Heart Failure

CHICAGO — Despite the underrepresentation of Hispanics in heart failure trials, evidence has emerged suggesting that they have unique risk factors and outcomes that must be taken into clinical consideration.

The evidence also underscores the need to recognize the vast heterogeneity of Hispanics, Dr. Ileana Piña said at a meeting sponsored by the International Society on Hypertension in Blacks.

“Hispanics represent a cultural group, not a racially identifiable group,” said the Cuban-born cardiologist. “You can't lump them all together.”

But that's exactly what has happened. It wasn't until the 2000 U.S. census that the term “Hispanic” was changed to “Spanish, Hispanic, or Latino” to describe persons of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race.

Several studies have made the observation—coined the “Hispanic paradox”—that Hispanics have lower all-cause and cardiovascular mortality, despite increased obesity and diabetes, and lower socioeconomic status, said Dr. Piña, professor of medicine at Case Western Reserve University, Cleveland.

A study of Medicare enrollees found that Hispanics were 1.2 times more likely to be hospitalized for heart failure than were whites, while blacks were 1.5 times more likely. But after adjustment for sex and age, in-hospital mortality was significantly lower in Hispanics and blacks than in whites. A California study also showed that blacks and “Latinos” initially hospitalized with heart failure in 1991 or 1992 were more likely to be rehospitalized than were Asians and whites, but were less likely to die during the following year.

Sociocultural factors are often used to explain the Hispanic paradox, but more recent data are causing some to rethink the paradox or at least to differentiate Hispanics by birthplace. Among diabetics in the San Antonio Heart Study, age- and sex-adjusted hazard ratios indicated that U.S.-born Mexican-Americans have a 66% greater risk of all-cause and CV mortality, compared with non-Hispanic whites, while Mexico-born Mexican-Americans appeared to be at similar risk.

Greater representation in patient registries, research studies, and clinical trials is needed Dr. Piña said. Only one major heart failure trial, HF-ACTION, has specifically differentiated Hispanics, and those patients made up just 3%.

Greater elucidation of heart failure risk factors and outcomes in Hispanic populations could lead to more targeted therapies and risk modification. With one in three U.S. residents expected to be Hispanic by 2050, there is great urgency to act, said Dr. Piña, who disclosed serving as a speaker for AstraZeneca, Novartis, and Merck.

CHICAGO — Despite the underrepresentation of Hispanics in heart failure trials, evidence has emerged suggesting that they have unique risk factors and outcomes that must be taken into clinical consideration.

The evidence also underscores the need to recognize the vast heterogeneity of Hispanics, Dr. Ileana Piña said at a meeting sponsored by the International Society on Hypertension in Blacks.

“Hispanics represent a cultural group, not a racially identifiable group,” said the Cuban-born cardiologist. “You can't lump them all together.”

But that's exactly what has happened. It wasn't until the 2000 U.S. census that the term “Hispanic” was changed to “Spanish, Hispanic, or Latino” to describe persons of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race.

Several studies have made the observation—coined the “Hispanic paradox”—that Hispanics have lower all-cause and cardiovascular mortality, despite increased obesity and diabetes, and lower socioeconomic status, said Dr. Piña, professor of medicine at Case Western Reserve University, Cleveland.

A study of Medicare enrollees found that Hispanics were 1.2 times more likely to be hospitalized for heart failure than were whites, while blacks were 1.5 times more likely. But after adjustment for sex and age, in-hospital mortality was significantly lower in Hispanics and blacks than in whites. A California study also showed that blacks and “Latinos” initially hospitalized with heart failure in 1991 or 1992 were more likely to be rehospitalized than were Asians and whites, but were less likely to die during the following year.

Sociocultural factors are often used to explain the Hispanic paradox, but more recent data are causing some to rethink the paradox or at least to differentiate Hispanics by birthplace. Among diabetics in the San Antonio Heart Study, age- and sex-adjusted hazard ratios indicated that U.S.-born Mexican-Americans have a 66% greater risk of all-cause and CV mortality, compared with non-Hispanic whites, while Mexico-born Mexican-Americans appeared to be at similar risk.

Greater representation in patient registries, research studies, and clinical trials is needed Dr. Piña said. Only one major heart failure trial, HF-ACTION, has specifically differentiated Hispanics, and those patients made up just 3%.

Greater elucidation of heart failure risk factors and outcomes in Hispanic populations could lead to more targeted therapies and risk modification. With one in three U.S. residents expected to be Hispanic by 2050, there is great urgency to act, said Dr. Piña, who disclosed serving as a speaker for AstraZeneca, Novartis, and Merck.

CHICAGO — Despite the underrepresentation of Hispanics in heart failure trials, evidence has emerged suggesting that they have unique risk factors and outcomes that must be taken into clinical consideration.

The evidence also underscores the need to recognize the vast heterogeneity of Hispanics, Dr. Ileana Piña said at a meeting sponsored by the International Society on Hypertension in Blacks.

“Hispanics represent a cultural group, not a racially identifiable group,” said the Cuban-born cardiologist. “You can't lump them all together.”

But that's exactly what has happened. It wasn't until the 2000 U.S. census that the term “Hispanic” was changed to “Spanish, Hispanic, or Latino” to describe persons of Cuban, Mexican, Puerto Rican, South or Central American, or other Spanish culture or origin, regardless of race.

Several studies have made the observation—coined the “Hispanic paradox”—that Hispanics have lower all-cause and cardiovascular mortality, despite increased obesity and diabetes, and lower socioeconomic status, said Dr. Piña, professor of medicine at Case Western Reserve University, Cleveland.

A study of Medicare enrollees found that Hispanics were 1.2 times more likely to be hospitalized for heart failure than were whites, while blacks were 1.5 times more likely. But after adjustment for sex and age, in-hospital mortality was significantly lower in Hispanics and blacks than in whites. A California study also showed that blacks and “Latinos” initially hospitalized with heart failure in 1991 or 1992 were more likely to be rehospitalized than were Asians and whites, but were less likely to die during the following year.

Sociocultural factors are often used to explain the Hispanic paradox, but more recent data are causing some to rethink the paradox or at least to differentiate Hispanics by birthplace. Among diabetics in the San Antonio Heart Study, age- and sex-adjusted hazard ratios indicated that U.S.-born Mexican-Americans have a 66% greater risk of all-cause and CV mortality, compared with non-Hispanic whites, while Mexico-born Mexican-Americans appeared to be at similar risk.

Greater representation in patient registries, research studies, and clinical trials is needed Dr. Piña said. Only one major heart failure trial, HF-ACTION, has specifically differentiated Hispanics, and those patients made up just 3%.

Greater elucidation of heart failure risk factors and outcomes in Hispanic populations could lead to more targeted therapies and risk modification. With one in three U.S. residents expected to be Hispanic by 2050, there is great urgency to act, said Dr. Piña, who disclosed serving as a speaker for AstraZeneca, Novartis, and Merck.

BARCELONA — Erythropoietin therapy in patients with anemia of heart failure resulted in improved exercise capacity, reduced heart failure symptoms, and decreased hospitalizations, and showed strong trends for reduced rates of MI and all-cause mortality in a meta-analysis of 11 small randomized clinical trials.

Moreover, erythropoietin was not associated with an increased rate of adverse events, as in some clinical trials carried out in the settings of cancer or chronic kidney disease. It may be that erythropoietin's angiogenesis-promoting effect is therapeutic in the context of heart failure but is the source of side effects in patients with cancer or renal disease, Dr. Dipak Kotecha said at the annual congress of the European Society of Cardiology.

He was quick to offer a caveat, however: “This is all based on a relatively small sample size. Some of these trials were small proof-of-concept trials, others were mechanistic and looked at the effects of different doses. None were individually powered for clinical events. The follow-up was relatively short, at 2–12 months.”

The 11 randomized trials involved 794 patients with mild to moderate anemia and left ventricular systolic heart failure. Nine of the trials were placebo controlled. Mean baseline hemoglobin was 10.1–11.8 g/dL and rose by 2.0 g/dL in response to erythropoietin therapy.

This 2.0-g/dL increase in hemoglobin was associated with a mean 69-meter improvement in 6-minute walk distance compared with controls, a 96-second increase in exercise duration, and an improvement in New York Heart Association functional class equivalent to three-quarters of a class.

“All of these changes were clinically as well as statistically highly significant,” observed Dr. Kotecha of Royal Brompton Hospital, London.

Peak oxygen consumption, or VO₂ max, increased by an average of 2.3 mL/kg per min. Left ventricular ejection fraction increased in erythropoietin-treated patients by an absolute 5.8% compared with controls; that is comparable to the improvement seen in the major clinical trials of beta-blockers. Quality of life scores using the standard Minnesota and Kansas City instruments showed significant gains as well.

Heart failure hospitalizations in erythropoietin-treated patients were significantly reduced by 36% compared with controls, reflecting an absolute 8% rate difference. “The absolute 8% decrease in hospitalizations for heart failure is very similar to what's been seen in the major clinical trials of beta-blocker therapy in heart failure,” Dr. Kotecha said.

B-type natriuretic peptide levels fell by an average of 40%, or 237 pg/dL, in response to erythropoietin. Again, that is a magnitude of effect similar to what has been seen in clinical trials of combined beta-blocker and ACE inhibitor or angiotensin receptor blocker therapy, he continued.

The risk of all-cause mortality was reduced by 39% in the erythropoietin treatment group, a strong trend that just missed statistical significance. The 27% relative risk reduction in acute MI also was not quite significant. Definitive answers as to whether erythropoietin therapy has a beneficial effect on these key outcomes are anticipated from the ongoing Amgen-sponsored phase III Reduction of Events With Darbepoetin Alfa in Heart Failure (RED-HF) trial, which is randomizing more than 3,000 patients.

Anemia occurs in one-third to one-half of patients with heart failure and has been associated with a markedly worse prognosis. Dr. Kotecha cited as an example a Dutch meta-analysis involving more than 153,000 heart failure patients, 37% of whom were anemic. The mortality after a minimum of 6 months of follow-up was 30% in nonanemic patients and 47% among those with anemia (J. Am. Coll. Cardiol. 2008;52:818–27)

Dr. Kotecha reported having no financial conflicts of interest in connection with the meta-analysis, which was conducted using Cochrane Collaboration methodology and has been submitted to the Cochrane Review for possible publication.

Heart failure hospitalizations in erythropoietin-treated patients were significantly reduced by 36%.

Source DR. KOTECHA

BARCELONA — Erythropoietin therapy in patients with anemia of heart failure resulted in improved exercise capacity, reduced heart failure symptoms, and decreased hospitalizations, and showed strong trends for reduced rates of MI and all-cause mortality in a meta-analysis of 11 small randomized clinical trials.

Moreover, erythropoietin was not associated with an increased rate of adverse events, as in some clinical trials carried out in the settings of cancer or chronic kidney disease. It may be that erythropoietin's angiogenesis-promoting effect is therapeutic in the context of heart failure but is the source of side effects in patients with cancer or renal disease, Dr. Dipak Kotecha said at the annual congress of the European Society of Cardiology.

He was quick to offer a caveat, however: “This is all based on a relatively small sample size. Some of these trials were small proof-of-concept trials, others were mechanistic and looked at the effects of different doses. None were individually powered for clinical events. The follow-up was relatively short, at 2–12 months.”

The 11 randomized trials involved 794 patients with mild to moderate anemia and left ventricular systolic heart failure. Nine of the trials were placebo controlled. Mean baseline hemoglobin was 10.1–11.8 g/dL and rose by 2.0 g/dL in response to erythropoietin therapy.

This 2.0-g/dL increase in hemoglobin was associated with a mean 69-meter improvement in 6-minute walk distance compared with controls, a 96-second increase in exercise duration, and an improvement in New York Heart Association functional class equivalent to three-quarters of a class.

“All of these changes were clinically as well as statistically highly significant,” observed Dr. Kotecha of Royal Brompton Hospital, London.

Peak oxygen consumption, or VO₂ max, increased by an average of 2.3 mL/kg per min. Left ventricular ejection fraction increased in erythropoietin-treated patients by an absolute 5.8% compared with controls; that is comparable to the improvement seen in the major clinical trials of beta-blockers. Quality of life scores using the standard Minnesota and Kansas City instruments showed significant gains as well.

Heart failure hospitalizations in erythropoietin-treated patients were significantly reduced by 36% compared with controls, reflecting an absolute 8% rate difference. “The absolute 8% decrease in hospitalizations for heart failure is very similar to what's been seen in the major clinical trials of beta-blocker therapy in heart failure,” Dr. Kotecha said.

B-type natriuretic peptide levels fell by an average of 40%, or 237 pg/dL, in response to erythropoietin. Again, that is a magnitude of effect similar to what has been seen in clinical trials of combined beta-blocker and ACE inhibitor or angiotensin receptor blocker therapy, he continued.

The risk of all-cause mortality was reduced by 39% in the erythropoietin treatment group, a strong trend that just missed statistical significance. The 27% relative risk reduction in acute MI also was not quite significant. Definitive answers as to whether erythropoietin therapy has a beneficial effect on these key outcomes are anticipated from the ongoing Amgen-sponsored phase III Reduction of Events With Darbepoetin Alfa in Heart Failure (RED-HF) trial, which is randomizing more than 3,000 patients.

Anemia occurs in one-third to one-half of patients with heart failure and has been associated with a markedly worse prognosis. Dr. Kotecha cited as an example a Dutch meta-analysis involving more than 153,000 heart failure patients, 37% of whom were anemic. The mortality after a minimum of 6 months of follow-up was 30% in nonanemic patients and 47% among those with anemia (J. Am. Coll. Cardiol. 2008;52:818–27)

Dr. Kotecha reported having no financial conflicts of interest in connection with the meta-analysis, which was conducted using Cochrane Collaboration methodology and has been submitted to the Cochrane Review for possible publication.

Heart failure hospitalizations in erythropoietin-treated patients were significantly reduced by 36%.

Source DR. KOTECHA

BARCELONA — Erythropoietin therapy in patients with anemia of heart failure resulted in improved exercise capacity, reduced heart failure symptoms, and decreased hospitalizations, and showed strong trends for reduced rates of MI and all-cause mortality in a meta-analysis of 11 small randomized clinical trials.

Moreover, erythropoietin was not associated with an increased rate of adverse events, as in some clinical trials carried out in the settings of cancer or chronic kidney disease. It may be that erythropoietin's angiogenesis-promoting effect is therapeutic in the context of heart failure but is the source of side effects in patients with cancer or renal disease, Dr. Dipak Kotecha said at the annual congress of the European Society of Cardiology.

He was quick to offer a caveat, however: “This is all based on a relatively small sample size. Some of these trials were small proof-of-concept trials, others were mechanistic and looked at the effects of different doses. None were individually powered for clinical events. The follow-up was relatively short, at 2–12 months.”

The 11 randomized trials involved 794 patients with mild to moderate anemia and left ventricular systolic heart failure. Nine of the trials were placebo controlled. Mean baseline hemoglobin was 10.1–11.8 g/dL and rose by 2.0 g/dL in response to erythropoietin therapy.

This 2.0-g/dL increase in hemoglobin was associated with a mean 69-meter improvement in 6-minute walk distance compared with controls, a 96-second increase in exercise duration, and an improvement in New York Heart Association functional class equivalent to three-quarters of a class.

“All of these changes were clinically as well as statistically highly significant,” observed Dr. Kotecha of Royal Brompton Hospital, London.

Peak oxygen consumption, or VO₂ max, increased by an average of 2.3 mL/kg per min. Left ventricular ejection fraction increased in erythropoietin-treated patients by an absolute 5.8% compared with controls; that is comparable to the improvement seen in the major clinical trials of beta-blockers. Quality of life scores using the standard Minnesota and Kansas City instruments showed significant gains as well.

Heart failure hospitalizations in erythropoietin-treated patients were significantly reduced by 36% compared with controls, reflecting an absolute 8% rate difference. “The absolute 8% decrease in hospitalizations for heart failure is very similar to what's been seen in the major clinical trials of beta-blocker therapy in heart failure,” Dr. Kotecha said.

B-type natriuretic peptide levels fell by an average of 40%, or 237 pg/dL, in response to erythropoietin. Again, that is a magnitude of effect similar to what has been seen in clinical trials of combined beta-blocker and ACE inhibitor or angiotensin receptor blocker therapy, he continued.

The risk of all-cause mortality was reduced by 39% in the erythropoietin treatment group, a strong trend that just missed statistical significance. The 27% relative risk reduction in acute MI also was not quite significant. Definitive answers as to whether erythropoietin therapy has a beneficial effect on these key outcomes are anticipated from the ongoing Amgen-sponsored phase III Reduction of Events With Darbepoetin Alfa in Heart Failure (RED-HF) trial, which is randomizing more than 3,000 patients.

Anemia occurs in one-third to one-half of patients with heart failure and has been associated with a markedly worse prognosis. Dr. Kotecha cited as an example a Dutch meta-analysis involving more than 153,000 heart failure patients, 37% of whom were anemic. The mortality after a minimum of 6 months of follow-up was 30% in nonanemic patients and 47% among those with anemia (J. Am. Coll. Cardiol. 2008;52:818–27)

Dr. Kotecha reported having no financial conflicts of interest in connection with the meta-analysis, which was conducted using Cochrane Collaboration methodology and has been submitted to the Cochrane Review for possible publication.

Heart failure hospitalizations in erythropoietin-treated patients were significantly reduced by 36%.

Source DR. KOTECHA

BARCELONA — In its pivotal phase III clinical trial for treatment of patients in acute heart failure with renal impairment, the selective adenosine A1 receptor antagonist rolofylline has failed in every respect, and Merck has announced it will discontinue the drug's development.

Rolofylline had shown promise in an earlier 301-patient pilot study, with favorable effects on dyspnea and renal function and trends for lower mortality and readmission rates than with standard therapy, Dr. Marco Metra said at the annual congress of the European Society of Cardiology.

The negative findings in a definitive study for a drug with a novel mechanism of action are a setback in the effort to find new, more effective treatments for acute heart failure. AHF is the No. 1 cause of hospitalization in patients over age 65, it carries a dismal prognosis, and there have been no significant advances in its medical treatment, he said at a press conference in which he discussed the PROTECT trial.

Most patients who are hospitalized with AHF have underlying chronic kidney disease or experience worsening renal function during their hospital stay. This is associated with a worse prognosis. Adenosine mediates diuretic resistance and worsening renal function, so rolofylline, as a selective adenosine blocker, was an attractive drug, explained Dr. Metra of the University of Brescia (Italy).

In PROTECT, 2,033 patients were randomized 2:1 to 30 mg/day of intravenous rolofylline given over 4 hours for 3 days or placebo. All participants were hospitalized with signs of fluid overload requiring intravenous loop diuretics, mild to moderate impairment of renal function, and an elevated concentration of either brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide.

The primary outcome was treatment success, defined as moderate to marked improvement in dyspnea 24 and 48 hours after the start of treatment in the absence of persistent renal impairment or other negative outcomes. This was achieved in 41% of the rolofylline group and 36% of controls, a nonsignificant difference.

The drug proved to have no impact on the roughly 15% rate of persistent renal failure, the 60-day readmission rate of just under 26%, or 60-day mortality, which was 8.9% with rolofylline and 9.5% with placebo.

Particularly concerning was the finding that seizures or stroke occurred in 1.5% of the rolofylline group, compared with 0.6% of the placebo group, said Dr. Metra, who has been a consultant and advisory board member for Merck.

Seizures or stroke occurred in 1.5% of the rolofylline group, compared with 0.6% of the placebo group.

Source Dr. metra

BARCELONA — In its pivotal phase III clinical trial for treatment of patients in acute heart failure with renal impairment, the selective adenosine A1 receptor antagonist rolofylline has failed in every respect, and Merck has announced it will discontinue the drug's development.

Rolofylline had shown promise in an earlier 301-patient pilot study, with favorable effects on dyspnea and renal function and trends for lower mortality and readmission rates than with standard therapy, Dr. Marco Metra said at the annual congress of the European Society of Cardiology.

The negative findings in a definitive study for a drug with a novel mechanism of action are a setback in the effort to find new, more effective treatments for acute heart failure. AHF is the No. 1 cause of hospitalization in patients over age 65, it carries a dismal prognosis, and there have been no significant advances in its medical treatment, he said at a press conference in which he discussed the PROTECT trial.

Most patients who are hospitalized with AHF have underlying chronic kidney disease or experience worsening renal function during their hospital stay. This is associated with a worse prognosis. Adenosine mediates diuretic resistance and worsening renal function, so rolofylline, as a selective adenosine blocker, was an attractive drug, explained Dr. Metra of the University of Brescia (Italy).

In PROTECT, 2,033 patients were randomized 2:1 to 30 mg/day of intravenous rolofylline given over 4 hours for 3 days or placebo. All participants were hospitalized with signs of fluid overload requiring intravenous loop diuretics, mild to moderate impairment of renal function, and an elevated concentration of either brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide.

The primary outcome was treatment success, defined as moderate to marked improvement in dyspnea 24 and 48 hours after the start of treatment in the absence of persistent renal impairment or other negative outcomes. This was achieved in 41% of the rolofylline group and 36% of controls, a nonsignificant difference.

The drug proved to have no impact on the roughly 15% rate of persistent renal failure, the 60-day readmission rate of just under 26%, or 60-day mortality, which was 8.9% with rolofylline and 9.5% with placebo.

Particularly concerning was the finding that seizures or stroke occurred in 1.5% of the rolofylline group, compared with 0.6% of the placebo group, said Dr. Metra, who has been a consultant and advisory board member for Merck.

Seizures or stroke occurred in 1.5% of the rolofylline group, compared with 0.6% of the placebo group.

Source Dr. metra

BARCELONA — In its pivotal phase III clinical trial for treatment of patients in acute heart failure with renal impairment, the selective adenosine A1 receptor antagonist rolofylline has failed in every respect, and Merck has announced it will discontinue the drug's development.

Rolofylline had shown promise in an earlier 301-patient pilot study, with favorable effects on dyspnea and renal function and trends for lower mortality and readmission rates than with standard therapy, Dr. Marco Metra said at the annual congress of the European Society of Cardiology.

The negative findings in a definitive study for a drug with a novel mechanism of action are a setback in the effort to find new, more effective treatments for acute heart failure. AHF is the No. 1 cause of hospitalization in patients over age 65, it carries a dismal prognosis, and there have been no significant advances in its medical treatment, he said at a press conference in which he discussed the PROTECT trial.

Most patients who are hospitalized with AHF have underlying chronic kidney disease or experience worsening renal function during their hospital stay. This is associated with a worse prognosis. Adenosine mediates diuretic resistance and worsening renal function, so rolofylline, as a selective adenosine blocker, was an attractive drug, explained Dr. Metra of the University of Brescia (Italy).

In PROTECT, 2,033 patients were randomized 2:1 to 30 mg/day of intravenous rolofylline given over 4 hours for 3 days or placebo. All participants were hospitalized with signs of fluid overload requiring intravenous loop diuretics, mild to moderate impairment of renal function, and an elevated concentration of either brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide.

The primary outcome was treatment success, defined as moderate to marked improvement in dyspnea 24 and 48 hours after the start of treatment in the absence of persistent renal impairment or other negative outcomes. This was achieved in 41% of the rolofylline group and 36% of controls, a nonsignificant difference.

The drug proved to have no impact on the roughly 15% rate of persistent renal failure, the 60-day readmission rate of just under 26%, or 60-day mortality, which was 8.9% with rolofylline and 9.5% with placebo.

Particularly concerning was the finding that seizures or stroke occurred in 1.5% of the rolofylline group, compared with 0.6% of the placebo group, said Dr. Metra, who has been a consultant and advisory board member for Merck.

Seizures or stroke occurred in 1.5% of the rolofylline group, compared with 0.6% of the placebo group.

Source Dr. metra

BARCELONA — The common practice of discontinuing beta-blocker therapy during hospitalization for acute heart failure is counterproductive, according to a French randomized trial.

“During acute heart failure, beta-blocker therapy should be continued, because this practice is not associated with delayed or lesser improvement, and there is a higher rate of chronic beta-blocker therapy 3 months later, the benefits of which are well established,” Dr. Guillaume Jondeau concluded in presenting the results of the Beta Blocker Continuation Versus Interruption in Patients With Congestive Heart Failure Hospitalized for a Decompensation Episode (B-CONVINCED) trial at the annual congress of the European Society of Cardiology.

B-CONVINCED was conducted to redress the lack of level 1 evidence regarding the best clinical strategy when patients with systolic dysfunction who are on chronic beta-blocker therapy are hospitalized for acute heart failure (AHF). Many physicians, reasoning that the failing circulatory system needs adrenergic support, halve the dose or halt the drug altogether. The 2008 ESC guidelines state as a class IIA recommendation that “a reduction in the beta-blocker dose may be necessary. In severe situations, temporary discontinuation can be considered.”

B-CONVINCED, a noninferiority trial in 147 patients, hypothesized that continuing the beta-blocker would not result in worse outcomes than stoppage upon hospital admission. The primary end point was improvement in both dyspnea and general well being as assessed by blinded physicians 3 days into the hospitalization. This was achieved in 93% of the beta-blocker continuation group and 92% of the drug-halt group. Similarly, another round of blinded physician assessments after 8 days concluded 95% of patients in both study arms were significantly improved. Duration of hospital stay, patient self-assessments, and rehospitalization rates during the next 3 months were also similar in the two groups.

However, the proportion of patients on beta-blocker therapy 3 months after the acute exacerbation was significantly different: 90% in the continuation group and 76% in the discontinuation group. This reflects the reality that once beta-blocker therapy for AHF has been stopped, it can be a challenge to restart and titrate up to effective doses, said Dr. Jondeau of the University of Paris.

Discussant Karl Swedberg noted that there is a decades-long history of skepticism regarding the use of beta-blockers in heart failure. Yet today, they are the best-documented and most effective therapy for systolic heart failure.

B-CONVINCED provides the first solid randomized clinical trial evidence that sticking to the prehospitalization dose of a beta-blocker during an AHF exacerbation instead of halting the drug at admission should be the first-line strategy, said Dr. Swedberg, professor of cardiology at Sahlgrenska University Hospital, Goteborg, Sweden. “More patients will be on effective treatment at 3 months, and many lives will be saved by this strategy.”

The trial was funded by the French Ministry of Health. Neither Dr. Jondeau nor Dr. Swedberg disclosed any relationships with industry.

BARCELONA — The common practice of discontinuing beta-blocker therapy during hospitalization for acute heart failure is counterproductive, according to a French randomized trial.

“During acute heart failure, beta-blocker therapy should be continued, because this practice is not associated with delayed or lesser improvement, and there is a higher rate of chronic beta-blocker therapy 3 months later, the benefits of which are well established,” Dr. Guillaume Jondeau concluded in presenting the results of the Beta Blocker Continuation Versus Interruption in Patients With Congestive Heart Failure Hospitalized for a Decompensation Episode (B-CONVINCED) trial at the annual congress of the European Society of Cardiology.

B-CONVINCED was conducted to redress the lack of level 1 evidence regarding the best clinical strategy when patients with systolic dysfunction who are on chronic beta-blocker therapy are hospitalized for acute heart failure (AHF). Many physicians, reasoning that the failing circulatory system needs adrenergic support, halve the dose or halt the drug altogether. The 2008 ESC guidelines state as a class IIA recommendation that “a reduction in the beta-blocker dose may be necessary. In severe situations, temporary discontinuation can be considered.”

B-CONVINCED, a noninferiority trial in 147 patients, hypothesized that continuing the beta-blocker would not result in worse outcomes than stoppage upon hospital admission. The primary end point was improvement in both dyspnea and general well being as assessed by blinded physicians 3 days into the hospitalization. This was achieved in 93% of the beta-blocker continuation group and 92% of the drug-halt group. Similarly, another round of blinded physician assessments after 8 days concluded 95% of patients in both study arms were significantly improved. Duration of hospital stay, patient self-assessments, and rehospitalization rates during the next 3 months were also similar in the two groups.

However, the proportion of patients on beta-blocker therapy 3 months after the acute exacerbation was significantly different: 90% in the continuation group and 76% in the discontinuation group. This reflects the reality that once beta-blocker therapy for AHF has been stopped, it can be a challenge to restart and titrate up to effective doses, said Dr. Jondeau of the University of Paris.

Discussant Karl Swedberg noted that there is a decades-long history of skepticism regarding the use of beta-blockers in heart failure. Yet today, they are the best-documented and most effective therapy for systolic heart failure.

B-CONVINCED provides the first solid randomized clinical trial evidence that sticking to the prehospitalization dose of a beta-blocker during an AHF exacerbation instead of halting the drug at admission should be the first-line strategy, said Dr. Swedberg, professor of cardiology at Sahlgrenska University Hospital, Goteborg, Sweden. “More patients will be on effective treatment at 3 months, and many lives will be saved by this strategy.”

The trial was funded by the French Ministry of Health. Neither Dr. Jondeau nor Dr. Swedberg disclosed any relationships with industry.

BARCELONA — The common practice of discontinuing beta-blocker therapy during hospitalization for acute heart failure is counterproductive, according to a French randomized trial.

“During acute heart failure, beta-blocker therapy should be continued, because this practice is not associated with delayed or lesser improvement, and there is a higher rate of chronic beta-blocker therapy 3 months later, the benefits of which are well established,” Dr. Guillaume Jondeau concluded in presenting the results of the Beta Blocker Continuation Versus Interruption in Patients With Congestive Heart Failure Hospitalized for a Decompensation Episode (B-CONVINCED) trial at the annual congress of the European Society of Cardiology.

B-CONVINCED was conducted to redress the lack of level 1 evidence regarding the best clinical strategy when patients with systolic dysfunction who are on chronic beta-blocker therapy are hospitalized for acute heart failure (AHF). Many physicians, reasoning that the failing circulatory system needs adrenergic support, halve the dose or halt the drug altogether. The 2008 ESC guidelines state as a class IIA recommendation that “a reduction in the beta-blocker dose may be necessary. In severe situations, temporary discontinuation can be considered.”

B-CONVINCED, a noninferiority trial in 147 patients, hypothesized that continuing the beta-blocker would not result in worse outcomes than stoppage upon hospital admission. The primary end point was improvement in both dyspnea and general well being as assessed by blinded physicians 3 days into the hospitalization. This was achieved in 93% of the beta-blocker continuation group and 92% of the drug-halt group. Similarly, another round of blinded physician assessments after 8 days concluded 95% of patients in both study arms were significantly improved. Duration of hospital stay, patient self-assessments, and rehospitalization rates during the next 3 months were also similar in the two groups.

However, the proportion of patients on beta-blocker therapy 3 months after the acute exacerbation was significantly different: 90% in the continuation group and 76% in the discontinuation group. This reflects the reality that once beta-blocker therapy for AHF has been stopped, it can be a challenge to restart and titrate up to effective doses, said Dr. Jondeau of the University of Paris.

Discussant Karl Swedberg noted that there is a decades-long history of skepticism regarding the use of beta-blockers in heart failure. Yet today, they are the best-documented and most effective therapy for systolic heart failure.

B-CONVINCED provides the first solid randomized clinical trial evidence that sticking to the prehospitalization dose of a beta-blocker during an AHF exacerbation instead of halting the drug at admission should be the first-line strategy, said Dr. Swedberg, professor of cardiology at Sahlgrenska University Hospital, Goteborg, Sweden. “More patients will be on effective treatment at 3 months, and many lives will be saved by this strategy.”

The trial was funded by the French Ministry of Health. Neither Dr. Jondeau nor Dr. Swedberg disclosed any relationships with industry.

BOSTON — Monitoring fluid buildup in the chest by intrathoracic impedance is more predictive of events in heart failure patients than is daily weight monitoring, a multicenter, prospective, double-blind investigation has found.

Dr. William T. Abraham of Ohio State University, Columbus, and colleagues conducted the Fluid Accumulation Status Trial (FAST), comparing results of intrathoracic impedance monitoring with those of daily weight monitoring—the current standard of care—in 156 heart failure (HF) patients. The investigators used a drop in intrathoracic impedance as a surrogate to identify presymptomatic, treatable fluid buildup. Impedance changes were detected with software downloaded onto the patients' implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) devices.

All participants had HF symptoms for a mean of 18 months. At baseline, 85% were in New York Heart Association (NYHA) class II or III and most of the rest were in NYHA class I, Dr. Abraham reported in a late-breaking abstract presented at the annual meeting of the Heart Failure Society of America.

The investigators compared data collected by the impedance monitoring software and the patient-completed daily weight diaries. Impedance data were available nearly every day of the trial, but only 76% of the patients complied with daily weight monitoring, said Dr. Abraham.

Of the 65 HF events that occurred in 31 patients, intrathoracic impedance monitoring accurately predicted 48 of them; daily weight monitoring predicted 13. “The adjusted sensitivity for [impedance monitoring] was more than three times higher than with daily weight monitoring,” at 76% and 23%, respectively, he reported. Of the predicted events, 40 of those detected by impedance monitoring were not detected by weight monitoring and 5 of those detected by weight monitoring were not detected by fluid monitoring, Dr. Abraham said.

Both impedance and weight monitoring set off many false alarms. The impedance monitoring system identified 417 “impedance crossings,” which are the signals predicting an HF event, while there were 890 changes in weight that met the warning level criteria (at least three pounds gained in 1 day or at least five pounds gained over 3 days), Dr. Abraham said.

“With daily weight [monitoring], you have less sensitivity and more false alarms to respond to [compared with impedance monitoring],” suggesting that impedance status monitoring may be the better option and should be used in addition to the daily weight monitoring in patients with implanted devices that have this capability, he said.

The findings should not be considered in a vacuum, said Dr. Lynne Warner Stevenson of Brigham and Women's Hospital, Boston. “It's crucial that 88% of impedance crossings in this study were not associated with a following event. Responding to these could worsen renal function and lead to electrolyte derangements.”

Frequent such nonevents could blunt the system's responsiveness, she added. “If you keep seeing things go up, and nothing is happening, it would be like crying 'wolf.' It will be difficult to decide when we actually do need to intervene.”

FAST was sponsored by Medtronic Inc., maker of the OptiVol Fluid Status Monitoring System used in the study. Dr. Abraham has received research grants and/or consulting fees from Medtronic, Biotronik Inc., Boston Scientific Corp., and St. Jude Medical Inc. Dr. Stevenson has received funding and/or consulting fees from CardioMEMS Inc. and Medtronic.

BOSTON — Monitoring fluid buildup in the chest by intrathoracic impedance is more predictive of events in heart failure patients than is daily weight monitoring, a multicenter, prospective, double-blind investigation has found.

Dr. William T. Abraham of Ohio State University, Columbus, and colleagues conducted the Fluid Accumulation Status Trial (FAST), comparing results of intrathoracic impedance monitoring with those of daily weight monitoring—the current standard of care—in 156 heart failure (HF) patients. The investigators used a drop in intrathoracic impedance as a surrogate to identify presymptomatic, treatable fluid buildup. Impedance changes were detected with software downloaded onto the patients' implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) devices.

All participants had HF symptoms for a mean of 18 months. At baseline, 85% were in New York Heart Association (NYHA) class II or III and most of the rest were in NYHA class I, Dr. Abraham reported in a late-breaking abstract presented at the annual meeting of the Heart Failure Society of America.

The investigators compared data collected by the impedance monitoring software and the patient-completed daily weight diaries. Impedance data were available nearly every day of the trial, but only 76% of the patients complied with daily weight monitoring, said Dr. Abraham.

Of the 65 HF events that occurred in 31 patients, intrathoracic impedance monitoring accurately predicted 48 of them; daily weight monitoring predicted 13. “The adjusted sensitivity for [impedance monitoring] was more than three times higher than with daily weight monitoring,” at 76% and 23%, respectively, he reported. Of the predicted events, 40 of those detected by impedance monitoring were not detected by weight monitoring and 5 of those detected by weight monitoring were not detected by fluid monitoring, Dr. Abraham said.

Both impedance and weight monitoring set off many false alarms. The impedance monitoring system identified 417 “impedance crossings,” which are the signals predicting an HF event, while there were 890 changes in weight that met the warning level criteria (at least three pounds gained in 1 day or at least five pounds gained over 3 days), Dr. Abraham said.

“With daily weight [monitoring], you have less sensitivity and more false alarms to respond to [compared with impedance monitoring],” suggesting that impedance status monitoring may be the better option and should be used in addition to the daily weight monitoring in patients with implanted devices that have this capability, he said.

The findings should not be considered in a vacuum, said Dr. Lynne Warner Stevenson of Brigham and Women's Hospital, Boston. “It's crucial that 88% of impedance crossings in this study were not associated with a following event. Responding to these could worsen renal function and lead to electrolyte derangements.”

Frequent such nonevents could blunt the system's responsiveness, she added. “If you keep seeing things go up, and nothing is happening, it would be like crying 'wolf.' It will be difficult to decide when we actually do need to intervene.”

FAST was sponsored by Medtronic Inc., maker of the OptiVol Fluid Status Monitoring System used in the study. Dr. Abraham has received research grants and/or consulting fees from Medtronic, Biotronik Inc., Boston Scientific Corp., and St. Jude Medical Inc. Dr. Stevenson has received funding and/or consulting fees from CardioMEMS Inc. and Medtronic.

BOSTON — Monitoring fluid buildup in the chest by intrathoracic impedance is more predictive of events in heart failure patients than is daily weight monitoring, a multicenter, prospective, double-blind investigation has found.

Dr. William T. Abraham of Ohio State University, Columbus, and colleagues conducted the Fluid Accumulation Status Trial (FAST), comparing results of intrathoracic impedance monitoring with those of daily weight monitoring—the current standard of care—in 156 heart failure (HF) patients. The investigators used a drop in intrathoracic impedance as a surrogate to identify presymptomatic, treatable fluid buildup. Impedance changes were detected with software downloaded onto the patients' implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) devices.

All participants had HF symptoms for a mean of 18 months. At baseline, 85% were in New York Heart Association (NYHA) class II or III and most of the rest were in NYHA class I, Dr. Abraham reported in a late-breaking abstract presented at the annual meeting of the Heart Failure Society of America.

The investigators compared data collected by the impedance monitoring software and the patient-completed daily weight diaries. Impedance data were available nearly every day of the trial, but only 76% of the patients complied with daily weight monitoring, said Dr. Abraham.

Of the 65 HF events that occurred in 31 patients, intrathoracic impedance monitoring accurately predicted 48 of them; daily weight monitoring predicted 13. “The adjusted sensitivity for [impedance monitoring] was more than three times higher than with daily weight monitoring,” at 76% and 23%, respectively, he reported. Of the predicted events, 40 of those detected by impedance monitoring were not detected by weight monitoring and 5 of those detected by weight monitoring were not detected by fluid monitoring, Dr. Abraham said.

Both impedance and weight monitoring set off many false alarms. The impedance monitoring system identified 417 “impedance crossings,” which are the signals predicting an HF event, while there were 890 changes in weight that met the warning level criteria (at least three pounds gained in 1 day or at least five pounds gained over 3 days), Dr. Abraham said.

“With daily weight [monitoring], you have less sensitivity and more false alarms to respond to [compared with impedance monitoring],” suggesting that impedance status monitoring may be the better option and should be used in addition to the daily weight monitoring in patients with implanted devices that have this capability, he said.

The findings should not be considered in a vacuum, said Dr. Lynne Warner Stevenson of Brigham and Women's Hospital, Boston. “It's crucial that 88% of impedance crossings in this study were not associated with a following event. Responding to these could worsen renal function and lead to electrolyte derangements.”

Frequent such nonevents could blunt the system's responsiveness, she added. “If you keep seeing things go up, and nothing is happening, it would be like crying 'wolf.' It will be difficult to decide when we actually do need to intervene.”

FAST was sponsored by Medtronic Inc., maker of the OptiVol Fluid Status Monitoring System used in the study. Dr. Abraham has received research grants and/or consulting fees from Medtronic, Biotronik Inc., Boston Scientific Corp., and St. Jude Medical Inc. Dr. Stevenson has received funding and/or consulting fees from CardioMEMS Inc. and Medtronic.

NEW ORLEANS — A simple predictive instrument may improve emergency department disposition decisions regarding asymptomatic elderly patients who present with syncope.

The Syncope Risk Score defines a 10-fold gradient in the risk of delayed cardiac events among elderly ED patients with syncope, Dr. Benjamin Sun said at the annual meeting of the Society for Academic Emergency Medicine.

Patients whose score puts them in the low- or intermediate-risk categories may be reasonable candidates for discharge or a rapid ED observation unit. In contrast, those whose Syncope Risk Score places them in the high-risk group, with a 20% risk of a cardiac event during the next 30 days, probably should be admitted to the hospital, according to Dr. Sun of the University of California, Los Angeles.

The score relies upon one negative and six positive risk factors. All seven elements are readily obtainable in the first hour of an ED evaluation. A patient is assigned 1 point for each of the six factors conferring increased risk of delayed cardiac events, and minus 1 point for near syncope (see charts). The points are added up. A total score of 3-6 signifies high risk, 1-2 is intermediate, and 0 or −1 indicates low risk.

Dr. Sun developed the Syncope Risk Score through a retrospective cohort study of 2,871 asymptomatic geriatric patients, mean age 77 years, who visited any of three Southern California Kaiser Permanente EDs because of syncope and who did not have a serious underlying condition identified during their ED evaluation.

During the next 30 days, 170 patients experienced acute myocardial infarction, arrhythmia, coronary revascularization, or another delayed cardiac event. The seven independent predictors of these adverse outcomes that make up the Syncope Risk Score were derived via a multivariate logistic regression analysis that included more than 50 variables extracted from patients' medical charts.

The Syncope Risk Score is an attractively simple, quick tool, but before it is ready for prime-time clinical use in EDs it must be validated in an independent prospective study, Dr. Sun noted.

His development of the score was supported by the National Institutes of Health and the American Geriatrics Society.

Source ELSEVIER GLOBAL MEDICAL NEWS

Source ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — A simple predictive instrument may improve emergency department disposition decisions regarding asymptomatic elderly patients who present with syncope.

The Syncope Risk Score defines a 10-fold gradient in the risk of delayed cardiac events among elderly ED patients with syncope, Dr. Benjamin Sun said at the annual meeting of the Society for Academic Emergency Medicine.

Patients whose score puts them in the low- or intermediate-risk categories may be reasonable candidates for discharge or a rapid ED observation unit. In contrast, those whose Syncope Risk Score places them in the high-risk group, with a 20% risk of a cardiac event during the next 30 days, probably should be admitted to the hospital, according to Dr. Sun of the University of California, Los Angeles.

The score relies upon one negative and six positive risk factors. All seven elements are readily obtainable in the first hour of an ED evaluation. A patient is assigned 1 point for each of the six factors conferring increased risk of delayed cardiac events, and minus 1 point for near syncope (see charts). The points are added up. A total score of 3-6 signifies high risk, 1-2 is intermediate, and 0 or −1 indicates low risk.

Dr. Sun developed the Syncope Risk Score through a retrospective cohort study of 2,871 asymptomatic geriatric patients, mean age 77 years, who visited any of three Southern California Kaiser Permanente EDs because of syncope and who did not have a serious underlying condition identified during their ED evaluation.

During the next 30 days, 170 patients experienced acute myocardial infarction, arrhythmia, coronary revascularization, or another delayed cardiac event. The seven independent predictors of these adverse outcomes that make up the Syncope Risk Score were derived via a multivariate logistic regression analysis that included more than 50 variables extracted from patients' medical charts.

The Syncope Risk Score is an attractively simple, quick tool, but before it is ready for prime-time clinical use in EDs it must be validated in an independent prospective study, Dr. Sun noted.

His development of the score was supported by the National Institutes of Health and the American Geriatrics Society.

Source ELSEVIER GLOBAL MEDICAL NEWS

Source ELSEVIER GLOBAL MEDICAL NEWS

NEW ORLEANS — A simple predictive instrument may improve emergency department disposition decisions regarding asymptomatic elderly patients who present with syncope.

The Syncope Risk Score defines a 10-fold gradient in the risk of delayed cardiac events among elderly ED patients with syncope, Dr. Benjamin Sun said at the annual meeting of the Society for Academic Emergency Medicine.

Patients whose score puts them in the low- or intermediate-risk categories may be reasonable candidates for discharge or a rapid ED observation unit. In contrast, those whose Syncope Risk Score places them in the high-risk group, with a 20% risk of a cardiac event during the next 30 days, probably should be admitted to the hospital, according to Dr. Sun of the University of California, Los Angeles.

The score relies upon one negative and six positive risk factors. All seven elements are readily obtainable in the first hour of an ED evaluation. A patient is assigned 1 point for each of the six factors conferring increased risk of delayed cardiac events, and minus 1 point for near syncope (see charts). The points are added up. A total score of 3-6 signifies high risk, 1-2 is intermediate, and 0 or −1 indicates low risk.

Dr. Sun developed the Syncope Risk Score through a retrospective cohort study of 2,871 asymptomatic geriatric patients, mean age 77 years, who visited any of three Southern California Kaiser Permanente EDs because of syncope and who did not have a serious underlying condition identified during their ED evaluation.

During the next 30 days, 170 patients experienced acute myocardial infarction, arrhythmia, coronary revascularization, or another delayed cardiac event. The seven independent predictors of these adverse outcomes that make up the Syncope Risk Score were derived via a multivariate logistic regression analysis that included more than 50 variables extracted from patients' medical charts.

The Syncope Risk Score is an attractively simple, quick tool, but before it is ready for prime-time clinical use in EDs it must be validated in an independent prospective study, Dr. Sun noted.

His development of the score was supported by the National Institutes of Health and the American Geriatrics Society.

Source ELSEVIER GLOBAL MEDICAL NEWS

Source ELSEVIER GLOBAL MEDICAL NEWS

SAN DIEGO — Combining an electrocardiogram with serum N-terminal pro-B-type natriuretic peptide measurements is a simple, noninvasive way to diagnose pulmonary hypertension, results from an Austrian study suggest.

“Current pulmonary hypertension diagnosis guidelines say that ECG alone is not useful in the diagnosis of pulmonary hypertension. This is true,” Dr. Diana Bonderman said in an interview during a poster session at an international conference of the American Thoracic Society. “But if you combine ECG with NT-proBNP [N-terminal pro-B-type natriuretic peptide], it's going to be useful.”

The finding is important, she said, because the growing awareness of pulmonary hypertension PH, a high prevalence of postcapillary PH, and the inability to discern between pre- and postcapillary PH by transthoracic echocardiography (TTE) “have led to unnecessary right heart catheterizations.”

She and her associates prospectively analyzed data from 121 patients referred to the Medical University of Vienna between April 2007 and October 2008 for clinical and transthoracic echocardiographic suspicion of precapillary pulmonary hypertension (defined as having a systolic pulmonary artery pressure of at least 36 mm Hg). On admission, all patients underwent TTE, serum analysis including NT-proBNP, a 6-minute walk test, and blood gas analysis.

The patients were then assigned to one of two predicted diagnostic groups: precapillary PH (defined as right ventricular strain on ECG and/or serum NT-proBNP of greater than 80 pg/mL) or no precapillary PH (defined as no right ventricular strain on ECG and NT-proBNP of 80 pg/mL or less). Next, all patients underwent invasive hemodynamic measurements by right heart catheterization, and a final diagnosis was established.

The mean age of the patients was 62 years and 59% were female, reported Dr. Bonderman, a cardiologist at the Medical University of Vienna.

By right heart catheterization, 64 (53%) patients were diagnosed with precapillary PH. Precapillary PH was ruled out in 57 (47%) patients. By the diagnostic algorithm, 15 patients (12%) had been correctly allocated to the group without precapillary PH (true negatives). None of the allocations was a false negative.

“In the diagnostic pathway of PH, integration of the proposed algorithm subsequent to TTE may increase specificity from 0% to 19.3%, with a sensitivity of 100%,” the researchers wrote. “The incorporation of ECG and NT-proBNP into the workup of PH provides incremental diagnostic value and may significantly reduce the number of invasive assessments.”

The researchers had no conflicts to disclose.

SAN DIEGO — Combining an electrocardiogram with serum N-terminal pro-B-type natriuretic peptide measurements is a simple, noninvasive way to diagnose pulmonary hypertension, results from an Austrian study suggest.

“Current pulmonary hypertension diagnosis guidelines say that ECG alone is not useful in the diagnosis of pulmonary hypertension. This is true,” Dr. Diana Bonderman said in an interview during a poster session at an international conference of the American Thoracic Society. “But if you combine ECG with NT-proBNP [N-terminal pro-B-type natriuretic peptide], it's going to be useful.”

The finding is important, she said, because the growing awareness of pulmonary hypertension PH, a high prevalence of postcapillary PH, and the inability to discern between pre- and postcapillary PH by transthoracic echocardiography (TTE) “have led to unnecessary right heart catheterizations.”

She and her associates prospectively analyzed data from 121 patients referred to the Medical University of Vienna between April 2007 and October 2008 for clinical and transthoracic echocardiographic suspicion of precapillary pulmonary hypertension (defined as having a systolic pulmonary artery pressure of at least 36 mm Hg). On admission, all patients underwent TTE, serum analysis including NT-proBNP, a 6-minute walk test, and blood gas analysis.

The patients were then assigned to one of two predicted diagnostic groups: precapillary PH (defined as right ventricular strain on ECG and/or serum NT-proBNP of greater than 80 pg/mL) or no precapillary PH (defined as no right ventricular strain on ECG and NT-proBNP of 80 pg/mL or less). Next, all patients underwent invasive hemodynamic measurements by right heart catheterization, and a final diagnosis was established.

The mean age of the patients was 62 years and 59% were female, reported Dr. Bonderman, a cardiologist at the Medical University of Vienna.

By right heart catheterization, 64 (53%) patients were diagnosed with precapillary PH. Precapillary PH was ruled out in 57 (47%) patients. By the diagnostic algorithm, 15 patients (12%) had been correctly allocated to the group without precapillary PH (true negatives). None of the allocations was a false negative.

“In the diagnostic pathway of PH, integration of the proposed algorithm subsequent to TTE may increase specificity from 0% to 19.3%, with a sensitivity of 100%,” the researchers wrote. “The incorporation of ECG and NT-proBNP into the workup of PH provides incremental diagnostic value and may significantly reduce the number of invasive assessments.”

The researchers had no conflicts to disclose.

SAN DIEGO — Combining an electrocardiogram with serum N-terminal pro-B-type natriuretic peptide measurements is a simple, noninvasive way to diagnose pulmonary hypertension, results from an Austrian study suggest.

“Current pulmonary hypertension diagnosis guidelines say that ECG alone is not useful in the diagnosis of pulmonary hypertension. This is true,” Dr. Diana Bonderman said in an interview during a poster session at an international conference of the American Thoracic Society. “But if you combine ECG with NT-proBNP [N-terminal pro-B-type natriuretic peptide], it's going to be useful.”

The finding is important, she said, because the growing awareness of pulmonary hypertension PH, a high prevalence of postcapillary PH, and the inability to discern between pre- and postcapillary PH by transthoracic echocardiography (TTE) “have led to unnecessary right heart catheterizations.”

She and her associates prospectively analyzed data from 121 patients referred to the Medical University of Vienna between April 2007 and October 2008 for clinical and transthoracic echocardiographic suspicion of precapillary pulmonary hypertension (defined as having a systolic pulmonary artery pressure of at least 36 mm Hg). On admission, all patients underwent TTE, serum analysis including NT-proBNP, a 6-minute walk test, and blood gas analysis.

The patients were then assigned to one of two predicted diagnostic groups: precapillary PH (defined as right ventricular strain on ECG and/or serum NT-proBNP of greater than 80 pg/mL) or no precapillary PH (defined as no right ventricular strain on ECG and NT-proBNP of 80 pg/mL or less). Next, all patients underwent invasive hemodynamic measurements by right heart catheterization, and a final diagnosis was established.

The mean age of the patients was 62 years and 59% were female, reported Dr. Bonderman, a cardiologist at the Medical University of Vienna.

By right heart catheterization, 64 (53%) patients were diagnosed with precapillary PH. Precapillary PH was ruled out in 57 (47%) patients. By the diagnostic algorithm, 15 patients (12%) had been correctly allocated to the group without precapillary PH (true negatives). None of the allocations was a false negative.

“In the diagnostic pathway of PH, integration of the proposed algorithm subsequent to TTE may increase specificity from 0% to 19.3%, with a sensitivity of 100%,” the researchers wrote. “The incorporation of ECG and NT-proBNP into the workup of PH provides incremental diagnostic value and may significantly reduce the number of invasive assessments.”

The researchers had no conflicts to disclose.

CHICAGO — As in outpatients, cystatin C levels appear to offer additional prognostic information in patients admitted with heart failure exacerbations, according to an analysis of 240 consecutive inpatients.

Although there was no significant association between the serum protein levels on admission and the study's primary end point of length of hospitalization, cystatin C was more predictive of all-cause mortality and the combined end point of readmission or death than was creatinine, Dr. Daniel J. Brotman and his colleagues reported in a poster at the annual meeting of the Society of Hospital Medicine.

Patients in the highest quartile of cystatin C (mean 2.44 mg/L) were at significantly increased risk of death (hazard ratio 2.07) and of readmission or death (HR 1.61) during the first year after admission, compared with those in the lower three cystatin C quartiles (mean 0.66-1.43 mg/L).

The association between cystatin C and the risk of readmission or death remained significant on multivariate analysis after adjustment for age, race, gender, and creatinine level (HR 1.65), according to Dr. Brotman, director of the hospitalists program at Johns Hopkins Hospital in Baltimore. The relationship also remained significant when ejection fraction was included in the model.

Cystatin C level has been shown to be a stronger predictor of the risk of death and cardiovascular events in elderly patients, compared with creatinine level (N. Engl. J. Med. 2005;352:2049-60). Accumulating evidence also supports its use as an alternative and more sensitive endogenous marker, compared with serum creatinine, for the estimation of glomerular filtration rate.

In the current analysis, there was a trend toward increased risk of readmission or death (HR 1.44) for patients in the top quartile of creatinine (mean 2.0 mg/dL), compared with those in the lower three creatinine quartiles (1.0-1.3 mg/dL), but this difference did not reach statistical significance.

The combination of cystatin C and creatinine, however, was significantly more predictive of the combined end point of readmission or death than was either variable alone (HR 1.81).

“We are looking into whether serial changes in this biomarker during the course of hospitalization will have any potential clinical utility,” Dr. Brotman said in an interview. Clinical application is currently limited, as most labs do not routinely test for cystatin C.

Dr. Brotman disclosed receiving research funding from Siemens Healthcare Diagnostics Inc., serving on the hospitalist leadership panel for Quantia Communications LLC, and being on the advisory boards of several pharmaceutical companies.

The combination of cystatin C and creatinine was more predictive of readmission or death than was either one alone.

Source DR. BROTMAN

CHICAGO — As in outpatients, cystatin C levels appear to offer additional prognostic information in patients admitted with heart failure exacerbations, according to an analysis of 240 consecutive inpatients.

Although there was no significant association between the serum protein levels on admission and the study's primary end point of length of hospitalization, cystatin C was more predictive of all-cause mortality and the combined end point of readmission or death than was creatinine, Dr. Daniel J. Brotman and his colleagues reported in a poster at the annual meeting of the Society of Hospital Medicine.

Patients in the highest quartile of cystatin C (mean 2.44 mg/L) were at significantly increased risk of death (hazard ratio 2.07) and of readmission or death (HR 1.61) during the first year after admission, compared with those in the lower three cystatin C quartiles (mean 0.66-1.43 mg/L).

The association between cystatin C and the risk of readmission or death remained significant on multivariate analysis after adjustment for age, race, gender, and creatinine level (HR 1.65), according to Dr. Brotman, director of the hospitalists program at Johns Hopkins Hospital in Baltimore. The relationship also remained significant when ejection fraction was included in the model.

Cystatin C level has been shown to be a stronger predictor of the risk of death and cardiovascular events in elderly patients, compared with creatinine level (N. Engl. J. Med. 2005;352:2049-60). Accumulating evidence also supports its use as an alternative and more sensitive endogenous marker, compared with serum creatinine, for the estimation of glomerular filtration rate.

In the current analysis, there was a trend toward increased risk of readmission or death (HR 1.44) for patients in the top quartile of creatinine (mean 2.0 mg/dL), compared with those in the lower three creatinine quartiles (1.0-1.3 mg/dL), but this difference did not reach statistical significance.

The combination of cystatin C and creatinine, however, was significantly more predictive of the combined end point of readmission or death than was either variable alone (HR 1.81).

“We are looking into whether serial changes in this biomarker during the course of hospitalization will have any potential clinical utility,” Dr. Brotman said in an interview. Clinical application is currently limited, as most labs do not routinely test for cystatin C.

Dr. Brotman disclosed receiving research funding from Siemens Healthcare Diagnostics Inc., serving on the hospitalist leadership panel for Quantia Communications LLC, and being on the advisory boards of several pharmaceutical companies.

The combination of cystatin C and creatinine was more predictive of readmission or death than was either one alone.

Source DR. BROTMAN

CHICAGO — As in outpatients, cystatin C levels appear to offer additional prognostic information in patients admitted with heart failure exacerbations, according to an analysis of 240 consecutive inpatients.

Although there was no significant association between the serum protein levels on admission and the study's primary end point of length of hospitalization, cystatin C was more predictive of all-cause mortality and the combined end point of readmission or death than was creatinine, Dr. Daniel J. Brotman and his colleagues reported in a poster at the annual meeting of the Society of Hospital Medicine.

Patients in the highest quartile of cystatin C (mean 2.44 mg/L) were at significantly increased risk of death (hazard ratio 2.07) and of readmission or death (HR 1.61) during the first year after admission, compared with those in the lower three cystatin C quartiles (mean 0.66-1.43 mg/L).

The association between cystatin C and the risk of readmission or death remained significant on multivariate analysis after adjustment for age, race, gender, and creatinine level (HR 1.65), according to Dr. Brotman, director of the hospitalists program at Johns Hopkins Hospital in Baltimore. The relationship also remained significant when ejection fraction was included in the model.

Cystatin C level has been shown to be a stronger predictor of the risk of death and cardiovascular events in elderly patients, compared with creatinine level (N. Engl. J. Med. 2005;352:2049-60). Accumulating evidence also supports its use as an alternative and more sensitive endogenous marker, compared with serum creatinine, for the estimation of glomerular filtration rate.

In the current analysis, there was a trend toward increased risk of readmission or death (HR 1.44) for patients in the top quartile of creatinine (mean 2.0 mg/dL), compared with those in the lower three creatinine quartiles (1.0-1.3 mg/dL), but this difference did not reach statistical significance.

The combination of cystatin C and creatinine, however, was significantly more predictive of the combined end point of readmission or death than was either variable alone (HR 1.81).

“We are looking into whether serial changes in this biomarker during the course of hospitalization will have any potential clinical utility,” Dr. Brotman said in an interview. Clinical application is currently limited, as most labs do not routinely test for cystatin C.

Dr. Brotman disclosed receiving research funding from Siemens Healthcare Diagnostics Inc., serving on the hospitalist leadership panel for Quantia Communications LLC, and being on the advisory boards of several pharmaceutical companies.

The combination of cystatin C and creatinine was more predictive of readmission or death than was either one alone.

Source DR. BROTMAN

ORLANDO — Chronic vagus nerve stimulation delivered by an implantable device resulted in significant functional and quality of life improvements in patients with advanced heart failure in a first-in-man study.

The 32-patient trial documented significant reductions in heart rate, New York Heart Association functional class, and Minnesota Living With Heart Failure scores along with increased left ventricular ejection fraction and improved 6-minute walk distance at assessment after 3 months of treatment, Dr. Gaetano M. De Ferrari reported at the annual meeting of the American College of Cardiology.

All of these benefits were maintained at the 6-month mark (see box).

“We believe that a large controlled study is now warranted,” said Dr. De Ferrari, head of cardiac intensive care at San Matteo Polyclinic in Pavia, Italy.

Vagus nerve stimulation (VNS) is approved for drug-refractory epilepsy and drug-refractory depression. Dr. De Ferrari presented the first-ever experience with the therapy in heart failure patients.

The rationale for VNS as a novel therapy for heart failure lies in the observation that reduced vagal activity and increased sympathetic tone are associated with increased mortality following acute MI as well as in heart failure. Moreover, additional vagal withdrawal often precedes episodes of acute decompensated heart failure.

Animal studies conducted by Dr. De Ferrari and coworkers at the University of Pavia 2 decades ago showed that chronic VNS markedly reduced mortality in the setting of post-MI heart failure, the cardiologist reported.

In the new clinical trial, 32 participants with NYHA class II-III heart failure each had an investigational CardioFit stimulator made by BioControl, an Israeli company, implanted in the right upper chest under the clavicle. The device was connected to a cuff electrode wrapped around the right cervical vagus nerve. The system is capable of sensing the R wave and delivering one or more pulse-synchronous stimuli of 0.5-msec duration. The stimulatory pulses were delivered at an average amplitude of 4.1 mAmp. The device was on an average of 21% of the time.

In this study, intended to establish safety, six patients experienced minor treatment-related adverse events such as cough, pain at stimulation site, or voice difficulties, all of which resolved with device tuning or adaptation. In addition, there were two serious device-related adverse events: a case of postoperative pulmonary edema, and a surgical revision after device implantation.

While there was no control group in this early study, Dr. De Ferrari dismissed the notion that the observed benefits might be due to the placebo effect.

“Most often the placebo effect lasts a few months. It's unlikely to continue for a 6-month period,” he said.

He and his coworkers are now trying to pin down which patients with advanced heart failure are most likely to respond to VNS. The five diabetic patients in the study did not benefit. The best responders were patients with a slightly higher baseline heart rate and those who could tolerate more intensive vagal stimulation.

Discussant Marvin A. Konstam called chronic VNS an intriguing and promising new therapeutic approach.

“The opportunity for benefit from increasing vagal tone is multifactorial. In the very simplest of terms, just the reduction in heart rate may be beneficial. I think to this day we don't know for sure how much of the benefit of beta-blockade in heart failure may simply be heart rate reduction, so on that ground alone I think there's potential benefit. Also, there's a potential antiarrhythmic effect from increasing vagal tone,” said Dr. Konstam, professor of medicine at Tufts University, Boston.

Dr. De Ferrari replied that there are several additional plausible mechanisms of benefit for chronic VNS, including anti-apoptotic and anti-inflammatory effects.

He disclosed having received research grants from, and serving as a paid consultant to, BioControl.

VNS benefits were maintained after 6 months. 'We believe that a large controlled study is now warranted.' DR. DE FERRARI

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Chronic vagus nerve stimulation delivered by an implantable device resulted in significant functional and quality of life improvements in patients with advanced heart failure in a first-in-man study.

The 32-patient trial documented significant reductions in heart rate, New York Heart Association functional class, and Minnesota Living With Heart Failure scores along with increased left ventricular ejection fraction and improved 6-minute walk distance at assessment after 3 months of treatment, Dr. Gaetano M. De Ferrari reported at the annual meeting of the American College of Cardiology.

All of these benefits were maintained at the 6-month mark (see box).

“We believe that a large controlled study is now warranted,” said Dr. De Ferrari, head of cardiac intensive care at San Matteo Polyclinic in Pavia, Italy.

Vagus nerve stimulation (VNS) is approved for drug-refractory epilepsy and drug-refractory depression. Dr. De Ferrari presented the first-ever experience with the therapy in heart failure patients.

The rationale for VNS as a novel therapy for heart failure lies in the observation that reduced vagal activity and increased sympathetic tone are associated with increased mortality following acute MI as well as in heart failure. Moreover, additional vagal withdrawal often precedes episodes of acute decompensated heart failure.

Animal studies conducted by Dr. De Ferrari and coworkers at the University of Pavia 2 decades ago showed that chronic VNS markedly reduced mortality in the setting of post-MI heart failure, the cardiologist reported.

In the new clinical trial, 32 participants with NYHA class II-III heart failure each had an investigational CardioFit stimulator made by BioControl, an Israeli company, implanted in the right upper chest under the clavicle. The device was connected to a cuff electrode wrapped around the right cervical vagus nerve. The system is capable of sensing the R wave and delivering one or more pulse-synchronous stimuli of 0.5-msec duration. The stimulatory pulses were delivered at an average amplitude of 4.1 mAmp. The device was on an average of 21% of the time.

In this study, intended to establish safety, six patients experienced minor treatment-related adverse events such as cough, pain at stimulation site, or voice difficulties, all of which resolved with device tuning or adaptation. In addition, there were two serious device-related adverse events: a case of postoperative pulmonary edema, and a surgical revision after device implantation.

While there was no control group in this early study, Dr. De Ferrari dismissed the notion that the observed benefits might be due to the placebo effect.

“Most often the placebo effect lasts a few months. It's unlikely to continue for a 6-month period,” he said.

He and his coworkers are now trying to pin down which patients with advanced heart failure are most likely to respond to VNS. The five diabetic patients in the study did not benefit. The best responders were patients with a slightly higher baseline heart rate and those who could tolerate more intensive vagal stimulation.

Discussant Marvin A. Konstam called chronic VNS an intriguing and promising new therapeutic approach.

“The opportunity for benefit from increasing vagal tone is multifactorial. In the very simplest of terms, just the reduction in heart rate may be beneficial. I think to this day we don't know for sure how much of the benefit of beta-blockade in heart failure may simply be heart rate reduction, so on that ground alone I think there's potential benefit. Also, there's a potential antiarrhythmic effect from increasing vagal tone,” said Dr. Konstam, professor of medicine at Tufts University, Boston.

Dr. De Ferrari replied that there are several additional plausible mechanisms of benefit for chronic VNS, including anti-apoptotic and anti-inflammatory effects.

He disclosed having received research grants from, and serving as a paid consultant to, BioControl.

VNS benefits were maintained after 6 months. 'We believe that a large controlled study is now warranted.' DR. DE FERRARI

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Chronic vagus nerve stimulation delivered by an implantable device resulted in significant functional and quality of life improvements in patients with advanced heart failure in a first-in-man study.

The 32-patient trial documented significant reductions in heart rate, New York Heart Association functional class, and Minnesota Living With Heart Failure scores along with increased left ventricular ejection fraction and improved 6-minute walk distance at assessment after 3 months of treatment, Dr. Gaetano M. De Ferrari reported at the annual meeting of the American College of Cardiology.

All of these benefits were maintained at the 6-month mark (see box).

“We believe that a large controlled study is now warranted,” said Dr. De Ferrari, head of cardiac intensive care at San Matteo Polyclinic in Pavia, Italy.

Vagus nerve stimulation (VNS) is approved for drug-refractory epilepsy and drug-refractory depression. Dr. De Ferrari presented the first-ever experience with the therapy in heart failure patients.

The rationale for VNS as a novel therapy for heart failure lies in the observation that reduced vagal activity and increased sympathetic tone are associated with increased mortality following acute MI as well as in heart failure. Moreover, additional vagal withdrawal often precedes episodes of acute decompensated heart failure.

Animal studies conducted by Dr. De Ferrari and coworkers at the University of Pavia 2 decades ago showed that chronic VNS markedly reduced mortality in the setting of post-MI heart failure, the cardiologist reported.

In the new clinical trial, 32 participants with NYHA class II-III heart failure each had an investigational CardioFit stimulator made by BioControl, an Israeli company, implanted in the right upper chest under the clavicle. The device was connected to a cuff electrode wrapped around the right cervical vagus nerve. The system is capable of sensing the R wave and delivering one or more pulse-synchronous stimuli of 0.5-msec duration. The stimulatory pulses were delivered at an average amplitude of 4.1 mAmp. The device was on an average of 21% of the time.

In this study, intended to establish safety, six patients experienced minor treatment-related adverse events such as cough, pain at stimulation site, or voice difficulties, all of which resolved with device tuning or adaptation. In addition, there were two serious device-related adverse events: a case of postoperative pulmonary edema, and a surgical revision after device implantation.

While there was no control group in this early study, Dr. De Ferrari dismissed the notion that the observed benefits might be due to the placebo effect.

“Most often the placebo effect lasts a few months. It's unlikely to continue for a 6-month period,” he said.

He and his coworkers are now trying to pin down which patients with advanced heart failure are most likely to respond to VNS. The five diabetic patients in the study did not benefit. The best responders were patients with a slightly higher baseline heart rate and those who could tolerate more intensive vagal stimulation.

Discussant Marvin A. Konstam called chronic VNS an intriguing and promising new therapeutic approach.

“The opportunity for benefit from increasing vagal tone is multifactorial. In the very simplest of terms, just the reduction in heart rate may be beneficial. I think to this day we don't know for sure how much of the benefit of beta-blockade in heart failure may simply be heart rate reduction, so on that ground alone I think there's potential benefit. Also, there's a potential antiarrhythmic effect from increasing vagal tone,” said Dr. Konstam, professor of medicine at Tufts University, Boston.

Dr. De Ferrari replied that there are several additional plausible mechanisms of benefit for chronic VNS, including anti-apoptotic and anti-inflammatory effects.

He disclosed having received research grants from, and serving as a paid consultant to, BioControl.

VNS benefits were maintained after 6 months. 'We believe that a large controlled study is now warranted.' DR. DE FERRARI

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Cardiac contractility modulation, an innovative device therapy for advanced heart failure, significantly improved peak VO2, quality of life scores, and New York Heart Association functional class in the randomized 50-center FIX-HF-5 trial.

“I'm extremely encouraged by the results of this study, and I think there's a future for cardiac contractility modulation. It has the potential to be a real breakthrough,” Dr. William T. Abraham said at the annual meeting of the American College of Cardiology.

There's a hitch, however. The FIX-HF-5 trial did not meet its primary efficacy end point, which was achievement of at least a 20% improvement in anaerobic threshold on metabolic exercise testing. That end point, imposed by the Food and Drug Administration, has never been used as a pivotal outcome in a heart failure study, and in hindsight it was a poor choice, according to Dr. Abraham, professor of medicine, physiology, and cell biology, and director of cardiovascular medicine, at Ohio State University, Columbus.

“In other trials of metabolic exercise testing and heart failure there seems to be a disconnect between peak VO2 and anaerobic threshold. Peak VO2 may improve significantly with little or no change in anaerobic threshold. I just don't think it's the right measure of exercise capacity in heart failure. We'll look to use a different primary end point in our confirmatory study,” he explained.

Cardiac contractility monitoring (CCM) involves implantation of a pacemaker-like device with leads to the right heart. The device, known as the Optimizer III, delivers an electrical signal during the absolute refractory period of the cardiac cycle; thus, unlike a pacemaker, the Optimizer III signal does not initiate a heartbeat. Instead, it upregulates genes involved in cardiac calcium channels to boost cardiac contractility at a lower work level, thus improving overall cardiac efficiency. The system relies on a transcutaneously charged battery, promoting long device life.

FIT-HF-5 was an unblinded study in which 428 patients with advanced heart failure were placed on optimal medical therapy and randomized to receive the Optimizer III or not. Roughly 90% of participants were NYHA class III, the rest were class IV. The average QRS duration was 101 ms. The Optimizer III operated for 5 hours per day during the 12 months of follow-up.

A 20% or greater improvement in anaerobic threshold occurred in 17.6% of the CCM group and 11.7% of controls, a nonsignificant difference.

The real action involved the prespecified secondary end points—which in other heart failure trials with metabolic exercise testing have been the primary end points. Peak VO2 worsened over the course of the year in controls but improved in the CCM group, with a highly significant mean difference of 0.65 mL/kg per min between the two groups.

There was also a mean 10-point difference favoring the CCM group in quality of life as measured by the Minnesota Living With Heart Failure Questionnaire. “That meets or exceeds the benefit seen with other device or drug therapies,” Dr. Abraham noted.

More than 44% of the CCM group experienced at least a 1-grade improvement in NYHA functional class, which was nearly twice the rate in controls.

Roughly half of FIX-HF-5 participants were NYHA class III with a left ventricular ejection fraction of 25% or more. The magnitude of benefit with CCM seen in this subgroup exceeded that in other participants. For example, they had a mean 1.3 mL/kg per min advantage in peak VO2 compared with controls, which is better than that seen in the controlled trials of cardiac resynchronization therapy. These are the type of patients to be enrolled in the pivotal trial now being planned, according to the cardiologist.

Discussant Clyde W. Yancy, president-elect of the American Heart Association, observed that new therapies with novel mechanisms of action are desperately needed in the field of heart failure, and said he is pleased that further studies of CCM are planned. But he sounded a note of caution.

“This is a very provocative study, but by the same token there is something about CCM that bespeaks of an inotropic effect, so we have to continue to be very thoughtful and circumspect and follow up larger populations for a longer period of time,” said Dr. Yancy, medical director of the Baylor Heart and Vascular Institute, Dallas.

Dr. Abraham has received research grants and consulting fees from Impulse Dynamics, sponsor of FIT-HF-5.

ORLANDO — Cardiac contractility modulation, an innovative device therapy for advanced heart failure, significantly improved peak VO2, quality of life scores, and New York Heart Association functional class in the randomized 50-center FIX-HF-5 trial.

“I'm extremely encouraged by the results of this study, and I think there's a future for cardiac contractility modulation. It has the potential to be a real breakthrough,” Dr. William T. Abraham said at the annual meeting of the American College of Cardiology.

There's a hitch, however. The FIX-HF-5 trial did not meet its primary efficacy end point, which was achievement of at least a 20% improvement in anaerobic threshold on metabolic exercise testing. That end point, imposed by the Food and Drug Administration, has never been used as a pivotal outcome in a heart failure study, and in hindsight it was a poor choice, according to Dr. Abraham, professor of medicine, physiology, and cell biology, and director of cardiovascular medicine, at Ohio State University, Columbus.

“In other trials of metabolic exercise testing and heart failure there seems to be a disconnect between peak VO2 and anaerobic threshold. Peak VO2 may improve significantly with little or no change in anaerobic threshold. I just don't think it's the right measure of exercise capacity in heart failure. We'll look to use a different primary end point in our confirmatory study,” he explained.

Cardiac contractility monitoring (CCM) involves implantation of a pacemaker-like device with leads to the right heart. The device, known as the Optimizer III, delivers an electrical signal during the absolute refractory period of the cardiac cycle; thus, unlike a pacemaker, the Optimizer III signal does not initiate a heartbeat. Instead, it upregulates genes involved in cardiac calcium channels to boost cardiac contractility at a lower work level, thus improving overall cardiac efficiency. The system relies on a transcutaneously charged battery, promoting long device life.

FIT-HF-5 was an unblinded study in which 428 patients with advanced heart failure were placed on optimal medical therapy and randomized to receive the Optimizer III or not. Roughly 90% of participants were NYHA class III, the rest were class IV. The average QRS duration was 101 ms. The Optimizer III operated for 5 hours per day during the 12 months of follow-up.

A 20% or greater improvement in anaerobic threshold occurred in 17.6% of the CCM group and 11.7% of controls, a nonsignificant difference.

The real action involved the prespecified secondary end points—which in other heart failure trials with metabolic exercise testing have been the primary end points. Peak VO2 worsened over the course of the year in controls but improved in the CCM group, with a highly significant mean difference of 0.65 mL/kg per min between the two groups.

There was also a mean 10-point difference favoring the CCM group in quality of life as measured by the Minnesota Living With Heart Failure Questionnaire. “That meets or exceeds the benefit seen with other device or drug therapies,” Dr. Abraham noted.

More than 44% of the CCM group experienced at least a 1-grade improvement in NYHA functional class, which was nearly twice the rate in controls.

Roughly half of FIX-HF-5 participants were NYHA class III with a left ventricular ejection fraction of 25% or more. The magnitude of benefit with CCM seen in this subgroup exceeded that in other participants. For example, they had a mean 1.3 mL/kg per min advantage in peak VO2 compared with controls, which is better than that seen in the controlled trials of cardiac resynchronization therapy. These are the type of patients to be enrolled in the pivotal trial now being planned, according to the cardiologist.

Discussant Clyde W. Yancy, president-elect of the American Heart Association, observed that new therapies with novel mechanisms of action are desperately needed in the field of heart failure, and said he is pleased that further studies of CCM are planned. But he sounded a note of caution.

“This is a very provocative study, but by the same token there is something about CCM that bespeaks of an inotropic effect, so we have to continue to be very thoughtful and circumspect and follow up larger populations for a longer period of time,” said Dr. Yancy, medical director of the Baylor Heart and Vascular Institute, Dallas.

Dr. Abraham has received research grants and consulting fees from Impulse Dynamics, sponsor of FIT-HF-5.

ORLANDO — Cardiac contractility modulation, an innovative device therapy for advanced heart failure, significantly improved peak VO2, quality of life scores, and New York Heart Association functional class in the randomized 50-center FIX-HF-5 trial.

“I'm extremely encouraged by the results of this study, and I think there's a future for cardiac contractility modulation. It has the potential to be a real breakthrough,” Dr. William T. Abraham said at the annual meeting of the American College of Cardiology.

There's a hitch, however. The FIX-HF-5 trial did not meet its primary efficacy end point, which was achievement of at least a 20% improvement in anaerobic threshold on metabolic exercise testing. That end point, imposed by the Food and Drug Administration, has never been used as a pivotal outcome in a heart failure study, and in hindsight it was a poor choice, according to Dr. Abraham, professor of medicine, physiology, and cell biology, and director of cardiovascular medicine, at Ohio State University, Columbus.

“In other trials of metabolic exercise testing and heart failure there seems to be a disconnect between peak VO2 and anaerobic threshold. Peak VO2 may improve significantly with little or no change in anaerobic threshold. I just don't think it's the right measure of exercise capacity in heart failure. We'll look to use a different primary end point in our confirmatory study,” he explained.

Cardiac contractility monitoring (CCM) involves implantation of a pacemaker-like device with leads to the right heart. The device, known as the Optimizer III, delivers an electrical signal during the absolute refractory period of the cardiac cycle; thus, unlike a pacemaker, the Optimizer III signal does not initiate a heartbeat. Instead, it upregulates genes involved in cardiac calcium channels to boost cardiac contractility at a lower work level, thus improving overall cardiac efficiency. The system relies on a transcutaneously charged battery, promoting long device life.

FIT-HF-5 was an unblinded study in which 428 patients with advanced heart failure were placed on optimal medical therapy and randomized to receive the Optimizer III or not. Roughly 90% of participants were NYHA class III, the rest were class IV. The average QRS duration was 101 ms. The Optimizer III operated for 5 hours per day during the 12 months of follow-up.

A 20% or greater improvement in anaerobic threshold occurred in 17.6% of the CCM group and 11.7% of controls, a nonsignificant difference.

The real action involved the prespecified secondary end points—which in other heart failure trials with metabolic exercise testing have been the primary end points. Peak VO2 worsened over the course of the year in controls but improved in the CCM group, with a highly significant mean difference of 0.65 mL/kg per min between the two groups.

There was also a mean 10-point difference favoring the CCM group in quality of life as measured by the Minnesota Living With Heart Failure Questionnaire. “That meets or exceeds the benefit seen with other device or drug therapies,” Dr. Abraham noted.

More than 44% of the CCM group experienced at least a 1-grade improvement in NYHA functional class, which was nearly twice the rate in controls.

Roughly half of FIX-HF-5 participants were NYHA class III with a left ventricular ejection fraction of 25% or more. The magnitude of benefit with CCM seen in this subgroup exceeded that in other participants. For example, they had a mean 1.3 mL/kg per min advantage in peak VO2 compared with controls, which is better than that seen in the controlled trials of cardiac resynchronization therapy. These are the type of patients to be enrolled in the pivotal trial now being planned, according to the cardiologist.

Discussant Clyde W. Yancy, president-elect of the American Heart Association, observed that new therapies with novel mechanisms of action are desperately needed in the field of heart failure, and said he is pleased that further studies of CCM are planned. But he sounded a note of caution.

“This is a very provocative study, but by the same token there is something about CCM that bespeaks of an inotropic effect, so we have to continue to be very thoughtful and circumspect and follow up larger populations for a longer period of time,” said Dr. Yancy, medical director of the Baylor Heart and Vascular Institute, Dallas.

Dr. Abraham has received research grants and consulting fees from Impulse Dynamics, sponsor of FIT-HF-5.