percentage of the others not only will not be responders but will have an adverse hemodynamic response to this therapy,” he added.

Dr. Gold serves as a consultant to the device makers Guidant Corp. and Medtronic Inc.

KEVIN FOLEY, RESEARCH/DESIGN

KEVIN FOLEY, RESEARCH/DESIGN

KEVIN FOLEY, RESEARCH/DESIGN