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VIDEO: Treating heart failure congestion improved hyperglycemia
SAN DIEGO – Congestion secondary to advanced heart failure appears to cause type 2 diabetes in a significant subgroup of patients, based on suggestive findings from a series of recently reported studies, Dr. Maya Guglin said during an interview at the annual meeting of the American College of Cardiology.
Dr. Guglin reviewed convergent findings from several groups of patients who received left ventricular assist devices to treat advanced heart failure. The analyses all showed that many, though not a majority, of those patients also had type 2 diabetes. Soon after patients received an assist device, the type 2 diabetes uniformly improved – and in many cases, glycemic control normalized.
Dr. Guglin, who has named this condition “cardiogenic diabetes,” said that reducing congestion with an assist device or with diuretic treatment seems the best way to both reduce congestion and improve or resolve the diabetes.
Those treatments will “improve quality of life, reduce hospital admissions for heart failure, and also improve the course of diabetes,” said Dr. Guglin, professor of medicine and medical director of the ventricular assist device program at the University of Kentucky in Lexington.
Dr. Guglin had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
SAN DIEGO – Congestion secondary to advanced heart failure appears to cause type 2 diabetes in a significant subgroup of patients, based on suggestive findings from a series of recently reported studies, Dr. Maya Guglin said during an interview at the annual meeting of the American College of Cardiology.
Dr. Guglin reviewed convergent findings from several groups of patients who received left ventricular assist devices to treat advanced heart failure. The analyses all showed that many, though not a majority, of those patients also had type 2 diabetes. Soon after patients received an assist device, the type 2 diabetes uniformly improved – and in many cases, glycemic control normalized.
Dr. Guglin, who has named this condition “cardiogenic diabetes,” said that reducing congestion with an assist device or with diuretic treatment seems the best way to both reduce congestion and improve or resolve the diabetes.
Those treatments will “improve quality of life, reduce hospital admissions for heart failure, and also improve the course of diabetes,” said Dr. Guglin, professor of medicine and medical director of the ventricular assist device program at the University of Kentucky in Lexington.
Dr. Guglin had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
SAN DIEGO – Congestion secondary to advanced heart failure appears to cause type 2 diabetes in a significant subgroup of patients, based on suggestive findings from a series of recently reported studies, Dr. Maya Guglin said during an interview at the annual meeting of the American College of Cardiology.
Dr. Guglin reviewed convergent findings from several groups of patients who received left ventricular assist devices to treat advanced heart failure. The analyses all showed that many, though not a majority, of those patients also had type 2 diabetes. Soon after patients received an assist device, the type 2 diabetes uniformly improved – and in many cases, glycemic control normalized.
Dr. Guglin, who has named this condition “cardiogenic diabetes,” said that reducing congestion with an assist device or with diuretic treatment seems the best way to both reduce congestion and improve or resolve the diabetes.
Those treatments will “improve quality of life, reduce hospital admissions for heart failure, and also improve the course of diabetes,” said Dr. Guglin, professor of medicine and medical director of the ventricular assist device program at the University of Kentucky in Lexington.
Dr. Guglin had no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM ACC 15
Ablation during mitral valve surgery offers up mixed results
SAN DIEGO – Surgical ablation of atrial fibrillation at the time of mitral valve surgery provides significantly greater rhythm control than mitral valve surgery alone, a study showed.
Freedom from atrial fibrillation (AF) at both 6 months and 1 year was 63% in patients undergoing mitral valve surgery (MVS) plus ablation and 29% in those undergoing MVS alone, a statistically significant difference.
However, patients who had ablation plus MVS were 2.5 times more likely to have a permanent pacemaker implanted than were those who had MVS alone, at 21.5% and 8.1%, respectively, also a significant difference.
Ablation did not increase mortality or major adverse cardiac or cerebrovascular events, Dr. A. Marc Gillinov said at the annual meeting of the American College of Cardiology.
Preoperative AF is present in up to 50% of patients undergoing mitral valve operations and is associated with an increased risk of death and stroke.
The study enrolled 260 relatively elderly patients (mean age 69 years) with AF that was persistent (non–self-terminating for at least 7 days) or long-standing persistent (continuous for at least a year), in addition to mitral valve disease. A total of 133 patients were randomly assigned to MVS plus ablation and 127 to MVS alone. The ablation group was further randomized to pulmonary vein isolation or a biatrial maze procedure; all underwent closure of the left atrial appendage.
There was no significant difference in freedom from AF at 6 months and 1 year between patients who had pulmonary vein isolation or a biatrial maze procedure, at 61% and 66%, respectively, said Dr. Gillinov, a cardiac surgeon at Cleveland Clinic.
One-year mortality was similar among all patients undergoing MVS plus ablation vs. MVS alone, at 6.8% and 8.7%.
The two groups also had similar Short Form-12 questionnaire scores for physical function and mental function, although AF occurring at least once daily was significantly less common with ablation, at 19.8%, compared with 45.2% in the MVS-alone patients, he said.
The heart rhythm endpoint was “stringent,” with 3-day Holter monitors obtained at both 6 and 12 months and repeat ablation procedures and death considered treatment failures, Dr. Gillinov said.
He acknowledged that 20% of patients did not have data for the primary endpoint and that the endpoint was not a clinical one, but said a trial with mortality or stroke as the endpoint would require more than 1,000 patients and many years follow-up.
Regarding whether ablation should now be performed routinely, “the glass is half full or half empty,” remarked discussant Dr. Bernard Gersh of Mayo Clinic in Rochester, Minn. “On one hand, you have shown less atrial fibrillation [with ablation], but no effect on quality of life, and the price to be paid was a higher rate of pacemaker implantation,” he said.
The pacemaker implantation rate was higher than expected – 17% in-hospital – and does represent a potential cost, but he would routinely do a maze procedure, Dr. Gillinov said.
Discussant Dr. Alice Jacobs of the Cardiovascular Center at Boston Medical Center, said she expected Dr. Gillinov to say the procedure should not be used in everyone given the lack of benefit in stroke, probably because they tied off the left atrium appendage, and the increase in pacemaker implantations.
About half of the pacemaker implantations were due to atrioventricular block, possibly a consequence of the valve surgery, and one-third to sinus-node dysfunction, which is common in elderly patients, Dr. Gillinov explained.
The study was funded by the National Institutes of Health and the Canadian Institutes of Health Research. Dr. Gillinov reported serving as a consultant/speaker for AtriCure, Medtronic, On-X, Edwards, and Tendyne; research funding from St. Jude Medical; an equity interest in Clear Catheter; and that his institution receives royalties from AtriCure for a left atrial appendage occlusion device.
SAN DIEGO – Surgical ablation of atrial fibrillation at the time of mitral valve surgery provides significantly greater rhythm control than mitral valve surgery alone, a study showed.
Freedom from atrial fibrillation (AF) at both 6 months and 1 year was 63% in patients undergoing mitral valve surgery (MVS) plus ablation and 29% in those undergoing MVS alone, a statistically significant difference.
However, patients who had ablation plus MVS were 2.5 times more likely to have a permanent pacemaker implanted than were those who had MVS alone, at 21.5% and 8.1%, respectively, also a significant difference.
Ablation did not increase mortality or major adverse cardiac or cerebrovascular events, Dr. A. Marc Gillinov said at the annual meeting of the American College of Cardiology.
Preoperative AF is present in up to 50% of patients undergoing mitral valve operations and is associated with an increased risk of death and stroke.
The study enrolled 260 relatively elderly patients (mean age 69 years) with AF that was persistent (non–self-terminating for at least 7 days) or long-standing persistent (continuous for at least a year), in addition to mitral valve disease. A total of 133 patients were randomly assigned to MVS plus ablation and 127 to MVS alone. The ablation group was further randomized to pulmonary vein isolation or a biatrial maze procedure; all underwent closure of the left atrial appendage.
There was no significant difference in freedom from AF at 6 months and 1 year between patients who had pulmonary vein isolation or a biatrial maze procedure, at 61% and 66%, respectively, said Dr. Gillinov, a cardiac surgeon at Cleveland Clinic.
One-year mortality was similar among all patients undergoing MVS plus ablation vs. MVS alone, at 6.8% and 8.7%.
The two groups also had similar Short Form-12 questionnaire scores for physical function and mental function, although AF occurring at least once daily was significantly less common with ablation, at 19.8%, compared with 45.2% in the MVS-alone patients, he said.
The heart rhythm endpoint was “stringent,” with 3-day Holter monitors obtained at both 6 and 12 months and repeat ablation procedures and death considered treatment failures, Dr. Gillinov said.
He acknowledged that 20% of patients did not have data for the primary endpoint and that the endpoint was not a clinical one, but said a trial with mortality or stroke as the endpoint would require more than 1,000 patients and many years follow-up.
Regarding whether ablation should now be performed routinely, “the glass is half full or half empty,” remarked discussant Dr. Bernard Gersh of Mayo Clinic in Rochester, Minn. “On one hand, you have shown less atrial fibrillation [with ablation], but no effect on quality of life, and the price to be paid was a higher rate of pacemaker implantation,” he said.
The pacemaker implantation rate was higher than expected – 17% in-hospital – and does represent a potential cost, but he would routinely do a maze procedure, Dr. Gillinov said.
Discussant Dr. Alice Jacobs of the Cardiovascular Center at Boston Medical Center, said she expected Dr. Gillinov to say the procedure should not be used in everyone given the lack of benefit in stroke, probably because they tied off the left atrium appendage, and the increase in pacemaker implantations.
About half of the pacemaker implantations were due to atrioventricular block, possibly a consequence of the valve surgery, and one-third to sinus-node dysfunction, which is common in elderly patients, Dr. Gillinov explained.
The study was funded by the National Institutes of Health and the Canadian Institutes of Health Research. Dr. Gillinov reported serving as a consultant/speaker for AtriCure, Medtronic, On-X, Edwards, and Tendyne; research funding from St. Jude Medical; an equity interest in Clear Catheter; and that his institution receives royalties from AtriCure for a left atrial appendage occlusion device.
SAN DIEGO – Surgical ablation of atrial fibrillation at the time of mitral valve surgery provides significantly greater rhythm control than mitral valve surgery alone, a study showed.
Freedom from atrial fibrillation (AF) at both 6 months and 1 year was 63% in patients undergoing mitral valve surgery (MVS) plus ablation and 29% in those undergoing MVS alone, a statistically significant difference.
However, patients who had ablation plus MVS were 2.5 times more likely to have a permanent pacemaker implanted than were those who had MVS alone, at 21.5% and 8.1%, respectively, also a significant difference.
Ablation did not increase mortality or major adverse cardiac or cerebrovascular events, Dr. A. Marc Gillinov said at the annual meeting of the American College of Cardiology.
Preoperative AF is present in up to 50% of patients undergoing mitral valve operations and is associated with an increased risk of death and stroke.
The study enrolled 260 relatively elderly patients (mean age 69 years) with AF that was persistent (non–self-terminating for at least 7 days) or long-standing persistent (continuous for at least a year), in addition to mitral valve disease. A total of 133 patients were randomly assigned to MVS plus ablation and 127 to MVS alone. The ablation group was further randomized to pulmonary vein isolation or a biatrial maze procedure; all underwent closure of the left atrial appendage.
There was no significant difference in freedom from AF at 6 months and 1 year between patients who had pulmonary vein isolation or a biatrial maze procedure, at 61% and 66%, respectively, said Dr. Gillinov, a cardiac surgeon at Cleveland Clinic.
One-year mortality was similar among all patients undergoing MVS plus ablation vs. MVS alone, at 6.8% and 8.7%.
The two groups also had similar Short Form-12 questionnaire scores for physical function and mental function, although AF occurring at least once daily was significantly less common with ablation, at 19.8%, compared with 45.2% in the MVS-alone patients, he said.
The heart rhythm endpoint was “stringent,” with 3-day Holter monitors obtained at both 6 and 12 months and repeat ablation procedures and death considered treatment failures, Dr. Gillinov said.
He acknowledged that 20% of patients did not have data for the primary endpoint and that the endpoint was not a clinical one, but said a trial with mortality or stroke as the endpoint would require more than 1,000 patients and many years follow-up.
Regarding whether ablation should now be performed routinely, “the glass is half full or half empty,” remarked discussant Dr. Bernard Gersh of Mayo Clinic in Rochester, Minn. “On one hand, you have shown less atrial fibrillation [with ablation], but no effect on quality of life, and the price to be paid was a higher rate of pacemaker implantation,” he said.
The pacemaker implantation rate was higher than expected – 17% in-hospital – and does represent a potential cost, but he would routinely do a maze procedure, Dr. Gillinov said.
Discussant Dr. Alice Jacobs of the Cardiovascular Center at Boston Medical Center, said she expected Dr. Gillinov to say the procedure should not be used in everyone given the lack of benefit in stroke, probably because they tied off the left atrium appendage, and the increase in pacemaker implantations.
About half of the pacemaker implantations were due to atrioventricular block, possibly a consequence of the valve surgery, and one-third to sinus-node dysfunction, which is common in elderly patients, Dr. Gillinov explained.
The study was funded by the National Institutes of Health and the Canadian Institutes of Health Research. Dr. Gillinov reported serving as a consultant/speaker for AtriCure, Medtronic, On-X, Edwards, and Tendyne; research funding from St. Jude Medical; an equity interest in Clear Catheter; and that his institution receives royalties from AtriCure for a left atrial appendage occlusion device.
AT ACC 15
Key clinical point: Surgical ablation of atrial fibrillation during mitral valve surgery decreases AF at 6 months and 1 year, but increases pacemaker implantations.
Major finding: Freedom from AF at both 6 months and 1 year was 63% with mitral valve surgery plus ablation and 29% for MVS alone.
Data source: Prospective, randomized study in 260 patients with persistent or longstanding persistent AF who required mitral valve surgery.
Disclosures: The study was funded by the National Institutes of Health and the Canadian Institutes of Health Research. Dr. Gillinov reported serving as a consultant/speaker for AtriCure, Medtronic, On-X, Edwards, and Tendyne; research funding from St. Jude Medical; an equity interest in Clear Catheter; and that his institution receives royalties from AtriCure for a left atrial appendage occlusion device.
Anxiety hits 42% of adults with congenital heart disease
SAN DIEGO– Elevated symptoms of anxiety are markedly more common than depression in adults with congenital heart disease, Lisa Deng reported at the annual meeting of the American College of Cardiology.
This observation isn’t reflected in the ACC/American Heart Association guidelines on the management of adult congenital heart disease (ACHD), which recommend that “a careful assessment of depressive symptoms and their possible overlap with symptoms of medical illness or side effects of medications must be part of the clinical evaluation of ACHD patients” (J. Am. Coll. Cardiol. 2008;52:e143-263).
Anxiety and depression have been shown to be associated with worse clinical outcomes in patients with heart disease. Given the high prevalence, deleterious impact, and treatable nature of anxiety symptoms, it makes sense to incorporate evaluation for both anxiety and depression in the clinical assessment of ACHD patients, according to Ms. Deng of Children’s Hospital of Philadelphia.
She reported on 134 patients (mean age, 35 years) attending an outpatient ACHD clinic, where they were assessed using the validated Hospital Anxiety and Depression Scale (HADS), the Satisfaction with Life Scale (SLS), and the Linear Analog Scale for Quality of Life (LAS). Of those patients, 45% had a history of arrhythmia and 20% had heart failure; 42% of subjects demonstrated elevated levels of anxiety as reflected in a HADS-Anxiety score of 8 or more out of a possible 21. In contrast, 12% had an elevated HADS-Depression score of 8 or more. Thus, anxiety was 3.5-fold more common than depression.
Of note, 15 of the 16 patients with depression had comorbid elevated levels of anxiety, but even though 42% of the ACHD patients had elevated anxiety scores, only 1 in 8 study participants had a note in their chart mentioning anxiety.
Patients with elevated anxiety reported significantly lower ratings than those with a HADS-Anxiety score of less than 8 on one quality-of-life measure – the SLS – but not on the LAS. In contrast, patients with depression scored significantly lower on both quality-of-life measures.
The clinical correlates of anxiety and depression differed in these ACHD patients. Half of the patients with elevated anxiety scores had a history of two or more surgical or interventional procedures, compared with 25% of subjects with a normal-range HADS-Anxiety score. One-fourth of patients with high depression scores were unemployed, a prevalence threefold greater than in nondepressive individuals. Also, 19% of patients with a HADS-Depression score of 8 or more had a history of arrhythmia, compared with 7% of nondepressive patients.
This study was supported by a research grant from Big Hearts in Little Bodies. Ms. Deng reported having no financial conflicts.
SAN DIEGO– Elevated symptoms of anxiety are markedly more common than depression in adults with congenital heart disease, Lisa Deng reported at the annual meeting of the American College of Cardiology.
This observation isn’t reflected in the ACC/American Heart Association guidelines on the management of adult congenital heart disease (ACHD), which recommend that “a careful assessment of depressive symptoms and their possible overlap with symptoms of medical illness or side effects of medications must be part of the clinical evaluation of ACHD patients” (J. Am. Coll. Cardiol. 2008;52:e143-263).
Anxiety and depression have been shown to be associated with worse clinical outcomes in patients with heart disease. Given the high prevalence, deleterious impact, and treatable nature of anxiety symptoms, it makes sense to incorporate evaluation for both anxiety and depression in the clinical assessment of ACHD patients, according to Ms. Deng of Children’s Hospital of Philadelphia.
She reported on 134 patients (mean age, 35 years) attending an outpatient ACHD clinic, where they were assessed using the validated Hospital Anxiety and Depression Scale (HADS), the Satisfaction with Life Scale (SLS), and the Linear Analog Scale for Quality of Life (LAS). Of those patients, 45% had a history of arrhythmia and 20% had heart failure; 42% of subjects demonstrated elevated levels of anxiety as reflected in a HADS-Anxiety score of 8 or more out of a possible 21. In contrast, 12% had an elevated HADS-Depression score of 8 or more. Thus, anxiety was 3.5-fold more common than depression.
Of note, 15 of the 16 patients with depression had comorbid elevated levels of anxiety, but even though 42% of the ACHD patients had elevated anxiety scores, only 1 in 8 study participants had a note in their chart mentioning anxiety.
Patients with elevated anxiety reported significantly lower ratings than those with a HADS-Anxiety score of less than 8 on one quality-of-life measure – the SLS – but not on the LAS. In contrast, patients with depression scored significantly lower on both quality-of-life measures.
The clinical correlates of anxiety and depression differed in these ACHD patients. Half of the patients with elevated anxiety scores had a history of two or more surgical or interventional procedures, compared with 25% of subjects with a normal-range HADS-Anxiety score. One-fourth of patients with high depression scores were unemployed, a prevalence threefold greater than in nondepressive individuals. Also, 19% of patients with a HADS-Depression score of 8 or more had a history of arrhythmia, compared with 7% of nondepressive patients.
This study was supported by a research grant from Big Hearts in Little Bodies. Ms. Deng reported having no financial conflicts.
SAN DIEGO– Elevated symptoms of anxiety are markedly more common than depression in adults with congenital heart disease, Lisa Deng reported at the annual meeting of the American College of Cardiology.
This observation isn’t reflected in the ACC/American Heart Association guidelines on the management of adult congenital heart disease (ACHD), which recommend that “a careful assessment of depressive symptoms and their possible overlap with symptoms of medical illness or side effects of medications must be part of the clinical evaluation of ACHD patients” (J. Am. Coll. Cardiol. 2008;52:e143-263).
Anxiety and depression have been shown to be associated with worse clinical outcomes in patients with heart disease. Given the high prevalence, deleterious impact, and treatable nature of anxiety symptoms, it makes sense to incorporate evaluation for both anxiety and depression in the clinical assessment of ACHD patients, according to Ms. Deng of Children’s Hospital of Philadelphia.
She reported on 134 patients (mean age, 35 years) attending an outpatient ACHD clinic, where they were assessed using the validated Hospital Anxiety and Depression Scale (HADS), the Satisfaction with Life Scale (SLS), and the Linear Analog Scale for Quality of Life (LAS). Of those patients, 45% had a history of arrhythmia and 20% had heart failure; 42% of subjects demonstrated elevated levels of anxiety as reflected in a HADS-Anxiety score of 8 or more out of a possible 21. In contrast, 12% had an elevated HADS-Depression score of 8 or more. Thus, anxiety was 3.5-fold more common than depression.
Of note, 15 of the 16 patients with depression had comorbid elevated levels of anxiety, but even though 42% of the ACHD patients had elevated anxiety scores, only 1 in 8 study participants had a note in their chart mentioning anxiety.
Patients with elevated anxiety reported significantly lower ratings than those with a HADS-Anxiety score of less than 8 on one quality-of-life measure – the SLS – but not on the LAS. In contrast, patients with depression scored significantly lower on both quality-of-life measures.
The clinical correlates of anxiety and depression differed in these ACHD patients. Half of the patients with elevated anxiety scores had a history of two or more surgical or interventional procedures, compared with 25% of subjects with a normal-range HADS-Anxiety score. One-fourth of patients with high depression scores were unemployed, a prevalence threefold greater than in nondepressive individuals. Also, 19% of patients with a HADS-Depression score of 8 or more had a history of arrhythmia, compared with 7% of nondepressive patients.
This study was supported by a research grant from Big Hearts in Little Bodies. Ms. Deng reported having no financial conflicts.
AT ACC 15
Key clinical point: Elevated anxiety levels are much more common than depression in patients with adult congenital heart disease.
Major finding: Elevated levels of anxiety were found in 42% of ACHD patients; only 12% had elevated depression.
Data source: An outpatient adult congenital heart disease clinic in which 134 patients attending were assessed for anxiety, depression, and quality of life using validated instruments.
Disclosures: This study was supported by a research grant from Big Hearts in Little Bodies. The presenter reported having no financial conflicts.
Costs a wash between CTA and functional chest pain testing
SAN DIEGO– After the first 90 days, there is very little difference in costs out to 3 years between CT angiography and functional testing in the initial evaluation of stable patients with new chest pain, an economic substudy of the PROMISE trial showed.
“CT coronary angiography may not be the ‘holy grail’ of diagnostic tests that we once envisioned, but its more liberal use based on the results of PROMISE may improve some aspects of patient care and I don’t think will be a major new economic burden on the health care system,” study author Dr. Daniel B. Mark said at the annual meeting of the American College of Cardiology.
The PROMISE trial, also presented at the ACA meeting, found no advantage with respect to hard clinical outcomes between the two initial testing strategies, but CTA led to fewer catheterizations showing no obstructive disease and a twofold increase in revascularizations.
The economic analysis involved initial test technical fees, hospital-based facility costs, and physician professional fees for testing and hospital services for 96% of the 9,649 patients in the study.
The estimated cost of CT angiography, including physician fees and technical fees, was $404, compared with $174 for exercise treadmill testing, $501 for echocardiography with pharmacologic stress, $514 for echo with exercise stress, $946 for nuclear testing with exercise stress, and $1,132 for nuclear testing with pharmacologic stress, said Dr. Mark, director of outcomes research at Duke Clinical Research Institute, Durham, N.C.
The trend toward higher costs with CT angiography was driven largely by more revascularizations, with very in little added costs occurring after 90 days, he noted.
An analysis that factored in what was done to patients after their initial test showed CT angiography was more expensive than functional testing by an average of $279 at 90 days, $358 at 1 year, $388 at 2 years, and $694 at 3 years. The 95% confidence intervals were wide, so none of the differences were statistically significant, he said.
A number of patients underwent very expensive noncardiovascular procedures in the third year that bumped the average cost up in the CT arm, “but we don’t think this has anything to do with the strategies to which they were randomized,” Dr. Mark explained.
Caveats to the analysis include use of an external data source (Premier Research Database) for initial diagnostic testing costs, outpatient medications were not counted, and significant deviations in testing costs by centers that might alter cost results of the two strategies. Quality of life and employment status are also still being analyzed, Dr. Mark said.
A cost-effectiveness analysis was not performed because CT angiography outcomes were not superior as hypothesized in PROMISE.
The study was funded by the National Institutes of Health. Dr. Mark disclosed consulting for Milestone, Medtronic, CardioDx, and St. Jude Medical and research grants from the NIH, Eli Lilly, AstraZeneca, Gilead, AGA Medical, and Bristol-Myers Squibb.
SAN DIEGO– After the first 90 days, there is very little difference in costs out to 3 years between CT angiography and functional testing in the initial evaluation of stable patients with new chest pain, an economic substudy of the PROMISE trial showed.
“CT coronary angiography may not be the ‘holy grail’ of diagnostic tests that we once envisioned, but its more liberal use based on the results of PROMISE may improve some aspects of patient care and I don’t think will be a major new economic burden on the health care system,” study author Dr. Daniel B. Mark said at the annual meeting of the American College of Cardiology.
The PROMISE trial, also presented at the ACA meeting, found no advantage with respect to hard clinical outcomes between the two initial testing strategies, but CTA led to fewer catheterizations showing no obstructive disease and a twofold increase in revascularizations.
The economic analysis involved initial test technical fees, hospital-based facility costs, and physician professional fees for testing and hospital services for 96% of the 9,649 patients in the study.
The estimated cost of CT angiography, including physician fees and technical fees, was $404, compared with $174 for exercise treadmill testing, $501 for echocardiography with pharmacologic stress, $514 for echo with exercise stress, $946 for nuclear testing with exercise stress, and $1,132 for nuclear testing with pharmacologic stress, said Dr. Mark, director of outcomes research at Duke Clinical Research Institute, Durham, N.C.
The trend toward higher costs with CT angiography was driven largely by more revascularizations, with very in little added costs occurring after 90 days, he noted.
An analysis that factored in what was done to patients after their initial test showed CT angiography was more expensive than functional testing by an average of $279 at 90 days, $358 at 1 year, $388 at 2 years, and $694 at 3 years. The 95% confidence intervals were wide, so none of the differences were statistically significant, he said.
A number of patients underwent very expensive noncardiovascular procedures in the third year that bumped the average cost up in the CT arm, “but we don’t think this has anything to do with the strategies to which they were randomized,” Dr. Mark explained.
Caveats to the analysis include use of an external data source (Premier Research Database) for initial diagnostic testing costs, outpatient medications were not counted, and significant deviations in testing costs by centers that might alter cost results of the two strategies. Quality of life and employment status are also still being analyzed, Dr. Mark said.
A cost-effectiveness analysis was not performed because CT angiography outcomes were not superior as hypothesized in PROMISE.
The study was funded by the National Institutes of Health. Dr. Mark disclosed consulting for Milestone, Medtronic, CardioDx, and St. Jude Medical and research grants from the NIH, Eli Lilly, AstraZeneca, Gilead, AGA Medical, and Bristol-Myers Squibb.
SAN DIEGO– After the first 90 days, there is very little difference in costs out to 3 years between CT angiography and functional testing in the initial evaluation of stable patients with new chest pain, an economic substudy of the PROMISE trial showed.
“CT coronary angiography may not be the ‘holy grail’ of diagnostic tests that we once envisioned, but its more liberal use based on the results of PROMISE may improve some aspects of patient care and I don’t think will be a major new economic burden on the health care system,” study author Dr. Daniel B. Mark said at the annual meeting of the American College of Cardiology.
The PROMISE trial, also presented at the ACA meeting, found no advantage with respect to hard clinical outcomes between the two initial testing strategies, but CTA led to fewer catheterizations showing no obstructive disease and a twofold increase in revascularizations.
The economic analysis involved initial test technical fees, hospital-based facility costs, and physician professional fees for testing and hospital services for 96% of the 9,649 patients in the study.
The estimated cost of CT angiography, including physician fees and technical fees, was $404, compared with $174 for exercise treadmill testing, $501 for echocardiography with pharmacologic stress, $514 for echo with exercise stress, $946 for nuclear testing with exercise stress, and $1,132 for nuclear testing with pharmacologic stress, said Dr. Mark, director of outcomes research at Duke Clinical Research Institute, Durham, N.C.
The trend toward higher costs with CT angiography was driven largely by more revascularizations, with very in little added costs occurring after 90 days, he noted.
An analysis that factored in what was done to patients after their initial test showed CT angiography was more expensive than functional testing by an average of $279 at 90 days, $358 at 1 year, $388 at 2 years, and $694 at 3 years. The 95% confidence intervals were wide, so none of the differences were statistically significant, he said.
A number of patients underwent very expensive noncardiovascular procedures in the third year that bumped the average cost up in the CT arm, “but we don’t think this has anything to do with the strategies to which they were randomized,” Dr. Mark explained.
Caveats to the analysis include use of an external data source (Premier Research Database) for initial diagnostic testing costs, outpatient medications were not counted, and significant deviations in testing costs by centers that might alter cost results of the two strategies. Quality of life and employment status are also still being analyzed, Dr. Mark said.
A cost-effectiveness analysis was not performed because CT angiography outcomes were not superior as hypothesized in PROMISE.
The study was funded by the National Institutes of Health. Dr. Mark disclosed consulting for Milestone, Medtronic, CardioDx, and St. Jude Medical and research grants from the NIH, Eli Lilly, AstraZeneca, Gilead, AGA Medical, and Bristol-Myers Squibb.
AT ACC 2015
Evidence builds for complete revascularization in STEMI
SAN DIEGO– Complete revascularization of multivessel disease in patients hospitalized for ST-segment elevation MI improves long-term outcomes, although PCI of the culprit lesion only remains an option for some, the DANAMI3-PRIMULTI trial results suggest.
At 1 year, fractional flow reserve–guided complete revascularization significantly reduced the risk of all-cause death, nonfatal MI, and repeat revascularization, from 22% with infarct-only percutaneous coronary intervention (PCI) to 13%.
The reduction in the primary composite endpoint, however, was driven only by the need for fewer repeat revascularizations of non–infarct-related artery (IRA) lesions and not by hard endpoints.
“Therefore, although complete revascularization should be recommended, any condition that makes complex PCI unattractive may support a more conservative strategy of IRA PCI only,” principal investigator Thomas Engstrøm said at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.
Current guidelines support IRA-only PCI, although two contemporary studies – PRAMI and CvLPRIT – suggest that a preventive strategy of revascularization of all lesions in the coronary arteries improves outcomes, he noted.
DANAMI3-PRIMULTI (Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: Primary PCI in Multivessel Disease) is the largest trial to date to examine this issue.
Investigators at two centers randomized 2,239 patients within 12 hours of STEMI to conventional primary PCI, ischemic postconditioning, or deferred stenting. Among 2,212 patients who had successful infarct-related artery PCI, 627 had multivessel disease and were further randomized to IRA PCI only or fractional flow reserve-guided complete revascularization. Multivessel disease was defined as greater than 50% stenosis in a non-IRA artery greater than 2 mm suitable for PCI.
Nonfatal MI occurred in 5% of patients in both groups, and all-cause death occurred in 4% of IRA-only patients and 5% of complete revascularization patients, reported Dr. Engstrøm, consultant cardiologist, Rigshospitalet, University of Copenhagen.
Ischemia-driven revascularizations were significantly more common in the IRA-only group, at 17%, compared with 5% in complete revascularization group, a significant difference. Notably, 40% of these repeat revascularizations were urgent on the basis of unstable angina, he said.
Panelist Sunil V. Rao, from Duke University in Durham, N.C., asked whether the knowledge that residual disease was left behind in half of the patients in the unblinded trial could potentially bias against the IRA-only arm.
Dr. Engstrøm acknowledged that “there may be a bias when the patients leave the hospital and know they have stenoses that are untreated,” but said great care was taken in the design of the trial because “we wanted to stress quite precisely the wording of the guidelines, which state that repeat revascularization could be either due to subjective or objective ischemia and to answer this question.”
DANAMI3-PRIMULTI’s modest patient population sets the stage for larger, more conclusive studies, but in the meantime will have an interesting impact on the U.S. guideline recommendation, currently a class III recommendation and suggestive of harm for treating additional lesions in the setting of acute MI, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said.
Dr. Kandzari echoed concerns that awareness of residual disease may have influenced the likelihood of repeat revascularizations, but also complimented the investigators on a thoughtful trial design that selected lesions based on clinically significant criteria and allowed non-infarct–related arteries to be treated in a staged fashion rather than mandating treatment at the time of PCI.
There was only one death between the index procedure and the additional PCI and this was caused by a cardiac rupture, and thus merely a result of the disease itself and not the staged approach, Dr. Engstrøm said in an interview.
“Of course, you can argue that full revascularization at the time of the index lesion may support even the IRA territory resulting in smaller final infarcts,” he added. “We find this, however, unlikely since both groups ended up with quite small infarct sequelae: LVEF 50% in both groups.”
Panelist Theodore A. Bass, chief of cardiology at the University of Florida in Jacksonville, said the trial “further confirms emerging data that in the same setting, or at least the same hospitalization, more aggressive treatment may be warranted in certain patients.”
“Our data support that complete revascularization can be done without harm and with a very good outcome,” Dr. Engstrøm said. “So you might argue: Why wait for the readmission either in the case of stable angina or in the indication of unstable angina with a need for urgent PCI?”
Dr. Engstrøm reported having no financial disclosures. Dr. Rao reported consulting fees/honoraria from Terumo Medical and the Medicines Company and research grants from Bellerophon Therapeutics. Dr. Kandzari reported consultant fees/honoraria from Boston Scientific, Medtronic, Micell Technologies, and Thoratec. Dr. Bass reported consulting fees/honoraria from Merck.
SAN DIEGO– Complete revascularization of multivessel disease in patients hospitalized for ST-segment elevation MI improves long-term outcomes, although PCI of the culprit lesion only remains an option for some, the DANAMI3-PRIMULTI trial results suggest.
At 1 year, fractional flow reserve–guided complete revascularization significantly reduced the risk of all-cause death, nonfatal MI, and repeat revascularization, from 22% with infarct-only percutaneous coronary intervention (PCI) to 13%.
The reduction in the primary composite endpoint, however, was driven only by the need for fewer repeat revascularizations of non–infarct-related artery (IRA) lesions and not by hard endpoints.
“Therefore, although complete revascularization should be recommended, any condition that makes complex PCI unattractive may support a more conservative strategy of IRA PCI only,” principal investigator Thomas Engstrøm said at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.
Current guidelines support IRA-only PCI, although two contemporary studies – PRAMI and CvLPRIT – suggest that a preventive strategy of revascularization of all lesions in the coronary arteries improves outcomes, he noted.
DANAMI3-PRIMULTI (Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: Primary PCI in Multivessel Disease) is the largest trial to date to examine this issue.
Investigators at two centers randomized 2,239 patients within 12 hours of STEMI to conventional primary PCI, ischemic postconditioning, or deferred stenting. Among 2,212 patients who had successful infarct-related artery PCI, 627 had multivessel disease and were further randomized to IRA PCI only or fractional flow reserve-guided complete revascularization. Multivessel disease was defined as greater than 50% stenosis in a non-IRA artery greater than 2 mm suitable for PCI.
Nonfatal MI occurred in 5% of patients in both groups, and all-cause death occurred in 4% of IRA-only patients and 5% of complete revascularization patients, reported Dr. Engstrøm, consultant cardiologist, Rigshospitalet, University of Copenhagen.
Ischemia-driven revascularizations were significantly more common in the IRA-only group, at 17%, compared with 5% in complete revascularization group, a significant difference. Notably, 40% of these repeat revascularizations were urgent on the basis of unstable angina, he said.
Panelist Sunil V. Rao, from Duke University in Durham, N.C., asked whether the knowledge that residual disease was left behind in half of the patients in the unblinded trial could potentially bias against the IRA-only arm.
Dr. Engstrøm acknowledged that “there may be a bias when the patients leave the hospital and know they have stenoses that are untreated,” but said great care was taken in the design of the trial because “we wanted to stress quite precisely the wording of the guidelines, which state that repeat revascularization could be either due to subjective or objective ischemia and to answer this question.”
DANAMI3-PRIMULTI’s modest patient population sets the stage for larger, more conclusive studies, but in the meantime will have an interesting impact on the U.S. guideline recommendation, currently a class III recommendation and suggestive of harm for treating additional lesions in the setting of acute MI, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said.
Dr. Kandzari echoed concerns that awareness of residual disease may have influenced the likelihood of repeat revascularizations, but also complimented the investigators on a thoughtful trial design that selected lesions based on clinically significant criteria and allowed non-infarct–related arteries to be treated in a staged fashion rather than mandating treatment at the time of PCI.
There was only one death between the index procedure and the additional PCI and this was caused by a cardiac rupture, and thus merely a result of the disease itself and not the staged approach, Dr. Engstrøm said in an interview.
“Of course, you can argue that full revascularization at the time of the index lesion may support even the IRA territory resulting in smaller final infarcts,” he added. “We find this, however, unlikely since both groups ended up with quite small infarct sequelae: LVEF 50% in both groups.”
Panelist Theodore A. Bass, chief of cardiology at the University of Florida in Jacksonville, said the trial “further confirms emerging data that in the same setting, or at least the same hospitalization, more aggressive treatment may be warranted in certain patients.”
“Our data support that complete revascularization can be done without harm and with a very good outcome,” Dr. Engstrøm said. “So you might argue: Why wait for the readmission either in the case of stable angina or in the indication of unstable angina with a need for urgent PCI?”
Dr. Engstrøm reported having no financial disclosures. Dr. Rao reported consulting fees/honoraria from Terumo Medical and the Medicines Company and research grants from Bellerophon Therapeutics. Dr. Kandzari reported consultant fees/honoraria from Boston Scientific, Medtronic, Micell Technologies, and Thoratec. Dr. Bass reported consulting fees/honoraria from Merck.
SAN DIEGO– Complete revascularization of multivessel disease in patients hospitalized for ST-segment elevation MI improves long-term outcomes, although PCI of the culprit lesion only remains an option for some, the DANAMI3-PRIMULTI trial results suggest.
At 1 year, fractional flow reserve–guided complete revascularization significantly reduced the risk of all-cause death, nonfatal MI, and repeat revascularization, from 22% with infarct-only percutaneous coronary intervention (PCI) to 13%.
The reduction in the primary composite endpoint, however, was driven only by the need for fewer repeat revascularizations of non–infarct-related artery (IRA) lesions and not by hard endpoints.
“Therefore, although complete revascularization should be recommended, any condition that makes complex PCI unattractive may support a more conservative strategy of IRA PCI only,” principal investigator Thomas Engstrøm said at the American College of Cardiology/Cardiovascular Research Foundation Innovation in Intervention Summit.
Current guidelines support IRA-only PCI, although two contemporary studies – PRAMI and CvLPRIT – suggest that a preventive strategy of revascularization of all lesions in the coronary arteries improves outcomes, he noted.
DANAMI3-PRIMULTI (Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: Primary PCI in Multivessel Disease) is the largest trial to date to examine this issue.
Investigators at two centers randomized 2,239 patients within 12 hours of STEMI to conventional primary PCI, ischemic postconditioning, or deferred stenting. Among 2,212 patients who had successful infarct-related artery PCI, 627 had multivessel disease and were further randomized to IRA PCI only or fractional flow reserve-guided complete revascularization. Multivessel disease was defined as greater than 50% stenosis in a non-IRA artery greater than 2 mm suitable for PCI.
Nonfatal MI occurred in 5% of patients in both groups, and all-cause death occurred in 4% of IRA-only patients and 5% of complete revascularization patients, reported Dr. Engstrøm, consultant cardiologist, Rigshospitalet, University of Copenhagen.
Ischemia-driven revascularizations were significantly more common in the IRA-only group, at 17%, compared with 5% in complete revascularization group, a significant difference. Notably, 40% of these repeat revascularizations were urgent on the basis of unstable angina, he said.
Panelist Sunil V. Rao, from Duke University in Durham, N.C., asked whether the knowledge that residual disease was left behind in half of the patients in the unblinded trial could potentially bias against the IRA-only arm.
Dr. Engstrøm acknowledged that “there may be a bias when the patients leave the hospital and know they have stenoses that are untreated,” but said great care was taken in the design of the trial because “we wanted to stress quite precisely the wording of the guidelines, which state that repeat revascularization could be either due to subjective or objective ischemia and to answer this question.”
DANAMI3-PRIMULTI’s modest patient population sets the stage for larger, more conclusive studies, but in the meantime will have an interesting impact on the U.S. guideline recommendation, currently a class III recommendation and suggestive of harm for treating additional lesions in the setting of acute MI, Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said.
Dr. Kandzari echoed concerns that awareness of residual disease may have influenced the likelihood of repeat revascularizations, but also complimented the investigators on a thoughtful trial design that selected lesions based on clinically significant criteria and allowed non-infarct–related arteries to be treated in a staged fashion rather than mandating treatment at the time of PCI.
There was only one death between the index procedure and the additional PCI and this was caused by a cardiac rupture, and thus merely a result of the disease itself and not the staged approach, Dr. Engstrøm said in an interview.
“Of course, you can argue that full revascularization at the time of the index lesion may support even the IRA territory resulting in smaller final infarcts,” he added. “We find this, however, unlikely since both groups ended up with quite small infarct sequelae: LVEF 50% in both groups.”
Panelist Theodore A. Bass, chief of cardiology at the University of Florida in Jacksonville, said the trial “further confirms emerging data that in the same setting, or at least the same hospitalization, more aggressive treatment may be warranted in certain patients.”
“Our data support that complete revascularization can be done without harm and with a very good outcome,” Dr. Engstrøm said. “So you might argue: Why wait for the readmission either in the case of stable angina or in the indication of unstable angina with a need for urgent PCI?”
Dr. Engstrøm reported having no financial disclosures. Dr. Rao reported consulting fees/honoraria from Terumo Medical and the Medicines Company and research grants from Bellerophon Therapeutics. Dr. Kandzari reported consultant fees/honoraria from Boston Scientific, Medtronic, Micell Technologies, and Thoratec. Dr. Bass reported consulting fees/honoraria from Merck.
AT ACC/CRFi2
Key clinical point: Complete revascularization of multivessel disease in patients with STEMI improved long-term outcomes, but may not be the optimal strategy for all.
Major finding: Complete revascularization reduced the risk of the primary endpoint from 22% with infarct-only PCI to 13%.
Data source: Randomized trial in 627 STEMI patients with multivessel disease.
Disclosures: The presenter had no financial disclosures.
Heart failure spurs 'cardiogenic diabetes'
SAN DIEGO – A series of reports in 2014 from several independent groups implicated heart failure as a trigger of type 2 diabetes; findings from several of the analyses also suggested that relief of congestion can result in rapid resolution of the diabetes.
The best way to manage new-onset diabetes in heart failure patients is to “minimize the congestion,” and to “try to achieve as good control of the heart failure as possible,” said Dr. Maya Guglin during a talk at the annual meeting of the American College of Cardiology, in which she laid out the evidence for this newly recognized form of type 2 diabetes. In a review she published in 2014, Dr. Guglin coined the term “cardiogenic diabetes” to describe the condition (Heart Fail. Rev. 2014;19:595-602).
Dr. Guglin traced the data trail for cardiogenic diabetes starting in a 2011 retrospective study of 15 patients with advanced heart failure who received a left ventricular assist device (LVAD) at Columbia University in New York (Eur. J. Heart Fail. 2011;13:195-9). These 15, about a third of the 43 total LVAD recipients at Columbia at the time, had been diagnosed with type 2 diabetes for an average of 6 years before receiving the device. Just before they got their device, their average hemoglobin A1c (HbA1c) level was 7.7%, and their average fasting plasma glucose level was 158 mg/dL. An average of 4 months later, their mean HbA1c had dropped to 6%, and their mean fasting glucose had fallen to 104 mg/dL. Six patients were completely off any diabetes medication. All this occurred while patients had a small increase in their body mass index, which Dr. Guglin attributed to their better physical condition and improved appetite.
Last year, another four reports appeared from four independent, U.S. heart failure groups with results that mirrored the Columbia experience. Dr. Guglin and her associates at the University of Kentucky, Lexington, reported their experience with 50 patients who received an LVAD during 2002-2012 and had type 2 diabetes just before they received a device, with an average HbA1c of 7.6%. Three months after LVAD placement, their average HbA1c had dropped to 5.7%, and 9-12 months after device placement, their average HbA1c level was 5.3% (ASAIO J. 2014;60:290-3). As in the Columbia series, these improvements in hyperglycemia occurred without any significant change in body mass index.
Dr. Guglin also cited similar findings in 50 LVAD patients treated at the University of Rochester (N.Y.)(ASAIO J. 2014;60:675-80), 28 LVAD patients at Penn State Medical College in Hershey, Pa. (Heart Surg. Forum 2014;17:E98-102), and 66 LVAD patients from the University of Illinois in Chicago (Eur. J. Heart Fail. 2014;16:1120-4). In these reports type 2 diabetes existed in roughly a quarter to a third of patients with advanced heart failure who qualified for an LVAD just prior to the time they received the device.
Dr. Guglin also cited two epidemiologic analyses with complementary findings on the risk for incident diabetes faced by heart failure patients. She and her associates reviewed data from 3,165 elderly Americans free from diabetes enrolled in the Cardiovascular Health Study. This cohort included 80 patients with heart failure and 3,085 without heart failure. During 3-4 years of follow-up, 6% of the heart failure patients developed new-onset diabetes, and an additional 10% developed new-onset impaired fasting glucose. In contrast, these incidence rates were 1.5% and 5%, respectively, in the enrollees without heart failure at baseline. In an analysis that controlled for several demographic and biomedical factors, heart failure linked with a statistically significant, 2.4-fold increased risk for the development of diabetes (Cardiology 2014;129:84-92).
And a Danish nationwide cohort study of more than 99,000 residents discharged from a first-time hospitalization for heart failure during 1997-2010 showed a statistically significant link between heart failure severity and an increased rate of development of incident diabetes using diuretic treatment dosage as a surrogate measure of heart failure severity (Diabetologia 2014;57:1595-1600).
The apparent impact of LVAD placement on type 2 diabetes contrasts with what happens in patients who receive a heart transplant, where this association has not been seen. Dr. Guglin suggested that may be because of the immunosuppression with steroids that heart transplant recipients receive, treatment that also prevents diabetes resolution, she said.
“It all boils down to congestion,” Dr. Guglin said in an interview. “Control congestion as much as possible to control the diabetes.”
Dr. Guglin had no relevant financial disclosures.
On Twitter @mitchelzoler
SAN DIEGO – A series of reports in 2014 from several independent groups implicated heart failure as a trigger of type 2 diabetes; findings from several of the analyses also suggested that relief of congestion can result in rapid resolution of the diabetes.
The best way to manage new-onset diabetes in heart failure patients is to “minimize the congestion,” and to “try to achieve as good control of the heart failure as possible,” said Dr. Maya Guglin during a talk at the annual meeting of the American College of Cardiology, in which she laid out the evidence for this newly recognized form of type 2 diabetes. In a review she published in 2014, Dr. Guglin coined the term “cardiogenic diabetes” to describe the condition (Heart Fail. Rev. 2014;19:595-602).
Dr. Guglin traced the data trail for cardiogenic diabetes starting in a 2011 retrospective study of 15 patients with advanced heart failure who received a left ventricular assist device (LVAD) at Columbia University in New York (Eur. J. Heart Fail. 2011;13:195-9). These 15, about a third of the 43 total LVAD recipients at Columbia at the time, had been diagnosed with type 2 diabetes for an average of 6 years before receiving the device. Just before they got their device, their average hemoglobin A1c (HbA1c) level was 7.7%, and their average fasting plasma glucose level was 158 mg/dL. An average of 4 months later, their mean HbA1c had dropped to 6%, and their mean fasting glucose had fallen to 104 mg/dL. Six patients were completely off any diabetes medication. All this occurred while patients had a small increase in their body mass index, which Dr. Guglin attributed to their better physical condition and improved appetite.
Last year, another four reports appeared from four independent, U.S. heart failure groups with results that mirrored the Columbia experience. Dr. Guglin and her associates at the University of Kentucky, Lexington, reported their experience with 50 patients who received an LVAD during 2002-2012 and had type 2 diabetes just before they received a device, with an average HbA1c of 7.6%. Three months after LVAD placement, their average HbA1c had dropped to 5.7%, and 9-12 months after device placement, their average HbA1c level was 5.3% (ASAIO J. 2014;60:290-3). As in the Columbia series, these improvements in hyperglycemia occurred without any significant change in body mass index.
Dr. Guglin also cited similar findings in 50 LVAD patients treated at the University of Rochester (N.Y.)(ASAIO J. 2014;60:675-80), 28 LVAD patients at Penn State Medical College in Hershey, Pa. (Heart Surg. Forum 2014;17:E98-102), and 66 LVAD patients from the University of Illinois in Chicago (Eur. J. Heart Fail. 2014;16:1120-4). In these reports type 2 diabetes existed in roughly a quarter to a third of patients with advanced heart failure who qualified for an LVAD just prior to the time they received the device.
Dr. Guglin also cited two epidemiologic analyses with complementary findings on the risk for incident diabetes faced by heart failure patients. She and her associates reviewed data from 3,165 elderly Americans free from diabetes enrolled in the Cardiovascular Health Study. This cohort included 80 patients with heart failure and 3,085 without heart failure. During 3-4 years of follow-up, 6% of the heart failure patients developed new-onset diabetes, and an additional 10% developed new-onset impaired fasting glucose. In contrast, these incidence rates were 1.5% and 5%, respectively, in the enrollees without heart failure at baseline. In an analysis that controlled for several demographic and biomedical factors, heart failure linked with a statistically significant, 2.4-fold increased risk for the development of diabetes (Cardiology 2014;129:84-92).
And a Danish nationwide cohort study of more than 99,000 residents discharged from a first-time hospitalization for heart failure during 1997-2010 showed a statistically significant link between heart failure severity and an increased rate of development of incident diabetes using diuretic treatment dosage as a surrogate measure of heart failure severity (Diabetologia 2014;57:1595-1600).
The apparent impact of LVAD placement on type 2 diabetes contrasts with what happens in patients who receive a heart transplant, where this association has not been seen. Dr. Guglin suggested that may be because of the immunosuppression with steroids that heart transplant recipients receive, treatment that also prevents diabetes resolution, she said.
“It all boils down to congestion,” Dr. Guglin said in an interview. “Control congestion as much as possible to control the diabetes.”
Dr. Guglin had no relevant financial disclosures.
On Twitter @mitchelzoler
SAN DIEGO – A series of reports in 2014 from several independent groups implicated heart failure as a trigger of type 2 diabetes; findings from several of the analyses also suggested that relief of congestion can result in rapid resolution of the diabetes.
The best way to manage new-onset diabetes in heart failure patients is to “minimize the congestion,” and to “try to achieve as good control of the heart failure as possible,” said Dr. Maya Guglin during a talk at the annual meeting of the American College of Cardiology, in which she laid out the evidence for this newly recognized form of type 2 diabetes. In a review she published in 2014, Dr. Guglin coined the term “cardiogenic diabetes” to describe the condition (Heart Fail. Rev. 2014;19:595-602).
Dr. Guglin traced the data trail for cardiogenic diabetes starting in a 2011 retrospective study of 15 patients with advanced heart failure who received a left ventricular assist device (LVAD) at Columbia University in New York (Eur. J. Heart Fail. 2011;13:195-9). These 15, about a third of the 43 total LVAD recipients at Columbia at the time, had been diagnosed with type 2 diabetes for an average of 6 years before receiving the device. Just before they got their device, their average hemoglobin A1c (HbA1c) level was 7.7%, and their average fasting plasma glucose level was 158 mg/dL. An average of 4 months later, their mean HbA1c had dropped to 6%, and their mean fasting glucose had fallen to 104 mg/dL. Six patients were completely off any diabetes medication. All this occurred while patients had a small increase in their body mass index, which Dr. Guglin attributed to their better physical condition and improved appetite.
Last year, another four reports appeared from four independent, U.S. heart failure groups with results that mirrored the Columbia experience. Dr. Guglin and her associates at the University of Kentucky, Lexington, reported their experience with 50 patients who received an LVAD during 2002-2012 and had type 2 diabetes just before they received a device, with an average HbA1c of 7.6%. Three months after LVAD placement, their average HbA1c had dropped to 5.7%, and 9-12 months after device placement, their average HbA1c level was 5.3% (ASAIO J. 2014;60:290-3). As in the Columbia series, these improvements in hyperglycemia occurred without any significant change in body mass index.
Dr. Guglin also cited similar findings in 50 LVAD patients treated at the University of Rochester (N.Y.)(ASAIO J. 2014;60:675-80), 28 LVAD patients at Penn State Medical College in Hershey, Pa. (Heart Surg. Forum 2014;17:E98-102), and 66 LVAD patients from the University of Illinois in Chicago (Eur. J. Heart Fail. 2014;16:1120-4). In these reports type 2 diabetes existed in roughly a quarter to a third of patients with advanced heart failure who qualified for an LVAD just prior to the time they received the device.
Dr. Guglin also cited two epidemiologic analyses with complementary findings on the risk for incident diabetes faced by heart failure patients. She and her associates reviewed data from 3,165 elderly Americans free from diabetes enrolled in the Cardiovascular Health Study. This cohort included 80 patients with heart failure and 3,085 without heart failure. During 3-4 years of follow-up, 6% of the heart failure patients developed new-onset diabetes, and an additional 10% developed new-onset impaired fasting glucose. In contrast, these incidence rates were 1.5% and 5%, respectively, in the enrollees without heart failure at baseline. In an analysis that controlled for several demographic and biomedical factors, heart failure linked with a statistically significant, 2.4-fold increased risk for the development of diabetes (Cardiology 2014;129:84-92).
And a Danish nationwide cohort study of more than 99,000 residents discharged from a first-time hospitalization for heart failure during 1997-2010 showed a statistically significant link between heart failure severity and an increased rate of development of incident diabetes using diuretic treatment dosage as a surrogate measure of heart failure severity (Diabetologia 2014;57:1595-1600).
The apparent impact of LVAD placement on type 2 diabetes contrasts with what happens in patients who receive a heart transplant, where this association has not been seen. Dr. Guglin suggested that may be because of the immunosuppression with steroids that heart transplant recipients receive, treatment that also prevents diabetes resolution, she said.
“It all boils down to congestion,” Dr. Guglin said in an interview. “Control congestion as much as possible to control the diabetes.”
Dr. Guglin had no relevant financial disclosures.
On Twitter @mitchelzoler
EXPERT ANALYSIS FROM ACC 2015
Thrombectomy fails to improve PCI outcomes, ups stroke risk
SAN DIEGO – Routine manual thrombectomy before percutaneous coronary intervention did not improve 180-day outcomes and was linked with an increased risk of stroke in patients with acute ST-segment elevation MI in the TOTAL trial.
Routine thrombectomy had no effect on the primary outcome of cardiovascular death, MI, cardiogenic shock, or New York Heart Association class IV heart failure, occurring in 6.9% of thrombectomy patients and 7% of PCI-only patients.
However, the study’s primary safety endpoint of stroke at 30 days doubled in patients undergoing routine thrombectomy before PCI to 33 events (0.7%), compared with those who had PCI with only bailout thrombectomy (16 events [0.3%]; P = .015).
The same pattern was observed with stroke or transient ischemic attack within 30 days (42 vs. 19 events; hazard ratio, 2.21; P = .003) and continued for stroke within 180 days (52 vs. 25 events; HR, 2.08; P = .002).
“The stroke findings are unexpected and we believe require confirmation in other datasets. A detailed case-by-case review is underway to help us understand the etiology and the relationship with the procedure,” lead author Dr. Sanjit S. Jolly said at the annual meeting of the American College of Cardiology.
Enthusiasm for manual thrombus aspiration was sparked by a survival benefit observed in the single-center, prospective TAPAS trial in ST-segment elevation MI patients (STEMI), and the procedure was widely adopted.
The more recent, multicenter TASTE trial, however, reported that routine thrombectomy before PCI failed to significantly reduce 30-day mortality in 7,244 STEMI patients, though there were trends toward reductions in stent thrombosis and hospitalization for recurrent MI.
TOTAL (Manual Aspiration Thrombectomy Plus PCI vs. PCI Alone in STEMI) randomly assigned 10,063 patients within 12 hours of STEMI symptoms to primary PCI either with upfront manual thrombectomy or only bailout thrombectomy if the PCI strategy failed.
The lack of significant differences between groups in the primary outcome was also true in all the components of the primary outcome. Furthermore, there was no effect on the primary outcome based on thrombotic burden, a question that remained unanswered after TASTE, Dr. Jolly reported. The TOTAL results were published online simultaneously with his report (N. Engl. J. Med. 2015 March 16 [doi:10.1056/NEJMoa1415098]).
“TOTAL and TASTE emphasize the need to conduct large randomized trials of common interventions, even when small trials appear positive,” Dr. Jolly said.
Discussant Dr. Steven Nissen, chair of cardiovascular medicine at Cleveland Clinic, described the routine use of thrombectomy as “a sad story about device regulation in the United States” in that the evidence level needed to get a medical device on the market is so far below that required for drug approval that patients undergo procedures without good randomized trial evidence to show they even work.
“We dodged a bullet recently with renal denervation when everyone thought it would work, and when you finally tested it, it didn’t,” Dr. Nissen said. “Let this be a lesson to us: We need to have more rigorous studies of medical devices before they get to market and get used in very large numbers of people.”
Currently, aspiration thrombectomy carries a IIa recommendation for use with PCI in the most recent ACC/American Heart Association guidelines for the management of patients with STEMI (J. Am. Coll. Cardiol. 2009;54:2205-41).
When asked whether the guidelines should change based on the TOTAL and TASTE results, Dr. Jolly said there should be a clear recommendation that routine thrombus aspiration should not be the appropriate approach, while the issue of bailout aspiration may be left to clinician judgment.
The finding of late strokes is difficult to understand and should be interpreted with caution because of the small number of strokes occurring between 30 and 180 days, he said. Detailed analysis of all strokes will be presented at a later meeting, but Rankin Scale scores show several strokes were “very debilitating.” There is a consistency in the data, as a meta-analysis of smaller trials also identified an increased stroke risk with adjunctive thrombectomy.
Discussant Dr. Gregg W. Stone, director of cardiovascular research and education at Columbia University Medical Center in New York, said a mechanism for periprocedural stroke with aspiration can be envisioned, but that understanding the risk of ongoing, late stroke is more difficult.
As for why thrombectomy didn’t work, “aspiration is incredibly inefficient, thromboemboli still occur before, during, and after aspiration, the timing of aspiration is often too late to benefit most patients,” and other mechanisms of myonecrosis may predominate, such as reperfusion injury, he observed.
Dr. Stone said the TOTAL results should change practice and that the guideline recommendation should be downgraded to IIb.
“There are some patients who have a very large thrombus burden who have trouble dealing with all that thrombus in the cath lab who might benefit, and it is impossible to design randomized trials for small sections and groups of patients,” he said. “I wouldn’t make it class III by any means, but I think it’ll take a long time for that reduction in use to actually transmit through clinical practice, because I must say interventional cardiologists love the idea of simply removing thrombus with a relatively easy-to-use device.”
Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said in an interview that TOTAL will make operators much more selective and cautious in their performance of thrombectomy until further insights into the stroke issue are available. Thrombectomy should be reserved for bailout instances and not as a front-line therapy, he said.
On the other hand, the stroke rate in the early phase was not significantly different between groups in an as-treated analysis, and an opportunity exists to investigate potential differences between stroke and nonstroke patients to determine whether other comorbidities rather than thrombectomy per se may account for the stroke signal, Dr. Kandzari observed.
TOTAL was funded by the Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic. Dr. Jolly disclosed receiving consulting fees and honoraria from AstraZeneca, speaking fees for St. Jude, and research grants from Medtronic. Dr. Nissen has received research support from and is a consultant/adviser to numerous pharmaceutical companies; all honoraria or consulting fees go directly to charity so that he receives neither income nor a tax deduction. Dr. Stone reported consulting honoraria from Guided Delivery Systems, Miracor, and Reva, and ownership interest or partnership in Arstasis, Caliber, VNT, Micardia, Biostar family funds, and Medfocus family funds. Dr. Kandzari reported research and grant support from Medtronic, Biotronic, Abbott Vascular, and Boston Scientific.
SAN DIEGO – Routine manual thrombectomy before percutaneous coronary intervention did not improve 180-day outcomes and was linked with an increased risk of stroke in patients with acute ST-segment elevation MI in the TOTAL trial.
Routine thrombectomy had no effect on the primary outcome of cardiovascular death, MI, cardiogenic shock, or New York Heart Association class IV heart failure, occurring in 6.9% of thrombectomy patients and 7% of PCI-only patients.
However, the study’s primary safety endpoint of stroke at 30 days doubled in patients undergoing routine thrombectomy before PCI to 33 events (0.7%), compared with those who had PCI with only bailout thrombectomy (16 events [0.3%]; P = .015).
The same pattern was observed with stroke or transient ischemic attack within 30 days (42 vs. 19 events; hazard ratio, 2.21; P = .003) and continued for stroke within 180 days (52 vs. 25 events; HR, 2.08; P = .002).
“The stroke findings are unexpected and we believe require confirmation in other datasets. A detailed case-by-case review is underway to help us understand the etiology and the relationship with the procedure,” lead author Dr. Sanjit S. Jolly said at the annual meeting of the American College of Cardiology.
Enthusiasm for manual thrombus aspiration was sparked by a survival benefit observed in the single-center, prospective TAPAS trial in ST-segment elevation MI patients (STEMI), and the procedure was widely adopted.
The more recent, multicenter TASTE trial, however, reported that routine thrombectomy before PCI failed to significantly reduce 30-day mortality in 7,244 STEMI patients, though there were trends toward reductions in stent thrombosis and hospitalization for recurrent MI.
TOTAL (Manual Aspiration Thrombectomy Plus PCI vs. PCI Alone in STEMI) randomly assigned 10,063 patients within 12 hours of STEMI symptoms to primary PCI either with upfront manual thrombectomy or only bailout thrombectomy if the PCI strategy failed.
The lack of significant differences between groups in the primary outcome was also true in all the components of the primary outcome. Furthermore, there was no effect on the primary outcome based on thrombotic burden, a question that remained unanswered after TASTE, Dr. Jolly reported. The TOTAL results were published online simultaneously with his report (N. Engl. J. Med. 2015 March 16 [doi:10.1056/NEJMoa1415098]).
“TOTAL and TASTE emphasize the need to conduct large randomized trials of common interventions, even when small trials appear positive,” Dr. Jolly said.
Discussant Dr. Steven Nissen, chair of cardiovascular medicine at Cleveland Clinic, described the routine use of thrombectomy as “a sad story about device regulation in the United States” in that the evidence level needed to get a medical device on the market is so far below that required for drug approval that patients undergo procedures without good randomized trial evidence to show they even work.
“We dodged a bullet recently with renal denervation when everyone thought it would work, and when you finally tested it, it didn’t,” Dr. Nissen said. “Let this be a lesson to us: We need to have more rigorous studies of medical devices before they get to market and get used in very large numbers of people.”
Currently, aspiration thrombectomy carries a IIa recommendation for use with PCI in the most recent ACC/American Heart Association guidelines for the management of patients with STEMI (J. Am. Coll. Cardiol. 2009;54:2205-41).
When asked whether the guidelines should change based on the TOTAL and TASTE results, Dr. Jolly said there should be a clear recommendation that routine thrombus aspiration should not be the appropriate approach, while the issue of bailout aspiration may be left to clinician judgment.
The finding of late strokes is difficult to understand and should be interpreted with caution because of the small number of strokes occurring between 30 and 180 days, he said. Detailed analysis of all strokes will be presented at a later meeting, but Rankin Scale scores show several strokes were “very debilitating.” There is a consistency in the data, as a meta-analysis of smaller trials also identified an increased stroke risk with adjunctive thrombectomy.
Discussant Dr. Gregg W. Stone, director of cardiovascular research and education at Columbia University Medical Center in New York, said a mechanism for periprocedural stroke with aspiration can be envisioned, but that understanding the risk of ongoing, late stroke is more difficult.
As for why thrombectomy didn’t work, “aspiration is incredibly inefficient, thromboemboli still occur before, during, and after aspiration, the timing of aspiration is often too late to benefit most patients,” and other mechanisms of myonecrosis may predominate, such as reperfusion injury, he observed.
Dr. Stone said the TOTAL results should change practice and that the guideline recommendation should be downgraded to IIb.
“There are some patients who have a very large thrombus burden who have trouble dealing with all that thrombus in the cath lab who might benefit, and it is impossible to design randomized trials for small sections and groups of patients,” he said. “I wouldn’t make it class III by any means, but I think it’ll take a long time for that reduction in use to actually transmit through clinical practice, because I must say interventional cardiologists love the idea of simply removing thrombus with a relatively easy-to-use device.”
Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said in an interview that TOTAL will make operators much more selective and cautious in their performance of thrombectomy until further insights into the stroke issue are available. Thrombectomy should be reserved for bailout instances and not as a front-line therapy, he said.
On the other hand, the stroke rate in the early phase was not significantly different between groups in an as-treated analysis, and an opportunity exists to investigate potential differences between stroke and nonstroke patients to determine whether other comorbidities rather than thrombectomy per se may account for the stroke signal, Dr. Kandzari observed.
TOTAL was funded by the Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic. Dr. Jolly disclosed receiving consulting fees and honoraria from AstraZeneca, speaking fees for St. Jude, and research grants from Medtronic. Dr. Nissen has received research support from and is a consultant/adviser to numerous pharmaceutical companies; all honoraria or consulting fees go directly to charity so that he receives neither income nor a tax deduction. Dr. Stone reported consulting honoraria from Guided Delivery Systems, Miracor, and Reva, and ownership interest or partnership in Arstasis, Caliber, VNT, Micardia, Biostar family funds, and Medfocus family funds. Dr. Kandzari reported research and grant support from Medtronic, Biotronic, Abbott Vascular, and Boston Scientific.
SAN DIEGO – Routine manual thrombectomy before percutaneous coronary intervention did not improve 180-day outcomes and was linked with an increased risk of stroke in patients with acute ST-segment elevation MI in the TOTAL trial.
Routine thrombectomy had no effect on the primary outcome of cardiovascular death, MI, cardiogenic shock, or New York Heart Association class IV heart failure, occurring in 6.9% of thrombectomy patients and 7% of PCI-only patients.
However, the study’s primary safety endpoint of stroke at 30 days doubled in patients undergoing routine thrombectomy before PCI to 33 events (0.7%), compared with those who had PCI with only bailout thrombectomy (16 events [0.3%]; P = .015).
The same pattern was observed with stroke or transient ischemic attack within 30 days (42 vs. 19 events; hazard ratio, 2.21; P = .003) and continued for stroke within 180 days (52 vs. 25 events; HR, 2.08; P = .002).
“The stroke findings are unexpected and we believe require confirmation in other datasets. A detailed case-by-case review is underway to help us understand the etiology and the relationship with the procedure,” lead author Dr. Sanjit S. Jolly said at the annual meeting of the American College of Cardiology.
Enthusiasm for manual thrombus aspiration was sparked by a survival benefit observed in the single-center, prospective TAPAS trial in ST-segment elevation MI patients (STEMI), and the procedure was widely adopted.
The more recent, multicenter TASTE trial, however, reported that routine thrombectomy before PCI failed to significantly reduce 30-day mortality in 7,244 STEMI patients, though there were trends toward reductions in stent thrombosis and hospitalization for recurrent MI.
TOTAL (Manual Aspiration Thrombectomy Plus PCI vs. PCI Alone in STEMI) randomly assigned 10,063 patients within 12 hours of STEMI symptoms to primary PCI either with upfront manual thrombectomy or only bailout thrombectomy if the PCI strategy failed.
The lack of significant differences between groups in the primary outcome was also true in all the components of the primary outcome. Furthermore, there was no effect on the primary outcome based on thrombotic burden, a question that remained unanswered after TASTE, Dr. Jolly reported. The TOTAL results were published online simultaneously with his report (N. Engl. J. Med. 2015 March 16 [doi:10.1056/NEJMoa1415098]).
“TOTAL and TASTE emphasize the need to conduct large randomized trials of common interventions, even when small trials appear positive,” Dr. Jolly said.
Discussant Dr. Steven Nissen, chair of cardiovascular medicine at Cleveland Clinic, described the routine use of thrombectomy as “a sad story about device regulation in the United States” in that the evidence level needed to get a medical device on the market is so far below that required for drug approval that patients undergo procedures without good randomized trial evidence to show they even work.
“We dodged a bullet recently with renal denervation when everyone thought it would work, and when you finally tested it, it didn’t,” Dr. Nissen said. “Let this be a lesson to us: We need to have more rigorous studies of medical devices before they get to market and get used in very large numbers of people.”
Currently, aspiration thrombectomy carries a IIa recommendation for use with PCI in the most recent ACC/American Heart Association guidelines for the management of patients with STEMI (J. Am. Coll. Cardiol. 2009;54:2205-41).
When asked whether the guidelines should change based on the TOTAL and TASTE results, Dr. Jolly said there should be a clear recommendation that routine thrombus aspiration should not be the appropriate approach, while the issue of bailout aspiration may be left to clinician judgment.
The finding of late strokes is difficult to understand and should be interpreted with caution because of the small number of strokes occurring between 30 and 180 days, he said. Detailed analysis of all strokes will be presented at a later meeting, but Rankin Scale scores show several strokes were “very debilitating.” There is a consistency in the data, as a meta-analysis of smaller trials also identified an increased stroke risk with adjunctive thrombectomy.
Discussant Dr. Gregg W. Stone, director of cardiovascular research and education at Columbia University Medical Center in New York, said a mechanism for periprocedural stroke with aspiration can be envisioned, but that understanding the risk of ongoing, late stroke is more difficult.
As for why thrombectomy didn’t work, “aspiration is incredibly inefficient, thromboemboli still occur before, during, and after aspiration, the timing of aspiration is often too late to benefit most patients,” and other mechanisms of myonecrosis may predominate, such as reperfusion injury, he observed.
Dr. Stone said the TOTAL results should change practice and that the guideline recommendation should be downgraded to IIb.
“There are some patients who have a very large thrombus burden who have trouble dealing with all that thrombus in the cath lab who might benefit, and it is impossible to design randomized trials for small sections and groups of patients,” he said. “I wouldn’t make it class III by any means, but I think it’ll take a long time for that reduction in use to actually transmit through clinical practice, because I must say interventional cardiologists love the idea of simply removing thrombus with a relatively easy-to-use device.”
Dr. David Kandzari, director of interventional cardiology at the Piedmont Heart Center in Atlanta, said in an interview that TOTAL will make operators much more selective and cautious in their performance of thrombectomy until further insights into the stroke issue are available. Thrombectomy should be reserved for bailout instances and not as a front-line therapy, he said.
On the other hand, the stroke rate in the early phase was not significantly different between groups in an as-treated analysis, and an opportunity exists to investigate potential differences between stroke and nonstroke patients to determine whether other comorbidities rather than thrombectomy per se may account for the stroke signal, Dr. Kandzari observed.
TOTAL was funded by the Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic. Dr. Jolly disclosed receiving consulting fees and honoraria from AstraZeneca, speaking fees for St. Jude, and research grants from Medtronic. Dr. Nissen has received research support from and is a consultant/adviser to numerous pharmaceutical companies; all honoraria or consulting fees go directly to charity so that he receives neither income nor a tax deduction. Dr. Stone reported consulting honoraria from Guided Delivery Systems, Miracor, and Reva, and ownership interest or partnership in Arstasis, Caliber, VNT, Micardia, Biostar family funds, and Medfocus family funds. Dr. Kandzari reported research and grant support from Medtronic, Biotronic, Abbott Vascular, and Boston Scientific.
AT ACC 2015
Key clinical point: Routine manual thrombectomy did not improve 180-day outcomes and increased the risk of stroke, compared with PCI alone.
Major finding: Thrombectomy plus PCI did not improve the primary outcome vs. PCI alone (6.9% vs. 7%) and doubled the 30-day stroke rate (0.7% vs. 0.3%).
Data source: Prospective study in 10,063 patients with STEMI.
Disclosures: TOTAL was funded by the Canadian Institutes of Health Research, Canadian Network and Centre for Trials Internationally, and Medtronic. Dr. Jolly disclosed receiving consulting fees and honoraria from AstraZeneca, speaking fees for St. Jude, and research grants from Medtronic.
Heart surgeons get serious about RCTs
SAN DIEGO – The days when cardiologists could look down their noses at cardiac surgeons as primitive when it comes to conducting high-quality clinical research have come and gone.
“Cardiologists have been much more sophisticated than we have in doing randomized controlled trials. But cardiac surgeons are finally making strong progress in conducting randomized clinical trials, an area we’re not typically known for,” Dr. Vinod H. Thourani asserted at the annual meeting of the American College of Cardiology.
Much of this progress can be credited to the relatively recent creation of the Cardiothoracic Surgical Trials Network (CSTN), funded by the U.S. National Institutions of Health and the Canadian Institutes of Health Research. This surgical network is carrying out cutting-edge RCTs that will change the practice of cardiology as well as heart surgery, said Dr. Thourani, professor of surgery and codirector of the Structural Heart and Valve Center at Emory University, Atlanta.
To illustrate the breadth of current research in cardiothoracic surgery, he presented thumbnail sketches of RCTs due to report findings as early as this spring and no later than the latter part of next year or early 2017. The trials he selected, some conducted by the CSTN and others with industry sponsorship, address the aortic valve, the mitral valve, postoperative atrial fibrillation, revascularization in patients with unprotected left main coronary artery disease, and advanced heart failure.
• Heart failure: Outcomes of the ENDURANCE destination trial are due to be presented this spring at the annual meeting of the International Society for Heart and Lung Transplantation in Nice, France. This study will compare 12-month outcomes of continuous-flow ventricular assist devices as destination therapy in advanced heart failure. In this HeartWare-sponsored study, 310 patients received the investigational HeartWare ventricular assist system and 155 controls were implanted with the FDA-approved HeartMate II device marketed by Thoratec.
• Atrial fibrillation: The Rate Control Versus Rhythm Control for Postoperative Atrial Fibrillation trial compares the two management strategies in patients with new-onset AF following cardiac surgery. This CSTN-conducted study, to be presented next year, looks at which treatment approach results in fewer days in the hospital, as well as heart rhythm at discharge and through 60 days of follow-up, economic costs, and the incidence of postoperative clinical events.
• Coronary artery disease: The EXCEL trial has randomized 2,600 patients with unprotected left main coronary artery disease to coronary artery bypass surgery or percutaneous intervention with a XIENCE everolimus-eluting stent. The primary outcome is the composite of all-cause mortality, acute MI, or stroke. First results of this Abbott Vascular–sponsored trial are due to be reported next year.“This is a study that will clearly be impactful for you,” Dr. Thourani observed.
• Aortic valve disease: Two major RCTs are looking at the impact of extending transcatheter aortic valve replacement (TAVR) to an intermediate-surgical-risk population of patients with symptomatic severe aortic stenosis. The PARTNER II trial compares transfemoral or transapical/transaortic TAVR with a SAPIEN XT valve to surgical aortic valve replacement in patients with a Society of Thoracic Surgeons mortality risk score of 4%-8%. The primary endpoint is all-cause mortality and disabling stroke at 2 years. Results of this Edwards Lifesciences–sponsored trial will be presented by early 2016.
The Medtronic-sponsored SURTAVI trial compares TAVR using the company’s CoreValve alone or with PCI if revascularization is indicated versus surgical aortic valve replacement alone or with coronary artery bypass grafting if revascularization is indicated. This is a randomized trial involving 2,500 intermediate-risk patients. Of note, the SURTAVI investigators have revised the study protocol to open the trial to patients who are age 75 years or older or have an STS score of 2%-10%, which really redefines the concept of intermediate risk, Dr. Thourani said. Results will be presented by early 2017.
• Mitral valve disease: The Evaluation of Outcomes Following Mitral Valve Repair/Replacement in Severe Chronic Ischemic Mitral Regurgitation trial, carried out by the CSTN, will present 2-year outcome data later this year or in early 2016. The 1-year results caused major consternation in the surgical world. The eye opener was that 33% of patients in the repair group had moderate or severe mitral regurgitation at 12 months, compared with just 2% in the replacement group (N. Engl. J. Med. 2014;370:23-32). Mitral valve repair has traditionally been by far the more popular strategy. If the 2-year results show a growing disparity in terms of rates of severe mitral regurgitation, that may change.
Another CSTN study, the Surgical Intervention in Moderate Ischemic Mitral Regurgitation trial, found no demonstrable clinical benefit in adding a mitral valve repair operation to CABG surgery at 1 year of follow-up. The incidence of moderate or severe mitral regurgitation was lower at 1 year with concomitant valve repair and CABG, but this was offset by more neurologic events, longer ICU and total hospital stays, and no differences in the degree of reverse remodeling, mortality, or quality of life (N. Engl. J. Med. 2014;371:2178-88).
“Two-year follow-up is ongoing. It really becomes very important that later this year or next year we’re going to have the results available for you to determine if the lower incidence of moderate or severe mitral regurgitation at 1 year translates into a net clinical benefit for patients undergoing CABG and mitral repair. This study has big implications for the practice of thoracic surgery and for how cardiologists refer patients,” according to Dr. Thourani.
The COAPT trial is randomizing patients with symptomatic functional mitral regurgitation and very high surgical risk to percutaneous catheter-based treatment with the MitraClip or to a standard-care control group. One-year outcomes will be presented in 2016, and follow-up out to 5 years is planned.
“You can see now that in cardiac surgery there’s a lot going on,” Dr. Thourani concluded. “It’s not only good for us, but it’s good for you. As a cardiovascular community, we need to work together more.”
He reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott Medical, Boston Scientific, Medtronic, and Sorin.
SAN DIEGO – The days when cardiologists could look down their noses at cardiac surgeons as primitive when it comes to conducting high-quality clinical research have come and gone.
“Cardiologists have been much more sophisticated than we have in doing randomized controlled trials. But cardiac surgeons are finally making strong progress in conducting randomized clinical trials, an area we’re not typically known for,” Dr. Vinod H. Thourani asserted at the annual meeting of the American College of Cardiology.
Much of this progress can be credited to the relatively recent creation of the Cardiothoracic Surgical Trials Network (CSTN), funded by the U.S. National Institutions of Health and the Canadian Institutes of Health Research. This surgical network is carrying out cutting-edge RCTs that will change the practice of cardiology as well as heart surgery, said Dr. Thourani, professor of surgery and codirector of the Structural Heart and Valve Center at Emory University, Atlanta.
To illustrate the breadth of current research in cardiothoracic surgery, he presented thumbnail sketches of RCTs due to report findings as early as this spring and no later than the latter part of next year or early 2017. The trials he selected, some conducted by the CSTN and others with industry sponsorship, address the aortic valve, the mitral valve, postoperative atrial fibrillation, revascularization in patients with unprotected left main coronary artery disease, and advanced heart failure.
• Heart failure: Outcomes of the ENDURANCE destination trial are due to be presented this spring at the annual meeting of the International Society for Heart and Lung Transplantation in Nice, France. This study will compare 12-month outcomes of continuous-flow ventricular assist devices as destination therapy in advanced heart failure. In this HeartWare-sponsored study, 310 patients received the investigational HeartWare ventricular assist system and 155 controls were implanted with the FDA-approved HeartMate II device marketed by Thoratec.
• Atrial fibrillation: The Rate Control Versus Rhythm Control for Postoperative Atrial Fibrillation trial compares the two management strategies in patients with new-onset AF following cardiac surgery. This CSTN-conducted study, to be presented next year, looks at which treatment approach results in fewer days in the hospital, as well as heart rhythm at discharge and through 60 days of follow-up, economic costs, and the incidence of postoperative clinical events.
• Coronary artery disease: The EXCEL trial has randomized 2,600 patients with unprotected left main coronary artery disease to coronary artery bypass surgery or percutaneous intervention with a XIENCE everolimus-eluting stent. The primary outcome is the composite of all-cause mortality, acute MI, or stroke. First results of this Abbott Vascular–sponsored trial are due to be reported next year.“This is a study that will clearly be impactful for you,” Dr. Thourani observed.
• Aortic valve disease: Two major RCTs are looking at the impact of extending transcatheter aortic valve replacement (TAVR) to an intermediate-surgical-risk population of patients with symptomatic severe aortic stenosis. The PARTNER II trial compares transfemoral or transapical/transaortic TAVR with a SAPIEN XT valve to surgical aortic valve replacement in patients with a Society of Thoracic Surgeons mortality risk score of 4%-8%. The primary endpoint is all-cause mortality and disabling stroke at 2 years. Results of this Edwards Lifesciences–sponsored trial will be presented by early 2016.
The Medtronic-sponsored SURTAVI trial compares TAVR using the company’s CoreValve alone or with PCI if revascularization is indicated versus surgical aortic valve replacement alone or with coronary artery bypass grafting if revascularization is indicated. This is a randomized trial involving 2,500 intermediate-risk patients. Of note, the SURTAVI investigators have revised the study protocol to open the trial to patients who are age 75 years or older or have an STS score of 2%-10%, which really redefines the concept of intermediate risk, Dr. Thourani said. Results will be presented by early 2017.
• Mitral valve disease: The Evaluation of Outcomes Following Mitral Valve Repair/Replacement in Severe Chronic Ischemic Mitral Regurgitation trial, carried out by the CSTN, will present 2-year outcome data later this year or in early 2016. The 1-year results caused major consternation in the surgical world. The eye opener was that 33% of patients in the repair group had moderate or severe mitral regurgitation at 12 months, compared with just 2% in the replacement group (N. Engl. J. Med. 2014;370:23-32). Mitral valve repair has traditionally been by far the more popular strategy. If the 2-year results show a growing disparity in terms of rates of severe mitral regurgitation, that may change.
Another CSTN study, the Surgical Intervention in Moderate Ischemic Mitral Regurgitation trial, found no demonstrable clinical benefit in adding a mitral valve repair operation to CABG surgery at 1 year of follow-up. The incidence of moderate or severe mitral regurgitation was lower at 1 year with concomitant valve repair and CABG, but this was offset by more neurologic events, longer ICU and total hospital stays, and no differences in the degree of reverse remodeling, mortality, or quality of life (N. Engl. J. Med. 2014;371:2178-88).
“Two-year follow-up is ongoing. It really becomes very important that later this year or next year we’re going to have the results available for you to determine if the lower incidence of moderate or severe mitral regurgitation at 1 year translates into a net clinical benefit for patients undergoing CABG and mitral repair. This study has big implications for the practice of thoracic surgery and for how cardiologists refer patients,” according to Dr. Thourani.
The COAPT trial is randomizing patients with symptomatic functional mitral regurgitation and very high surgical risk to percutaneous catheter-based treatment with the MitraClip or to a standard-care control group. One-year outcomes will be presented in 2016, and follow-up out to 5 years is planned.
“You can see now that in cardiac surgery there’s a lot going on,” Dr. Thourani concluded. “It’s not only good for us, but it’s good for you. As a cardiovascular community, we need to work together more.”
He reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott Medical, Boston Scientific, Medtronic, and Sorin.
SAN DIEGO – The days when cardiologists could look down their noses at cardiac surgeons as primitive when it comes to conducting high-quality clinical research have come and gone.
“Cardiologists have been much more sophisticated than we have in doing randomized controlled trials. But cardiac surgeons are finally making strong progress in conducting randomized clinical trials, an area we’re not typically known for,” Dr. Vinod H. Thourani asserted at the annual meeting of the American College of Cardiology.
Much of this progress can be credited to the relatively recent creation of the Cardiothoracic Surgical Trials Network (CSTN), funded by the U.S. National Institutions of Health and the Canadian Institutes of Health Research. This surgical network is carrying out cutting-edge RCTs that will change the practice of cardiology as well as heart surgery, said Dr. Thourani, professor of surgery and codirector of the Structural Heart and Valve Center at Emory University, Atlanta.
To illustrate the breadth of current research in cardiothoracic surgery, he presented thumbnail sketches of RCTs due to report findings as early as this spring and no later than the latter part of next year or early 2017. The trials he selected, some conducted by the CSTN and others with industry sponsorship, address the aortic valve, the mitral valve, postoperative atrial fibrillation, revascularization in patients with unprotected left main coronary artery disease, and advanced heart failure.
• Heart failure: Outcomes of the ENDURANCE destination trial are due to be presented this spring at the annual meeting of the International Society for Heart and Lung Transplantation in Nice, France. This study will compare 12-month outcomes of continuous-flow ventricular assist devices as destination therapy in advanced heart failure. In this HeartWare-sponsored study, 310 patients received the investigational HeartWare ventricular assist system and 155 controls were implanted with the FDA-approved HeartMate II device marketed by Thoratec.
• Atrial fibrillation: The Rate Control Versus Rhythm Control for Postoperative Atrial Fibrillation trial compares the two management strategies in patients with new-onset AF following cardiac surgery. This CSTN-conducted study, to be presented next year, looks at which treatment approach results in fewer days in the hospital, as well as heart rhythm at discharge and through 60 days of follow-up, economic costs, and the incidence of postoperative clinical events.
• Coronary artery disease: The EXCEL trial has randomized 2,600 patients with unprotected left main coronary artery disease to coronary artery bypass surgery or percutaneous intervention with a XIENCE everolimus-eluting stent. The primary outcome is the composite of all-cause mortality, acute MI, or stroke. First results of this Abbott Vascular–sponsored trial are due to be reported next year.“This is a study that will clearly be impactful for you,” Dr. Thourani observed.
• Aortic valve disease: Two major RCTs are looking at the impact of extending transcatheter aortic valve replacement (TAVR) to an intermediate-surgical-risk population of patients with symptomatic severe aortic stenosis. The PARTNER II trial compares transfemoral or transapical/transaortic TAVR with a SAPIEN XT valve to surgical aortic valve replacement in patients with a Society of Thoracic Surgeons mortality risk score of 4%-8%. The primary endpoint is all-cause mortality and disabling stroke at 2 years. Results of this Edwards Lifesciences–sponsored trial will be presented by early 2016.
The Medtronic-sponsored SURTAVI trial compares TAVR using the company’s CoreValve alone or with PCI if revascularization is indicated versus surgical aortic valve replacement alone or with coronary artery bypass grafting if revascularization is indicated. This is a randomized trial involving 2,500 intermediate-risk patients. Of note, the SURTAVI investigators have revised the study protocol to open the trial to patients who are age 75 years or older or have an STS score of 2%-10%, which really redefines the concept of intermediate risk, Dr. Thourani said. Results will be presented by early 2017.
• Mitral valve disease: The Evaluation of Outcomes Following Mitral Valve Repair/Replacement in Severe Chronic Ischemic Mitral Regurgitation trial, carried out by the CSTN, will present 2-year outcome data later this year or in early 2016. The 1-year results caused major consternation in the surgical world. The eye opener was that 33% of patients in the repair group had moderate or severe mitral regurgitation at 12 months, compared with just 2% in the replacement group (N. Engl. J. Med. 2014;370:23-32). Mitral valve repair has traditionally been by far the more popular strategy. If the 2-year results show a growing disparity in terms of rates of severe mitral regurgitation, that may change.
Another CSTN study, the Surgical Intervention in Moderate Ischemic Mitral Regurgitation trial, found no demonstrable clinical benefit in adding a mitral valve repair operation to CABG surgery at 1 year of follow-up. The incidence of moderate or severe mitral regurgitation was lower at 1 year with concomitant valve repair and CABG, but this was offset by more neurologic events, longer ICU and total hospital stays, and no differences in the degree of reverse remodeling, mortality, or quality of life (N. Engl. J. Med. 2014;371:2178-88).
“Two-year follow-up is ongoing. It really becomes very important that later this year or next year we’re going to have the results available for you to determine if the lower incidence of moderate or severe mitral regurgitation at 1 year translates into a net clinical benefit for patients undergoing CABG and mitral repair. This study has big implications for the practice of thoracic surgery and for how cardiologists refer patients,” according to Dr. Thourani.
The COAPT trial is randomizing patients with symptomatic functional mitral regurgitation and very high surgical risk to percutaneous catheter-based treatment with the MitraClip or to a standard-care control group. One-year outcomes will be presented in 2016, and follow-up out to 5 years is planned.
“You can see now that in cardiac surgery there’s a lot going on,” Dr. Thourani concluded. “It’s not only good for us, but it’s good for you. As a cardiovascular community, we need to work together more.”
He reported serving as a consultant to Edwards Lifesciences and St. Jude Medical and receiving research grants from Abbott Medical, Boston Scientific, Medtronic, and Sorin.
EXPERT ANALYSIS FROM ACC 15
Ventricular gel injections improve advanced heart failure
SAN DIEGO – Beefing up a sick left ventricle via a set of injections of an inert alginate hydrogel resulted in significantly improved functional capacity, compared with optimal medical therapy through 6 months of follow-up in patients with advanced heart failure in the randomized AUGMENT-HF trial.
Investigators also noted “an interesting and striking reduction” in hospitalizations for worsening heart failure in the group that received left ventricular (LV) augmentation with the material, known as Algisyl-LVR, Dr. Stefan D. Anker reported at the annual meeting of the American College of Cardiology.
Indeed, among 78 patients with advanced heart failure randomized to hydrogel injections plus optimal medical therapy or to optimal medical therapy alone, there were 14 hospitalizations for worsening heart failure in eight controls, compared with 5 hospitalizations in four patients in the LV augmentation group. The between-group difference is large, but the number of hospitalizations is still small. AUGMENT-HF will continue for 2 years of follow-up.
“This gives us hope for the future,” said Dr. Anker, professor of cardiology and cachexia research at Charité Medical School, Berlin.
In addition, based upon the favorable 6-month study results, planning is underway for a larger, pivotal phase III U.S. trial of Algisyl-LVR, classified as a medical device, to start later this year.
At present, surgeons implant the hydrogel through a minithoracotomy. The procedure involves 10-20 injections totaling 4-5 mL of the inert, permanent material, which is placed as a ring of beads along a circumferential line at the left ventricular midwall.
“We make the wall thicker and the cavity of the ventricle a little smaller, thereby reducing wall stress. We basically try to change the physics of the pump action of the heart to improve patient status and perhaps patient outcome,” Dr. Anker explained.
Surgeons say it’s an easily learned procedure. The surgical morbidity and mortality seen in AUGMENT-HF were deemed acceptable by investigators and the study sponsor, so this new therapy will initially be developed as a surgical procedure. But it’s certainly a treatment that lends itself to delivery by percutaneous catheter in the future, according to the cardiologist.
Study participants had moderate to severe heart failure, with an average LV ejection fraction of 25%. Most were New York Heart Association (NYHA) functional class III.
The primary study endpoint was change in peak oxygen uptake (VO2) at 6 months from a baseline of 12.2 mL/kg/min. The value improved to 13.5 mL/kg/min in the LV augmentation group, compared with 12.4 mL/kg/min in controls, a between-group difference that Dr. Anker characterized as clinically relevant. He noted that one of the study’s strengths was that each peak VO2 result was the average of two tests performed on the same occasion, a method that markedly improves test reproducibility.
Also, 6-minute walk distance improved in the LV augmentation group by a mean of 84.7 meters from a baseline 280 meters, while decreasing by 15.4 meters in controls.
“This is quite a positive result rarely seen with other therapies. For everybody involved, this was a very positive finding,” Dr. Anker said.
Among controls, NYHC class stayed steady over the course of 6 months while showing a 0.9-class improvement in the LV augmentation group.
Heart failure etiology – ischemic versus nonischemic – had no bearing on LV augmentation’s effectiveness. Baseline 6-minute walk distance did, though. Patients with a baseline walk distance of less than 287 meters experienced a much larger treatment effect: a mean 2.42 mL/kg/min greater improvement from baseline to 6 months with LV augmentation than in controls, as compared with a nonsignificant 0.4 mL/kg/min advantage among patients who covered more than 287 meters at baseline.
The mean procedure time was 80 minutes, with 190 minutes of anesthesia time. Patients spent an average of 2 days in the ICU.
Three deaths occurred in the surgical group within the first 30 days. Excluding the index hospitalization, there were 22 major adverse cardiovascular events in the control group and 9 in the LV augmentation group. Among these were three cardiovascular deaths in each study arm, for a total of six deaths through 6 months in the LV augmentation patients. However, with additional study follow-up beyond the 6 months presented at ACC 15, mortality has evened out in the two groups, according to Dr. Anker. Sustained ventricular tachycardia occurred in four controls and one patient who received LV augmentation. Several audience members expressed surprise at the low arrhythmia rate in the LV augmentation group, but Dr. Anker’s coinvestigator Dr. Douglas L. Mann explained that the implantation doesn’t create an isthmus, thus there is no nidus for arrhythmia formation.
“No arrhythmia signal has been seen. There is actually a reduction in both atrial and ventricular arrhythmias,” said Dr. Mann, professor of internal medicine and chief of the division of cardiovascular medicine at Washington University in St. Louis.
The AUGMENT-HF trial was sponsored by LoneStar Heart. Dr. Anker reported having no financial relationship with LoneStar, although he serves as a consultant to half a dozen other health care companies.
SAN DIEGO – Beefing up a sick left ventricle via a set of injections of an inert alginate hydrogel resulted in significantly improved functional capacity, compared with optimal medical therapy through 6 months of follow-up in patients with advanced heart failure in the randomized AUGMENT-HF trial.
Investigators also noted “an interesting and striking reduction” in hospitalizations for worsening heart failure in the group that received left ventricular (LV) augmentation with the material, known as Algisyl-LVR, Dr. Stefan D. Anker reported at the annual meeting of the American College of Cardiology.
Indeed, among 78 patients with advanced heart failure randomized to hydrogel injections plus optimal medical therapy or to optimal medical therapy alone, there were 14 hospitalizations for worsening heart failure in eight controls, compared with 5 hospitalizations in four patients in the LV augmentation group. The between-group difference is large, but the number of hospitalizations is still small. AUGMENT-HF will continue for 2 years of follow-up.
“This gives us hope for the future,” said Dr. Anker, professor of cardiology and cachexia research at Charité Medical School, Berlin.
In addition, based upon the favorable 6-month study results, planning is underway for a larger, pivotal phase III U.S. trial of Algisyl-LVR, classified as a medical device, to start later this year.
At present, surgeons implant the hydrogel through a minithoracotomy. The procedure involves 10-20 injections totaling 4-5 mL of the inert, permanent material, which is placed as a ring of beads along a circumferential line at the left ventricular midwall.
“We make the wall thicker and the cavity of the ventricle a little smaller, thereby reducing wall stress. We basically try to change the physics of the pump action of the heart to improve patient status and perhaps patient outcome,” Dr. Anker explained.
Surgeons say it’s an easily learned procedure. The surgical morbidity and mortality seen in AUGMENT-HF were deemed acceptable by investigators and the study sponsor, so this new therapy will initially be developed as a surgical procedure. But it’s certainly a treatment that lends itself to delivery by percutaneous catheter in the future, according to the cardiologist.
Study participants had moderate to severe heart failure, with an average LV ejection fraction of 25%. Most were New York Heart Association (NYHA) functional class III.
The primary study endpoint was change in peak oxygen uptake (VO2) at 6 months from a baseline of 12.2 mL/kg/min. The value improved to 13.5 mL/kg/min in the LV augmentation group, compared with 12.4 mL/kg/min in controls, a between-group difference that Dr. Anker characterized as clinically relevant. He noted that one of the study’s strengths was that each peak VO2 result was the average of two tests performed on the same occasion, a method that markedly improves test reproducibility.
Also, 6-minute walk distance improved in the LV augmentation group by a mean of 84.7 meters from a baseline 280 meters, while decreasing by 15.4 meters in controls.
“This is quite a positive result rarely seen with other therapies. For everybody involved, this was a very positive finding,” Dr. Anker said.
Among controls, NYHC class stayed steady over the course of 6 months while showing a 0.9-class improvement in the LV augmentation group.
Heart failure etiology – ischemic versus nonischemic – had no bearing on LV augmentation’s effectiveness. Baseline 6-minute walk distance did, though. Patients with a baseline walk distance of less than 287 meters experienced a much larger treatment effect: a mean 2.42 mL/kg/min greater improvement from baseline to 6 months with LV augmentation than in controls, as compared with a nonsignificant 0.4 mL/kg/min advantage among patients who covered more than 287 meters at baseline.
The mean procedure time was 80 minutes, with 190 minutes of anesthesia time. Patients spent an average of 2 days in the ICU.
Three deaths occurred in the surgical group within the first 30 days. Excluding the index hospitalization, there were 22 major adverse cardiovascular events in the control group and 9 in the LV augmentation group. Among these were three cardiovascular deaths in each study arm, for a total of six deaths through 6 months in the LV augmentation patients. However, with additional study follow-up beyond the 6 months presented at ACC 15, mortality has evened out in the two groups, according to Dr. Anker. Sustained ventricular tachycardia occurred in four controls and one patient who received LV augmentation. Several audience members expressed surprise at the low arrhythmia rate in the LV augmentation group, but Dr. Anker’s coinvestigator Dr. Douglas L. Mann explained that the implantation doesn’t create an isthmus, thus there is no nidus for arrhythmia formation.
“No arrhythmia signal has been seen. There is actually a reduction in both atrial and ventricular arrhythmias,” said Dr. Mann, professor of internal medicine and chief of the division of cardiovascular medicine at Washington University in St. Louis.
The AUGMENT-HF trial was sponsored by LoneStar Heart. Dr. Anker reported having no financial relationship with LoneStar, although he serves as a consultant to half a dozen other health care companies.
SAN DIEGO – Beefing up a sick left ventricle via a set of injections of an inert alginate hydrogel resulted in significantly improved functional capacity, compared with optimal medical therapy through 6 months of follow-up in patients with advanced heart failure in the randomized AUGMENT-HF trial.
Investigators also noted “an interesting and striking reduction” in hospitalizations for worsening heart failure in the group that received left ventricular (LV) augmentation with the material, known as Algisyl-LVR, Dr. Stefan D. Anker reported at the annual meeting of the American College of Cardiology.
Indeed, among 78 patients with advanced heart failure randomized to hydrogel injections plus optimal medical therapy or to optimal medical therapy alone, there were 14 hospitalizations for worsening heart failure in eight controls, compared with 5 hospitalizations in four patients in the LV augmentation group. The between-group difference is large, but the number of hospitalizations is still small. AUGMENT-HF will continue for 2 years of follow-up.
“This gives us hope for the future,” said Dr. Anker, professor of cardiology and cachexia research at Charité Medical School, Berlin.
In addition, based upon the favorable 6-month study results, planning is underway for a larger, pivotal phase III U.S. trial of Algisyl-LVR, classified as a medical device, to start later this year.
At present, surgeons implant the hydrogel through a minithoracotomy. The procedure involves 10-20 injections totaling 4-5 mL of the inert, permanent material, which is placed as a ring of beads along a circumferential line at the left ventricular midwall.
“We make the wall thicker and the cavity of the ventricle a little smaller, thereby reducing wall stress. We basically try to change the physics of the pump action of the heart to improve patient status and perhaps patient outcome,” Dr. Anker explained.
Surgeons say it’s an easily learned procedure. The surgical morbidity and mortality seen in AUGMENT-HF were deemed acceptable by investigators and the study sponsor, so this new therapy will initially be developed as a surgical procedure. But it’s certainly a treatment that lends itself to delivery by percutaneous catheter in the future, according to the cardiologist.
Study participants had moderate to severe heart failure, with an average LV ejection fraction of 25%. Most were New York Heart Association (NYHA) functional class III.
The primary study endpoint was change in peak oxygen uptake (VO2) at 6 months from a baseline of 12.2 mL/kg/min. The value improved to 13.5 mL/kg/min in the LV augmentation group, compared with 12.4 mL/kg/min in controls, a between-group difference that Dr. Anker characterized as clinically relevant. He noted that one of the study’s strengths was that each peak VO2 result was the average of two tests performed on the same occasion, a method that markedly improves test reproducibility.
Also, 6-minute walk distance improved in the LV augmentation group by a mean of 84.7 meters from a baseline 280 meters, while decreasing by 15.4 meters in controls.
“This is quite a positive result rarely seen with other therapies. For everybody involved, this was a very positive finding,” Dr. Anker said.
Among controls, NYHC class stayed steady over the course of 6 months while showing a 0.9-class improvement in the LV augmentation group.
Heart failure etiology – ischemic versus nonischemic – had no bearing on LV augmentation’s effectiveness. Baseline 6-minute walk distance did, though. Patients with a baseline walk distance of less than 287 meters experienced a much larger treatment effect: a mean 2.42 mL/kg/min greater improvement from baseline to 6 months with LV augmentation than in controls, as compared with a nonsignificant 0.4 mL/kg/min advantage among patients who covered more than 287 meters at baseline.
The mean procedure time was 80 minutes, with 190 minutes of anesthesia time. Patients spent an average of 2 days in the ICU.
Three deaths occurred in the surgical group within the first 30 days. Excluding the index hospitalization, there were 22 major adverse cardiovascular events in the control group and 9 in the LV augmentation group. Among these were three cardiovascular deaths in each study arm, for a total of six deaths through 6 months in the LV augmentation patients. However, with additional study follow-up beyond the 6 months presented at ACC 15, mortality has evened out in the two groups, according to Dr. Anker. Sustained ventricular tachycardia occurred in four controls and one patient who received LV augmentation. Several audience members expressed surprise at the low arrhythmia rate in the LV augmentation group, but Dr. Anker’s coinvestigator Dr. Douglas L. Mann explained that the implantation doesn’t create an isthmus, thus there is no nidus for arrhythmia formation.
“No arrhythmia signal has been seen. There is actually a reduction in both atrial and ventricular arrhythmias,” said Dr. Mann, professor of internal medicine and chief of the division of cardiovascular medicine at Washington University in St. Louis.
The AUGMENT-HF trial was sponsored by LoneStar Heart. Dr. Anker reported having no financial relationship with LoneStar, although he serves as a consultant to half a dozen other health care companies.
AT ACC 15
Key clinical point: Left ventricular augmentation achieved through injections of an inert hydrogel shows promise as a novel therapy for advanced heart failure.
Major finding: Mean peak VO2 improved over the course of 6 months from a baseline of 12.2 mL/kg/min to 13.5 mL/kg/min in patients on optimal medical therapy who underwent the left ventricular augmentation procedure, compared with a 6-month value of 12.4 mL/kg/min in controls on optimal medical therapy alone.
Data source: AUGMENT-HF, a randomized, prospective, 78-patient clinical trial conducted in five countries.
Disclosures: AUGMENT-HF was sponsored by LoneStar Heart. The presenter reported having no financial relationship with LoneStar, although he serves as a consultant to half a dozen other health care companies.
A look at top upcoming clinical trials in electrophysiology
SAN DIEGO – How to prevent sudden arrhythmic death in vulnerable but currently unprotected populations is being addressed by ongoing studies that variously evaluate a pharmacologic, an implanted device-based, or a wearable solution, according to Dr. Bruce D. Lindsay.
Dr. Lindsay, head of the cardiac electrophysiology and pacing section at the Cleveland Clinic, presented an overview of selected major ongoing clinical trials in electrophysiology at the annual meeting of the American College of Cardiology. He focused on five hot topics: prevention of sudden death, atrial fibrillation (AF) ablation, prevention of implantable device-related infections, device-based treatment of heart failure, and leadless pacing systems.
Preventing sudden death
Ongoing phase III trials are evaluating the safety, tolerability, and efficacy of an oral Gilead drug known for now as GS-6615. The drug, a selective late sodium current inhibitor, is designed to shorten the corrected QTc interval in patients with several forms of long QT syndrome.
A different approach is being studied in REFINE-ICD (Risk Estimation Following Infarction Noninvasive Evaluation – ICD Efficacy), a 1,400-subject trial recruiting patients who’ve had an acute MI within the previous year, have abnormal findings on 24-hour Holter monitoring, and have moderate left ventricular dysfunction as defined by an ejection fraction of 35%-50%. The trial will assess whether prophylactic placement of an implantable cardioverter-defibrillator (ICD) guided by noninvasive risk assessment based on heart rate turbulence and T-wave alternans analysis will reduce mortality in MI survivors.
“This is a group that’s at lower risk than current ICD recipients, but because it’s such a large group they account for a lot of sudden deaths,” the cardiologist said.
Another phase III trial currently recruiting participants is a 1,900-patient postmarketing study aimed at defining which patients benefit from using the LifeVest wearable defibrillator during the first 3 months following an acute MI resulting in ventricular dysfunction.
AF ablation
The most important ongoing study in this field, in Dr. Lindsay’s view, is CABANA (Catheter Ablation Versus Anti-Arrhythmic Drug Therapy for Atrial Fibrillation Trial). This National Institutes of Health–sponsored study is aimed at showing whether ablation is superior to rate or rhythm control drug therapy in terms of all-cause mortality, disabling stroke, serious bleeding, and/or cardiac arrest. Secondary endpoints include cost, quality of life, hospitalization rates, and the relationship of left atrial size to progression of AF and its contribution to morbidity and mortality.
A promising, innovative ablation strategy known as focal impulse and rotor ablation for paroxysmal AF is under evaluation in the German REAFFIRM (Randomized Evaluation of Atrial Fibrillation Treatment With Focal Impulse and Rotor Modulation Guided Procedures). A similar U.S. study known as FIRMAT-PAF (Focal Impulse and Rotor Modulation Ablation Trial for Treatment of Paroxysmal Atrial Fibrillation) had to be abandoned, however, because of its inability to recruit patients.
New ablation technologies are also being introduced. Three pivotal trials totaling roughly 1,500 patients are evaluating the Biosense Webster nMARQ multielectrode irrigated catheter for paroxysmal AF in the reMARQable trial; a Medtronic phased radiofrequency ablation catheter for persistent AF in the VICTORY AF study; and a CardioFocus endoscopic ablation catheter for paroxysmal AF.
Preventing cardiac implantable device infections
WRAP-IT (the World-Wide Randomized Antibiotic Envelope Infection Trial) is currently enrolling 7,000 patients at 225 sites. This is a Merck-sponsored randomized, prospective, single-blind postmarketing study examining the ability of a proprietary mesh envelope to reduce major infections and costs in the 12 months following device generator replacement, upgrade, or revision, or new implantation of a cardiac resynchronization device. The Tyrx mesh envelope releases minocycline and rifampin for at least 7 days, then eventually becomes fully absorbed.
“Device infection is a huge problem in our field,” Dr. Lindsay noted. “This envelope may have important implications at large, or it may prove to be especially useful in people at high risk for infection.”
Heart failure
Vagal nerve stimulation via an implantable system is one of the hottest areas in the field of heart failure, the electrophysiologist said. Two major trials are ongoing: the Sorin-sponsored VANGUARD (Vagal Nerve Stimulation: Safeguarding Heart Failure Patients) trial, and INNOVATE HF (Increase of Vagal Tone in CHF), sponsored by Biocontrol Medical.
Leadless pacing
St. Jude’s Nanostim and Medtronic’s Micra are very small leadless devices implanted in the right ventricular apex via minimally invasive techniques. Both devices are investigational in the United States, although the Nanostim is approved in Europe. Clinical interest is enormous because lead-related problems have always been the Achilles’ heel of pacemaker therapy. While the Nanostim and Micra can be utilized only for single right ventricular pacing in VVI or VVIR mode, Dr. Lindsay said further advances, including leadless dual-chamber sensing and pacing and biventricular pacing, are likely.
He reported serving as a consultant to Biosense Webster, Boston Scientific, and Medtronic.
SAN DIEGO – How to prevent sudden arrhythmic death in vulnerable but currently unprotected populations is being addressed by ongoing studies that variously evaluate a pharmacologic, an implanted device-based, or a wearable solution, according to Dr. Bruce D. Lindsay.
Dr. Lindsay, head of the cardiac electrophysiology and pacing section at the Cleveland Clinic, presented an overview of selected major ongoing clinical trials in electrophysiology at the annual meeting of the American College of Cardiology. He focused on five hot topics: prevention of sudden death, atrial fibrillation (AF) ablation, prevention of implantable device-related infections, device-based treatment of heart failure, and leadless pacing systems.
Preventing sudden death
Ongoing phase III trials are evaluating the safety, tolerability, and efficacy of an oral Gilead drug known for now as GS-6615. The drug, a selective late sodium current inhibitor, is designed to shorten the corrected QTc interval in patients with several forms of long QT syndrome.
A different approach is being studied in REFINE-ICD (Risk Estimation Following Infarction Noninvasive Evaluation – ICD Efficacy), a 1,400-subject trial recruiting patients who’ve had an acute MI within the previous year, have abnormal findings on 24-hour Holter monitoring, and have moderate left ventricular dysfunction as defined by an ejection fraction of 35%-50%. The trial will assess whether prophylactic placement of an implantable cardioverter-defibrillator (ICD) guided by noninvasive risk assessment based on heart rate turbulence and T-wave alternans analysis will reduce mortality in MI survivors.
“This is a group that’s at lower risk than current ICD recipients, but because it’s such a large group they account for a lot of sudden deaths,” the cardiologist said.
Another phase III trial currently recruiting participants is a 1,900-patient postmarketing study aimed at defining which patients benefit from using the LifeVest wearable defibrillator during the first 3 months following an acute MI resulting in ventricular dysfunction.
AF ablation
The most important ongoing study in this field, in Dr. Lindsay’s view, is CABANA (Catheter Ablation Versus Anti-Arrhythmic Drug Therapy for Atrial Fibrillation Trial). This National Institutes of Health–sponsored study is aimed at showing whether ablation is superior to rate or rhythm control drug therapy in terms of all-cause mortality, disabling stroke, serious bleeding, and/or cardiac arrest. Secondary endpoints include cost, quality of life, hospitalization rates, and the relationship of left atrial size to progression of AF and its contribution to morbidity and mortality.
A promising, innovative ablation strategy known as focal impulse and rotor ablation for paroxysmal AF is under evaluation in the German REAFFIRM (Randomized Evaluation of Atrial Fibrillation Treatment With Focal Impulse and Rotor Modulation Guided Procedures). A similar U.S. study known as FIRMAT-PAF (Focal Impulse and Rotor Modulation Ablation Trial for Treatment of Paroxysmal Atrial Fibrillation) had to be abandoned, however, because of its inability to recruit patients.
New ablation technologies are also being introduced. Three pivotal trials totaling roughly 1,500 patients are evaluating the Biosense Webster nMARQ multielectrode irrigated catheter for paroxysmal AF in the reMARQable trial; a Medtronic phased radiofrequency ablation catheter for persistent AF in the VICTORY AF study; and a CardioFocus endoscopic ablation catheter for paroxysmal AF.
Preventing cardiac implantable device infections
WRAP-IT (the World-Wide Randomized Antibiotic Envelope Infection Trial) is currently enrolling 7,000 patients at 225 sites. This is a Merck-sponsored randomized, prospective, single-blind postmarketing study examining the ability of a proprietary mesh envelope to reduce major infections and costs in the 12 months following device generator replacement, upgrade, or revision, or new implantation of a cardiac resynchronization device. The Tyrx mesh envelope releases minocycline and rifampin for at least 7 days, then eventually becomes fully absorbed.
“Device infection is a huge problem in our field,” Dr. Lindsay noted. “This envelope may have important implications at large, or it may prove to be especially useful in people at high risk for infection.”
Heart failure
Vagal nerve stimulation via an implantable system is one of the hottest areas in the field of heart failure, the electrophysiologist said. Two major trials are ongoing: the Sorin-sponsored VANGUARD (Vagal Nerve Stimulation: Safeguarding Heart Failure Patients) trial, and INNOVATE HF (Increase of Vagal Tone in CHF), sponsored by Biocontrol Medical.
Leadless pacing
St. Jude’s Nanostim and Medtronic’s Micra are very small leadless devices implanted in the right ventricular apex via minimally invasive techniques. Both devices are investigational in the United States, although the Nanostim is approved in Europe. Clinical interest is enormous because lead-related problems have always been the Achilles’ heel of pacemaker therapy. While the Nanostim and Micra can be utilized only for single right ventricular pacing in VVI or VVIR mode, Dr. Lindsay said further advances, including leadless dual-chamber sensing and pacing and biventricular pacing, are likely.
He reported serving as a consultant to Biosense Webster, Boston Scientific, and Medtronic.
SAN DIEGO – How to prevent sudden arrhythmic death in vulnerable but currently unprotected populations is being addressed by ongoing studies that variously evaluate a pharmacologic, an implanted device-based, or a wearable solution, according to Dr. Bruce D. Lindsay.
Dr. Lindsay, head of the cardiac electrophysiology and pacing section at the Cleveland Clinic, presented an overview of selected major ongoing clinical trials in electrophysiology at the annual meeting of the American College of Cardiology. He focused on five hot topics: prevention of sudden death, atrial fibrillation (AF) ablation, prevention of implantable device-related infections, device-based treatment of heart failure, and leadless pacing systems.
Preventing sudden death
Ongoing phase III trials are evaluating the safety, tolerability, and efficacy of an oral Gilead drug known for now as GS-6615. The drug, a selective late sodium current inhibitor, is designed to shorten the corrected QTc interval in patients with several forms of long QT syndrome.
A different approach is being studied in REFINE-ICD (Risk Estimation Following Infarction Noninvasive Evaluation – ICD Efficacy), a 1,400-subject trial recruiting patients who’ve had an acute MI within the previous year, have abnormal findings on 24-hour Holter monitoring, and have moderate left ventricular dysfunction as defined by an ejection fraction of 35%-50%. The trial will assess whether prophylactic placement of an implantable cardioverter-defibrillator (ICD) guided by noninvasive risk assessment based on heart rate turbulence and T-wave alternans analysis will reduce mortality in MI survivors.
“This is a group that’s at lower risk than current ICD recipients, but because it’s such a large group they account for a lot of sudden deaths,” the cardiologist said.
Another phase III trial currently recruiting participants is a 1,900-patient postmarketing study aimed at defining which patients benefit from using the LifeVest wearable defibrillator during the first 3 months following an acute MI resulting in ventricular dysfunction.
AF ablation
The most important ongoing study in this field, in Dr. Lindsay’s view, is CABANA (Catheter Ablation Versus Anti-Arrhythmic Drug Therapy for Atrial Fibrillation Trial). This National Institutes of Health–sponsored study is aimed at showing whether ablation is superior to rate or rhythm control drug therapy in terms of all-cause mortality, disabling stroke, serious bleeding, and/or cardiac arrest. Secondary endpoints include cost, quality of life, hospitalization rates, and the relationship of left atrial size to progression of AF and its contribution to morbidity and mortality.
A promising, innovative ablation strategy known as focal impulse and rotor ablation for paroxysmal AF is under evaluation in the German REAFFIRM (Randomized Evaluation of Atrial Fibrillation Treatment With Focal Impulse and Rotor Modulation Guided Procedures). A similar U.S. study known as FIRMAT-PAF (Focal Impulse and Rotor Modulation Ablation Trial for Treatment of Paroxysmal Atrial Fibrillation) had to be abandoned, however, because of its inability to recruit patients.
New ablation technologies are also being introduced. Three pivotal trials totaling roughly 1,500 patients are evaluating the Biosense Webster nMARQ multielectrode irrigated catheter for paroxysmal AF in the reMARQable trial; a Medtronic phased radiofrequency ablation catheter for persistent AF in the VICTORY AF study; and a CardioFocus endoscopic ablation catheter for paroxysmal AF.
Preventing cardiac implantable device infections
WRAP-IT (the World-Wide Randomized Antibiotic Envelope Infection Trial) is currently enrolling 7,000 patients at 225 sites. This is a Merck-sponsored randomized, prospective, single-blind postmarketing study examining the ability of a proprietary mesh envelope to reduce major infections and costs in the 12 months following device generator replacement, upgrade, or revision, or new implantation of a cardiac resynchronization device. The Tyrx mesh envelope releases minocycline and rifampin for at least 7 days, then eventually becomes fully absorbed.
“Device infection is a huge problem in our field,” Dr. Lindsay noted. “This envelope may have important implications at large, or it may prove to be especially useful in people at high risk for infection.”
Heart failure
Vagal nerve stimulation via an implantable system is one of the hottest areas in the field of heart failure, the electrophysiologist said. Two major trials are ongoing: the Sorin-sponsored VANGUARD (Vagal Nerve Stimulation: Safeguarding Heart Failure Patients) trial, and INNOVATE HF (Increase of Vagal Tone in CHF), sponsored by Biocontrol Medical.
Leadless pacing
St. Jude’s Nanostim and Medtronic’s Micra are very small leadless devices implanted in the right ventricular apex via minimally invasive techniques. Both devices are investigational in the United States, although the Nanostim is approved in Europe. Clinical interest is enormous because lead-related problems have always been the Achilles’ heel of pacemaker therapy. While the Nanostim and Micra can be utilized only for single right ventricular pacing in VVI or VVIR mode, Dr. Lindsay said further advances, including leadless dual-chamber sensing and pacing and biventricular pacing, are likely.
He reported serving as a consultant to Biosense Webster, Boston Scientific, and Medtronic.
EXPERT ANALYSIS FROM ACC 15
