Heart Failure

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

DALLAS — An automated system may be able to monitor intracardiac pressures and alert physicians when the pattern suggests impending decompensation, based on a pilot analysis of data collected on 95 acute heart failure events.

The system “continuously scans data and can automatically notify the physician when a patient's pressures change meaningfully,” Dr. Philip B. Adamson said at the annual scientific sessions of the American Heart Association.

The scanning system developed by Dr. Adamson and his associates monitors changes in intracardiac pressures measured by the implanted Chronicle device, which is made by Medtronic Inc. and is under review by the Food and Drug Administration. Dr. Adamson has served as a consultant to Medtronic.

“The key to using this data is to learn the right pressure for each patient,” said Dr. Adamson, director of the Heart Failure Institute at the Oklahoma Heart Hospital in Oklahoma City.

The Chronicle implanted device was tested on 274 patients with advanced heart failure in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial. Intracardiac pressure data collected by the device was used by physicians to guide their management of 134 patients. The collected data were not used in the management of 140 control patients.

Data collected by the device for 56 of the control patients were used in Dr. Adamson's analysis. These 56 patients had a total of 95 episodes of acute decompensation that resulted in either a hospital admission or treatment in an emergency department or urgent-care clinic.

The automated data monitoring focused on the estimated pulmonary-artery diastolic pressure. A rule about changes in this pressure was devised using pressure information gathered before 42 of the 95 events. The pattern was that events usually occurred about 2 weeks after a significant increase in the pulmonary-artery diastolic pressure, said Dr. Adamson. This criterion was able to identify 35 (83%) of the 42 events.

This criterion was then applied on a test basis to the remaining 53 clinical events used in the analysis. A 7-day average of prior pulmonary-artery diastolic pressures was calculated for each patient every day, and this adaptive reference value was applied to each day's new pressure readings.

Small changes in pulmonary-artery pressure over a long period of time, or large changes in pressure over a short period of time were both considered flags of an impending event.

This method identified 43 (81%) of the 53 heart failure events included in the test.

The impending events were flagged an average of 26 days before the events actually occurred.

DALLAS — An automated system may be able to monitor intracardiac pressures and alert physicians when the pattern suggests impending decompensation, based on a pilot analysis of data collected on 95 acute heart failure events.

The system “continuously scans data and can automatically notify the physician when a patient's pressures change meaningfully,” Dr. Philip B. Adamson said at the annual scientific sessions of the American Heart Association.

The scanning system developed by Dr. Adamson and his associates monitors changes in intracardiac pressures measured by the implanted Chronicle device, which is made by Medtronic Inc. and is under review by the Food and Drug Administration. Dr. Adamson has served as a consultant to Medtronic.

“The key to using this data is to learn the right pressure for each patient,” said Dr. Adamson, director of the Heart Failure Institute at the Oklahoma Heart Hospital in Oklahoma City.

The Chronicle implanted device was tested on 274 patients with advanced heart failure in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial. Intracardiac pressure data collected by the device was used by physicians to guide their management of 134 patients. The collected data were not used in the management of 140 control patients.

Data collected by the device for 56 of the control patients were used in Dr. Adamson's analysis. These 56 patients had a total of 95 episodes of acute decompensation that resulted in either a hospital admission or treatment in an emergency department or urgent-care clinic.

The automated data monitoring focused on the estimated pulmonary-artery diastolic pressure. A rule about changes in this pressure was devised using pressure information gathered before 42 of the 95 events. The pattern was that events usually occurred about 2 weeks after a significant increase in the pulmonary-artery diastolic pressure, said Dr. Adamson. This criterion was able to identify 35 (83%) of the 42 events.

This criterion was then applied on a test basis to the remaining 53 clinical events used in the analysis. A 7-day average of prior pulmonary-artery diastolic pressures was calculated for each patient every day, and this adaptive reference value was applied to each day's new pressure readings.

Small changes in pulmonary-artery pressure over a long period of time, or large changes in pressure over a short period of time were both considered flags of an impending event.

This method identified 43 (81%) of the 53 heart failure events included in the test.

The impending events were flagged an average of 26 days before the events actually occurred.

DALLAS — An automated system may be able to monitor intracardiac pressures and alert physicians when the pattern suggests impending decompensation, based on a pilot analysis of data collected on 95 acute heart failure events.

The system “continuously scans data and can automatically notify the physician when a patient's pressures change meaningfully,” Dr. Philip B. Adamson said at the annual scientific sessions of the American Heart Association.

The scanning system developed by Dr. Adamson and his associates monitors changes in intracardiac pressures measured by the implanted Chronicle device, which is made by Medtronic Inc. and is under review by the Food and Drug Administration. Dr. Adamson has served as a consultant to Medtronic.

“The key to using this data is to learn the right pressure for each patient,” said Dr. Adamson, director of the Heart Failure Institute at the Oklahoma Heart Hospital in Oklahoma City.

The Chronicle implanted device was tested on 274 patients with advanced heart failure in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial. Intracardiac pressure data collected by the device was used by physicians to guide their management of 134 patients. The collected data were not used in the management of 140 control patients.

Data collected by the device for 56 of the control patients were used in Dr. Adamson's analysis. These 56 patients had a total of 95 episodes of acute decompensation that resulted in either a hospital admission or treatment in an emergency department or urgent-care clinic.

The automated data monitoring focused on the estimated pulmonary-artery diastolic pressure. A rule about changes in this pressure was devised using pressure information gathered before 42 of the 95 events. The pattern was that events usually occurred about 2 weeks after a significant increase in the pulmonary-artery diastolic pressure, said Dr. Adamson. This criterion was able to identify 35 (83%) of the 42 events.

This criterion was then applied on a test basis to the remaining 53 clinical events used in the analysis. A 7-day average of prior pulmonary-artery diastolic pressures was calculated for each patient every day, and this adaptive reference value was applied to each day's new pressure readings.

Small changes in pulmonary-artery pressure over a long period of time, or large changes in pressure over a short period of time were both considered flags of an impending event.

This method identified 43 (81%) of the 53 heart failure events included in the test.

The impending events were flagged an average of 26 days before the events actually occurred.

DALLAS — Management of heart failure patients with data from an implanted device that continuously monitors hemodynamic pressures led to a 25% reduction in total days spent in the hospital among patients with class III heart failure in a controlled study with more than 200 patients.

“The number of days spent in the hospital for decompensated heart failure is the principal driver of cost for heart failure treatment, and this was significantly decreased,” Dr. William T. Abraham said at the annual scientific sessions of the American Heart Association.

Use of the device in both outpatients and in hospitalized patients with heart failure “may make episodes of decompensation less extreme, and may help get patients out of the hospital more quickly,” said Dr. Abraham, professor and director of the division of cardiovascular medicine at Ohio State University in Columbus.

The finding came from new analyses of data collected in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial, which tested the clinical impact of managing patients with intracardiac pressure data collected by the implanted Chronicle device. The device is made by Medtronic, which submitted an application for licensing to the Food and Drug Administration last August that was still pending in January.

The primary end point of the COMPASS-HF was reported last March at the annual meeting of the American College of Cardiology. Although patient management guided by pressure data obtained by the Chronicle device led to a 22% cut in the rate of heart failure-related hospitalizations and emergency department and urgent-care visits, the drop was not statistically significant. However, several secondary analyses also were positive in favor of the device, including a new set of secondary analyses presented by Dr. Abraham, who is a consultant and investigator for Medtronic and has received honoraria from the company for speaking.

He cautioned that the COMPASS-HF study was not designed to provide definitive answers to these secondary analyses, and therefore the findings must be considered exploratory.

In addition, researchers at Medtronic have revised the results presented by Dr. Abraham based on more comprehensive patient follow-up. The revised data showed that use of data from the Chronicle device cut the number of hospitalized days for heart failure by 20% instead of the 25% difference reported by Dr. Abraham. The 20% reduction is what was reported to the FDA, said Dr. David Israeli, director of marketing and business development for Medtronic in Minneapolis.

In the COMPASS-HF study, a total of 274 patients with advanced-stage heart failure underwent surgery to receive the subcutaneously-implanted, hemodynamic monitoring device. The intracardiac pressure information collected by the device was used by physicians to guide the management of 134 patients for 6 months. The pressure information was withheld from the treating physicians in the control group of 140 patients. All patients in the study also received optimal medical care based on clinical findings. The benefits of applying information collected by the Chronicle device were greatest in the 85% of patients who entered the study with New York Heart Association class III disease. Those with class IV disease had much less benefit.

The reduction in hospitalized days using data collected by the implanted device was more marked if the analysis excluded outlier patients with hospitalizations that extended beyond 30 days. With this exclusion, use of the Chronicle data cut the total number of hospitalized days by 42% for all patients in the study, and by 38% in the class III-only patients.

Another secondary analysis examined the impact of using data from the Chronicle device on the rate of prolonged or short hospitalizations for heart failure. Among the class III-only patients, use of Chronicle information was associated with an average rate of 0.19 long hospitalizations (more than 5 days) every 6 months, compared with a rate of 0.31 long hospitalizations every 6 months in the control group, a 40% decrease in favor of the device. Use of the device also was associated with a 0.28 rate of short hospitalizations (5 days or less) every 6 months, compared with a rate of 0.42 short hospitalizations every 6 months in the control group.

Despite the lack of a statistically significant positive result for the primary end point of the COMPASS-HF trial, the researchers who ran the study believe that the results demonstrate the device's efficacy.

“It's a positive study overall,” commented Dr. Robert C. Bourge, lead investigator for the study and professor and director of the division of cardiovascular disease at the University of Alabama, Birmingham.

But other experts are concerned about paying for this intensive approach to patient management.

“The implications are profound regarding the cost of care,” commented Dr. Harlan M. Krumholz, professor of medicine and epidemiology at Yale University, New Haven, Conn. “How should we decide which patients should get this?”

“We're developing models of how to use it,” said Dr. Bourge, who acknowledged that not all physicians would have the expertise or time to review so many pressure measurements for their patients.

Because of this, researchers are working on developing an automated way to review the large number of intracardiac pressure measurements that are made in each patient.

DALLAS — Management of heart failure patients with data from an implanted device that continuously monitors hemodynamic pressures led to a 25% reduction in total days spent in the hospital among patients with class III heart failure in a controlled study with more than 200 patients.

“The number of days spent in the hospital for decompensated heart failure is the principal driver of cost for heart failure treatment, and this was significantly decreased,” Dr. William T. Abraham said at the annual scientific sessions of the American Heart Association.

Use of the device in both outpatients and in hospitalized patients with heart failure “may make episodes of decompensation less extreme, and may help get patients out of the hospital more quickly,” said Dr. Abraham, professor and director of the division of cardiovascular medicine at Ohio State University in Columbus.

The finding came from new analyses of data collected in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial, which tested the clinical impact of managing patients with intracardiac pressure data collected by the implanted Chronicle device. The device is made by Medtronic, which submitted an application for licensing to the Food and Drug Administration last August that was still pending in January.

The primary end point of the COMPASS-HF was reported last March at the annual meeting of the American College of Cardiology. Although patient management guided by pressure data obtained by the Chronicle device led to a 22% cut in the rate of heart failure-related hospitalizations and emergency department and urgent-care visits, the drop was not statistically significant. However, several secondary analyses also were positive in favor of the device, including a new set of secondary analyses presented by Dr. Abraham, who is a consultant and investigator for Medtronic and has received honoraria from the company for speaking.

He cautioned that the COMPASS-HF study was not designed to provide definitive answers to these secondary analyses, and therefore the findings must be considered exploratory.

In addition, researchers at Medtronic have revised the results presented by Dr. Abraham based on more comprehensive patient follow-up. The revised data showed that use of data from the Chronicle device cut the number of hospitalized days for heart failure by 20% instead of the 25% difference reported by Dr. Abraham. The 20% reduction is what was reported to the FDA, said Dr. David Israeli, director of marketing and business development for Medtronic in Minneapolis.

In the COMPASS-HF study, a total of 274 patients with advanced-stage heart failure underwent surgery to receive the subcutaneously-implanted, hemodynamic monitoring device. The intracardiac pressure information collected by the device was used by physicians to guide the management of 134 patients for 6 months. The pressure information was withheld from the treating physicians in the control group of 140 patients. All patients in the study also received optimal medical care based on clinical findings. The benefits of applying information collected by the Chronicle device were greatest in the 85% of patients who entered the study with New York Heart Association class III disease. Those with class IV disease had much less benefit.

The reduction in hospitalized days using data collected by the implanted device was more marked if the analysis excluded outlier patients with hospitalizations that extended beyond 30 days. With this exclusion, use of the Chronicle data cut the total number of hospitalized days by 42% for all patients in the study, and by 38% in the class III-only patients.

Another secondary analysis examined the impact of using data from the Chronicle device on the rate of prolonged or short hospitalizations for heart failure. Among the class III-only patients, use of Chronicle information was associated with an average rate of 0.19 long hospitalizations (more than 5 days) every 6 months, compared with a rate of 0.31 long hospitalizations every 6 months in the control group, a 40% decrease in favor of the device. Use of the device also was associated with a 0.28 rate of short hospitalizations (5 days or less) every 6 months, compared with a rate of 0.42 short hospitalizations every 6 months in the control group.

Despite the lack of a statistically significant positive result for the primary end point of the COMPASS-HF trial, the researchers who ran the study believe that the results demonstrate the device's efficacy.

“It's a positive study overall,” commented Dr. Robert C. Bourge, lead investigator for the study and professor and director of the division of cardiovascular disease at the University of Alabama, Birmingham.

But other experts are concerned about paying for this intensive approach to patient management.

“The implications are profound regarding the cost of care,” commented Dr. Harlan M. Krumholz, professor of medicine and epidemiology at Yale University, New Haven, Conn. “How should we decide which patients should get this?”

“We're developing models of how to use it,” said Dr. Bourge, who acknowledged that not all physicians would have the expertise or time to review so many pressure measurements for their patients.

Because of this, researchers are working on developing an automated way to review the large number of intracardiac pressure measurements that are made in each patient.

DALLAS — Management of heart failure patients with data from an implanted device that continuously monitors hemodynamic pressures led to a 25% reduction in total days spent in the hospital among patients with class III heart failure in a controlled study with more than 200 patients.

“The number of days spent in the hospital for decompensated heart failure is the principal driver of cost for heart failure treatment, and this was significantly decreased,” Dr. William T. Abraham said at the annual scientific sessions of the American Heart Association.

Use of the device in both outpatients and in hospitalized patients with heart failure “may make episodes of decompensation less extreme, and may help get patients out of the hospital more quickly,” said Dr. Abraham, professor and director of the division of cardiovascular medicine at Ohio State University in Columbus.

The finding came from new analyses of data collected in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure (COMPASS-HF) trial, which tested the clinical impact of managing patients with intracardiac pressure data collected by the implanted Chronicle device. The device is made by Medtronic, which submitted an application for licensing to the Food and Drug Administration last August that was still pending in January.

The primary end point of the COMPASS-HF was reported last March at the annual meeting of the American College of Cardiology. Although patient management guided by pressure data obtained by the Chronicle device led to a 22% cut in the rate of heart failure-related hospitalizations and emergency department and urgent-care visits, the drop was not statistically significant. However, several secondary analyses also were positive in favor of the device, including a new set of secondary analyses presented by Dr. Abraham, who is a consultant and investigator for Medtronic and has received honoraria from the company for speaking.

He cautioned that the COMPASS-HF study was not designed to provide definitive answers to these secondary analyses, and therefore the findings must be considered exploratory.

In addition, researchers at Medtronic have revised the results presented by Dr. Abraham based on more comprehensive patient follow-up. The revised data showed that use of data from the Chronicle device cut the number of hospitalized days for heart failure by 20% instead of the 25% difference reported by Dr. Abraham. The 20% reduction is what was reported to the FDA, said Dr. David Israeli, director of marketing and business development for Medtronic in Minneapolis.

In the COMPASS-HF study, a total of 274 patients with advanced-stage heart failure underwent surgery to receive the subcutaneously-implanted, hemodynamic monitoring device. The intracardiac pressure information collected by the device was used by physicians to guide the management of 134 patients for 6 months. The pressure information was withheld from the treating physicians in the control group of 140 patients. All patients in the study also received optimal medical care based on clinical findings. The benefits of applying information collected by the Chronicle device were greatest in the 85% of patients who entered the study with New York Heart Association class III disease. Those with class IV disease had much less benefit.

The reduction in hospitalized days using data collected by the implanted device was more marked if the analysis excluded outlier patients with hospitalizations that extended beyond 30 days. With this exclusion, use of the Chronicle data cut the total number of hospitalized days by 42% for all patients in the study, and by 38% in the class III-only patients.

Another secondary analysis examined the impact of using data from the Chronicle device on the rate of prolonged or short hospitalizations for heart failure. Among the class III-only patients, use of Chronicle information was associated with an average rate of 0.19 long hospitalizations (more than 5 days) every 6 months, compared with a rate of 0.31 long hospitalizations every 6 months in the control group, a 40% decrease in favor of the device. Use of the device also was associated with a 0.28 rate of short hospitalizations (5 days or less) every 6 months, compared with a rate of 0.42 short hospitalizations every 6 months in the control group.

Despite the lack of a statistically significant positive result for the primary end point of the COMPASS-HF trial, the researchers who ran the study believe that the results demonstrate the device's efficacy.

“It's a positive study overall,” commented Dr. Robert C. Bourge, lead investigator for the study and professor and director of the division of cardiovascular disease at the University of Alabama, Birmingham.

But other experts are concerned about paying for this intensive approach to patient management.

“The implications are profound regarding the cost of care,” commented Dr. Harlan M. Krumholz, professor of medicine and epidemiology at Yale University, New Haven, Conn. “How should we decide which patients should get this?”

“We're developing models of how to use it,” said Dr. Bourge, who acknowledged that not all physicians would have the expertise or time to review so many pressure measurements for their patients.

Because of this, researchers are working on developing an automated way to review the large number of intracardiac pressure measurements that are made in each patient.

BOCA RATON, FLA. — When it comes to treatment options, palliative care, and decision making for patients with end-stage heart failure, cardiologists, internists, family physicians, and geriatricians are similarly lacking in awareness, according to a national pilot survey.

The American College of Cardiology and the American Heart Association's recommendations for the care of heart failure patients include a call for cardiologists to counsel patients about end-of-life issues.

However, most of the care of heart failure patients is done by noncardiologist physicians, and there is still uncertainty about which physicians should address end-of-life concerns with end-stage heart failure patients.

“The question is, who is going to have 'the talk'?” Dr. Paul J. Hauptman said in an interview.

“More and more patients have heart failure, and more and more patients are going to die from heart failure. What are we going to do with this burgeoning population of patients with heart failure?” asked Dr. Hauptman, professor of medicine, division of cardiology, and director of heart failure/transplantation at St. Louis (Mo.) University.

In an attempt to answer that question, Dr. Hauptman and his associates surveyed cardiologists, family physicians, internists, and geriatricians about the management of patients with end-stage heart failure. The investigators randomly selected physicians from the American Medical Association Master File.

The administration of the 51-question survey is ongoing, with the goal of garnering opinions from 1,450 physicians. Preliminary results from 76 responses were given in a poster presentation at the annual meeting of the Heart Failure Society of America.

The survey indicates a similar lack of awareness about published guidelines for heart failure (44% of cardiologists, 47% of noncardiologists), a similar belief in left-ventricular pacing as a life-extending measure (44% of cardiologists, 41% of noncardiologists), and a similar level of uncertainty about when to refer a patient to hospice care (52% of cardiologists, 53% of noncardiologists).

Almost 85% of the noncardiologists who responded to the survey said they believed that they, and not cardiologists, should initiate end-of-life discussions with their patients. “The noncardiologists really thought they were better [at that] than the cardiologists,” Dr. Hauptman commented.

However, he added, most of the generalists reported that they had never had such a discussion with a patient or a patient's family.

“Cardiologists have an acute-care perspective. We don't really know about what is going on at the end of life,” Dr. Hauptman said. “It's going to take education and discussions at national meetings [to understand that].”

The majority of respondents (91% of cardiologists, 67% of noncardiologists) do not use standard quality of life measurements for patients with end-stage heart failure.

“This would be kind of shocking” if confirmed by the full survey, he said.

Most of the cardiologists who were surveyed (65%) said that they have discussed implantable cardioverter defibrillator deactivation with an end-stage patient or family member, compared with 35% of noncardiologists.

With the increasing prevalence of heart failure, Dr. Hauptman asserted, “more patients are going to show up with a device. Do you turn them off or [do you] not turn them off?”

Dr. Hauptman said that he hoped the final results of the survey would provide even more insight about physicians' attitudes toward end-stage heart failure and that the information will be able to be used to design effective interventions in the future.

BOCA RATON, FLA. — When it comes to treatment options, palliative care, and decision making for patients with end-stage heart failure, cardiologists, internists, family physicians, and geriatricians are similarly lacking in awareness, according to a national pilot survey.

The American College of Cardiology and the American Heart Association's recommendations for the care of heart failure patients include a call for cardiologists to counsel patients about end-of-life issues.

However, most of the care of heart failure patients is done by noncardiologist physicians, and there is still uncertainty about which physicians should address end-of-life concerns with end-stage heart failure patients.

“The question is, who is going to have 'the talk'?” Dr. Paul J. Hauptman said in an interview.

“More and more patients have heart failure, and more and more patients are going to die from heart failure. What are we going to do with this burgeoning population of patients with heart failure?” asked Dr. Hauptman, professor of medicine, division of cardiology, and director of heart failure/transplantation at St. Louis (Mo.) University.

In an attempt to answer that question, Dr. Hauptman and his associates surveyed cardiologists, family physicians, internists, and geriatricians about the management of patients with end-stage heart failure. The investigators randomly selected physicians from the American Medical Association Master File.

The administration of the 51-question survey is ongoing, with the goal of garnering opinions from 1,450 physicians. Preliminary results from 76 responses were given in a poster presentation at the annual meeting of the Heart Failure Society of America.

The survey indicates a similar lack of awareness about published guidelines for heart failure (44% of cardiologists, 47% of noncardiologists), a similar belief in left-ventricular pacing as a life-extending measure (44% of cardiologists, 41% of noncardiologists), and a similar level of uncertainty about when to refer a patient to hospice care (52% of cardiologists, 53% of noncardiologists).

Almost 85% of the noncardiologists who responded to the survey said they believed that they, and not cardiologists, should initiate end-of-life discussions with their patients. “The noncardiologists really thought they were better [at that] than the cardiologists,” Dr. Hauptman commented.

However, he added, most of the generalists reported that they had never had such a discussion with a patient or a patient's family.

“Cardiologists have an acute-care perspective. We don't really know about what is going on at the end of life,” Dr. Hauptman said. “It's going to take education and discussions at national meetings [to understand that].”

The majority of respondents (91% of cardiologists, 67% of noncardiologists) do not use standard quality of life measurements for patients with end-stage heart failure.

“This would be kind of shocking” if confirmed by the full survey, he said.

Most of the cardiologists who were surveyed (65%) said that they have discussed implantable cardioverter defibrillator deactivation with an end-stage patient or family member, compared with 35% of noncardiologists.

With the increasing prevalence of heart failure, Dr. Hauptman asserted, “more patients are going to show up with a device. Do you turn them off or [do you] not turn them off?”

Dr. Hauptman said that he hoped the final results of the survey would provide even more insight about physicians' attitudes toward end-stage heart failure and that the information will be able to be used to design effective interventions in the future.

BOCA RATON, FLA. — When it comes to treatment options, palliative care, and decision making for patients with end-stage heart failure, cardiologists, internists, family physicians, and geriatricians are similarly lacking in awareness, according to a national pilot survey.

The American College of Cardiology and the American Heart Association's recommendations for the care of heart failure patients include a call for cardiologists to counsel patients about end-of-life issues.

However, most of the care of heart failure patients is done by noncardiologist physicians, and there is still uncertainty about which physicians should address end-of-life concerns with end-stage heart failure patients.

“The question is, who is going to have 'the talk'?” Dr. Paul J. Hauptman said in an interview.

“More and more patients have heart failure, and more and more patients are going to die from heart failure. What are we going to do with this burgeoning population of patients with heart failure?” asked Dr. Hauptman, professor of medicine, division of cardiology, and director of heart failure/transplantation at St. Louis (Mo.) University.

In an attempt to answer that question, Dr. Hauptman and his associates surveyed cardiologists, family physicians, internists, and geriatricians about the management of patients with end-stage heart failure. The investigators randomly selected physicians from the American Medical Association Master File.

The administration of the 51-question survey is ongoing, with the goal of garnering opinions from 1,450 physicians. Preliminary results from 76 responses were given in a poster presentation at the annual meeting of the Heart Failure Society of America.

The survey indicates a similar lack of awareness about published guidelines for heart failure (44% of cardiologists, 47% of noncardiologists), a similar belief in left-ventricular pacing as a life-extending measure (44% of cardiologists, 41% of noncardiologists), and a similar level of uncertainty about when to refer a patient to hospice care (52% of cardiologists, 53% of noncardiologists).

Almost 85% of the noncardiologists who responded to the survey said they believed that they, and not cardiologists, should initiate end-of-life discussions with their patients. “The noncardiologists really thought they were better [at that] than the cardiologists,” Dr. Hauptman commented.

However, he added, most of the generalists reported that they had never had such a discussion with a patient or a patient's family.

“Cardiologists have an acute-care perspective. We don't really know about what is going on at the end of life,” Dr. Hauptman said. “It's going to take education and discussions at national meetings [to understand that].”

The majority of respondents (91% of cardiologists, 67% of noncardiologists) do not use standard quality of life measurements for patients with end-stage heart failure.

“This would be kind of shocking” if confirmed by the full survey, he said.

Most of the cardiologists who were surveyed (65%) said that they have discussed implantable cardioverter defibrillator deactivation with an end-stage patient or family member, compared with 35% of noncardiologists.

With the increasing prevalence of heart failure, Dr. Hauptman asserted, “more patients are going to show up with a device. Do you turn them off or [do you] not turn them off?”

Dr. Hauptman said that he hoped the final results of the survey would provide even more insight about physicians' attitudes toward end-stage heart failure and that the information will be able to be used to design effective interventions in the future.