User login
New Evidence That Plaque Buildup Shouldn’t Be Ignored
Subclinical disease detected on imaging predicts death, report investigators who show that plaque burden found on 3D vascular ultrasound and coronary artery calcium on CT were better predictors of death than traditional risk factors.
The work not only highlights the importance of early detection, but it also has clinical implications, said Valentin Fuster, MD, president of the Mount Sinai Fuster Heart Hospital in New York. “It’s going to change things,” he said. “What I believe is going to happen is that we will begin to evaluate people with risk factors at age 30 using imaging. Today, we evaluate people at age 50 using clinical practice guidelines.”
Fuster’s team developed 3D vascular ultrasound to assess plaque burden and applied it in a prospective cohort study known as BioImage. The researchers assessed 6102 patients in Chicago, Illinois, and Fort Lauderdale, Florida, using 3D vascular ultrasound of the carotid artery and another well-established modality — coronary artery calcium, determined by CT.
Participants had no cardiovascular symptoms, yet their plaque burden and calcium scores at the beginning of the study were significantly associated with death during the 15 years of follow-up, even after taking risk factors and medication into account. The results are published in the Journal of the American College of Cardiology.
“Now, there is no question that subclinical disease on imaging predicts mortality,” said Fuster.
David J. Maron, MD, a preventive cardiologist at the Stanford University School of Medicine in California, calls the finding “very important.”
“The presence of atherosclerosis is powerful knowledge to guide the intensity of therapy and to motivate patients and clinicians to treat it,” said Maron, who is the co-author of an accompanying editorial and was not involved in the study.
Predicting Risk Early
The research also showed that the risk for death increases if the burden of plaque in the carotid artery increases over time. Both plaque burden shown on 3D vascular ultrasound and coronary artery calcium on CT were better predictors of death than traditional risk factors.
Maron says recent studies of younger populations, such as Progression of Early Subclinical Atherosclerosis (PESA) and Coronary Artery Risk Development in Young Adults (CARDIA), show that “risk factors at a young age have much more impact on arterial disease than when we measure risk factors at older age.” The CARDIA study showed signs of atherosclerosis in patients as young as in their twenties. This paradigm shift to early detection will now be possible thanks to technological advances like 3D vascular ultrasound.
Maron said he agrees with screening earlier in life. “The risk of having an event is related to the plaque burden and the number of years that a patient has been exposed to that burden. The earlier in life we can identify the burden to slow, arrest, or even reverse the plaque, the better.”
Maron points out that the study looked at an older population and did not include information on cause of death. While a study of younger people and data on cardiac causes of death would be useful, he says the study’s conclusions remain significant.
3D Vascular Ultrasound vs Coronary Artery Calcium
While both imaging methods in the study predicted death better than cardiovascular risk factors alone, each option has advantages.
For coronary artery calcium, “there’s a huge amount of literature demonstrating the association with cardiovascular events, there’s a standardized scoring system, there are widespread facilities for computed tomography, and there is not a lot of variability in the measurement — it’s not dependent on the operator,” said Maron.
But there is one drawback. The scoring system –— the Agatston score — can paradoxically go up following aggressive lowering of low-density lipoprotein cholesterol. “Once coronary calcium is present, it is challenging to interpret a repeat scan because we don’t know if the increase in score is due to progression or increasing density of the calcium, which is a sign of healing,” said Maron.
Vascular ultrasound avoids this problem and can also identify early noncalcified plaques and monitor their progression before they would appear on CT. Furthermore, the imaging does not add to lifetime radiation dose, as CT does, Fuster said.
3D ultrasound technology will soon be available in an inexpensive, automated, and easy-to-use format, he explains. Fuster envisions a scenario in which a nurse in a low-income country, using a cell phone app, will be able to assess atherosclerosis in a patient’s femoral artery. “In less than 1 hour, we can predict disease much more rigorously than with risk factors alone,” he said. “I think this is very exciting.”
Progression Increases Risk
Finding any atherosclerosis means an increased risk for death, but a greater burden or amount of atherosclerosis increases that risk, said Fuster. Progression of atherosclerosis increases risk even further.
The study looked at changes in atherosclerosis burden on vascular ultrasound in a subset of 732 patients a median of 8.9 years after their first test. Those with progression had a higher risk for death than those with regression or no atherosclerosis. “Progression is much more significant in predicting mortality than atherosclerosis findings alone,” Fuster said.
Maron said this finding points to “two great values from noninvasive imaging of atherosclerosis.” Not only does imaging detect atherosclerosis, but it can also characterize the burden and any calcification. Further, it allows doctors to monitor the response to interventions such as lifestyle changes and medical therapy. “Serial imaging of plaque burden will really enhance the management of atherosclerosis,” said Maron. “If we discover that someone is progressing rapidly, we can intensify therapy.”
He says imaging results also provide needed motivation for both clinicians and patients to take action that would prevent the deaths that result from atherosclerosis.
A version of this article appeared on Medscape.com.
Subclinical disease detected on imaging predicts death, report investigators who show that plaque burden found on 3D vascular ultrasound and coronary artery calcium on CT were better predictors of death than traditional risk factors.
The work not only highlights the importance of early detection, but it also has clinical implications, said Valentin Fuster, MD, president of the Mount Sinai Fuster Heart Hospital in New York. “It’s going to change things,” he said. “What I believe is going to happen is that we will begin to evaluate people with risk factors at age 30 using imaging. Today, we evaluate people at age 50 using clinical practice guidelines.”
Fuster’s team developed 3D vascular ultrasound to assess plaque burden and applied it in a prospective cohort study known as BioImage. The researchers assessed 6102 patients in Chicago, Illinois, and Fort Lauderdale, Florida, using 3D vascular ultrasound of the carotid artery and another well-established modality — coronary artery calcium, determined by CT.
Participants had no cardiovascular symptoms, yet their plaque burden and calcium scores at the beginning of the study were significantly associated with death during the 15 years of follow-up, even after taking risk factors and medication into account. The results are published in the Journal of the American College of Cardiology.
“Now, there is no question that subclinical disease on imaging predicts mortality,” said Fuster.
David J. Maron, MD, a preventive cardiologist at the Stanford University School of Medicine in California, calls the finding “very important.”
“The presence of atherosclerosis is powerful knowledge to guide the intensity of therapy and to motivate patients and clinicians to treat it,” said Maron, who is the co-author of an accompanying editorial and was not involved in the study.
Predicting Risk Early
The research also showed that the risk for death increases if the burden of plaque in the carotid artery increases over time. Both plaque burden shown on 3D vascular ultrasound and coronary artery calcium on CT were better predictors of death than traditional risk factors.
Maron says recent studies of younger populations, such as Progression of Early Subclinical Atherosclerosis (PESA) and Coronary Artery Risk Development in Young Adults (CARDIA), show that “risk factors at a young age have much more impact on arterial disease than when we measure risk factors at older age.” The CARDIA study showed signs of atherosclerosis in patients as young as in their twenties. This paradigm shift to early detection will now be possible thanks to technological advances like 3D vascular ultrasound.
Maron said he agrees with screening earlier in life. “The risk of having an event is related to the plaque burden and the number of years that a patient has been exposed to that burden. The earlier in life we can identify the burden to slow, arrest, or even reverse the plaque, the better.”
Maron points out that the study looked at an older population and did not include information on cause of death. While a study of younger people and data on cardiac causes of death would be useful, he says the study’s conclusions remain significant.
3D Vascular Ultrasound vs Coronary Artery Calcium
While both imaging methods in the study predicted death better than cardiovascular risk factors alone, each option has advantages.
For coronary artery calcium, “there’s a huge amount of literature demonstrating the association with cardiovascular events, there’s a standardized scoring system, there are widespread facilities for computed tomography, and there is not a lot of variability in the measurement — it’s not dependent on the operator,” said Maron.
But there is one drawback. The scoring system –— the Agatston score — can paradoxically go up following aggressive lowering of low-density lipoprotein cholesterol. “Once coronary calcium is present, it is challenging to interpret a repeat scan because we don’t know if the increase in score is due to progression or increasing density of the calcium, which is a sign of healing,” said Maron.
Vascular ultrasound avoids this problem and can also identify early noncalcified plaques and monitor their progression before they would appear on CT. Furthermore, the imaging does not add to lifetime radiation dose, as CT does, Fuster said.
3D ultrasound technology will soon be available in an inexpensive, automated, and easy-to-use format, he explains. Fuster envisions a scenario in which a nurse in a low-income country, using a cell phone app, will be able to assess atherosclerosis in a patient’s femoral artery. “In less than 1 hour, we can predict disease much more rigorously than with risk factors alone,” he said. “I think this is very exciting.”
Progression Increases Risk
Finding any atherosclerosis means an increased risk for death, but a greater burden or amount of atherosclerosis increases that risk, said Fuster. Progression of atherosclerosis increases risk even further.
The study looked at changes in atherosclerosis burden on vascular ultrasound in a subset of 732 patients a median of 8.9 years after their first test. Those with progression had a higher risk for death than those with regression or no atherosclerosis. “Progression is much more significant in predicting mortality than atherosclerosis findings alone,” Fuster said.
Maron said this finding points to “two great values from noninvasive imaging of atherosclerosis.” Not only does imaging detect atherosclerosis, but it can also characterize the burden and any calcification. Further, it allows doctors to monitor the response to interventions such as lifestyle changes and medical therapy. “Serial imaging of plaque burden will really enhance the management of atherosclerosis,” said Maron. “If we discover that someone is progressing rapidly, we can intensify therapy.”
He says imaging results also provide needed motivation for both clinicians and patients to take action that would prevent the deaths that result from atherosclerosis.
A version of this article appeared on Medscape.com.
Subclinical disease detected on imaging predicts death, report investigators who show that plaque burden found on 3D vascular ultrasound and coronary artery calcium on CT were better predictors of death than traditional risk factors.
The work not only highlights the importance of early detection, but it also has clinical implications, said Valentin Fuster, MD, president of the Mount Sinai Fuster Heart Hospital in New York. “It’s going to change things,” he said. “What I believe is going to happen is that we will begin to evaluate people with risk factors at age 30 using imaging. Today, we evaluate people at age 50 using clinical practice guidelines.”
Fuster’s team developed 3D vascular ultrasound to assess plaque burden and applied it in a prospective cohort study known as BioImage. The researchers assessed 6102 patients in Chicago, Illinois, and Fort Lauderdale, Florida, using 3D vascular ultrasound of the carotid artery and another well-established modality — coronary artery calcium, determined by CT.
Participants had no cardiovascular symptoms, yet their plaque burden and calcium scores at the beginning of the study were significantly associated with death during the 15 years of follow-up, even after taking risk factors and medication into account. The results are published in the Journal of the American College of Cardiology.
“Now, there is no question that subclinical disease on imaging predicts mortality,” said Fuster.
David J. Maron, MD, a preventive cardiologist at the Stanford University School of Medicine in California, calls the finding “very important.”
“The presence of atherosclerosis is powerful knowledge to guide the intensity of therapy and to motivate patients and clinicians to treat it,” said Maron, who is the co-author of an accompanying editorial and was not involved in the study.
Predicting Risk Early
The research also showed that the risk for death increases if the burden of plaque in the carotid artery increases over time. Both plaque burden shown on 3D vascular ultrasound and coronary artery calcium on CT were better predictors of death than traditional risk factors.
Maron says recent studies of younger populations, such as Progression of Early Subclinical Atherosclerosis (PESA) and Coronary Artery Risk Development in Young Adults (CARDIA), show that “risk factors at a young age have much more impact on arterial disease than when we measure risk factors at older age.” The CARDIA study showed signs of atherosclerosis in patients as young as in their twenties. This paradigm shift to early detection will now be possible thanks to technological advances like 3D vascular ultrasound.
Maron said he agrees with screening earlier in life. “The risk of having an event is related to the plaque burden and the number of years that a patient has been exposed to that burden. The earlier in life we can identify the burden to slow, arrest, or even reverse the plaque, the better.”
Maron points out that the study looked at an older population and did not include information on cause of death. While a study of younger people and data on cardiac causes of death would be useful, he says the study’s conclusions remain significant.
3D Vascular Ultrasound vs Coronary Artery Calcium
While both imaging methods in the study predicted death better than cardiovascular risk factors alone, each option has advantages.
For coronary artery calcium, “there’s a huge amount of literature demonstrating the association with cardiovascular events, there’s a standardized scoring system, there are widespread facilities for computed tomography, and there is not a lot of variability in the measurement — it’s not dependent on the operator,” said Maron.
But there is one drawback. The scoring system –— the Agatston score — can paradoxically go up following aggressive lowering of low-density lipoprotein cholesterol. “Once coronary calcium is present, it is challenging to interpret a repeat scan because we don’t know if the increase in score is due to progression or increasing density of the calcium, which is a sign of healing,” said Maron.
Vascular ultrasound avoids this problem and can also identify early noncalcified plaques and monitor their progression before they would appear on CT. Furthermore, the imaging does not add to lifetime radiation dose, as CT does, Fuster said.
3D ultrasound technology will soon be available in an inexpensive, automated, and easy-to-use format, he explains. Fuster envisions a scenario in which a nurse in a low-income country, using a cell phone app, will be able to assess atherosclerosis in a patient’s femoral artery. “In less than 1 hour, we can predict disease much more rigorously than with risk factors alone,” he said. “I think this is very exciting.”
Progression Increases Risk
Finding any atherosclerosis means an increased risk for death, but a greater burden or amount of atherosclerosis increases that risk, said Fuster. Progression of atherosclerosis increases risk even further.
The study looked at changes in atherosclerosis burden on vascular ultrasound in a subset of 732 patients a median of 8.9 years after their first test. Those with progression had a higher risk for death than those with regression or no atherosclerosis. “Progression is much more significant in predicting mortality than atherosclerosis findings alone,” Fuster said.
Maron said this finding points to “two great values from noninvasive imaging of atherosclerosis.” Not only does imaging detect atherosclerosis, but it can also characterize the burden and any calcification. Further, it allows doctors to monitor the response to interventions such as lifestyle changes and medical therapy. “Serial imaging of plaque burden will really enhance the management of atherosclerosis,” said Maron. “If we discover that someone is progressing rapidly, we can intensify therapy.”
He says imaging results also provide needed motivation for both clinicians and patients to take action that would prevent the deaths that result from atherosclerosis.
A version of this article appeared on Medscape.com.
Trial of Impella Heart Pump Stopped
An international trial of the Impella heart pump in patients with ST elevation myocardial infarction (STEMI) and cardiogenic shock has been stopped by the sponsor, Abiomed Inc. The termination followed news that another international trial, DanGer Shock, found that the pump improved survival in these patients.
“I was convinced that the study could not continue,” one of the principal investigators William O’Neill, MD, an interventional cardiologist with the Henry Ford Health in Detroit, said in an interview. After 3.5 years of work and thousands of person-hours, he added, “It’s not a decision that people took lightly.”
The trial already had three sites in Europe and one in the United States up and running, with two more US sites slated to join the trial. It had started enrolling patients, although few to date.
DanGer Shock trial results were expected to have a serious effect on how RECOVER IV would unfold. It was previously uncertain whether the Impella heart pump would save lives vs existing approaches, said O’Neill and co-principal investigator Navin Kapur, MD, an interventional cardiologist at Tufts Medical Center in Boston. Once the DanGer Shock trial showed the benefits of using the heart pump, that equipoise vanished.
Loss of Clinical Equipoise
“The clinicians were challenged in getting consent from patients where they had to say, ‘If you are randomized to the control arm, we are not able to use an Impella,’ ” said Dr. Kapur. He pointed out that patients would be unlikely to agree to participate in a trial where they might not get the treatment already shown to improve survival.
Dr. Kapur and Dr. O’Neill said the clinicians participating in the trial expressed discomfort at continuing. The RECOVER IV trial was expected to take many years to enroll the targeted number of patients. To participate, hospitals had to have the equipment and expertise to use the Impella heart pump, as well as the control treatments — balloon-pump support and extracorporeal membrane oxygenation (ECMO), Dr. Kapur explained. He said most patients with STEMI and cardiogenic shock would present to their nearest community hospitals, many of which would not have these treatments and would be unable to participate in the study.
Patients with STEMI and cardiogenic shock are uncommon. About 80,000 patients in the United States each year present with cardiogenic shock, of whom about 40% are not experiencing a STEMI, said Dr. O’Neill.
But those who do fit into the population of both STEMI and cardiogenic shock are at very high risk, said Dr. Kapur. “One in three or one in two patients with STEMI and cardiogenic shock will die in hospital.”
Getting Hearts Pumping
The Impella heart pump was originally developed by Impella Cardiosystems in Aachen, Germany, which was acquired by Abiomed in 2005, according to the Abiomed website. And Abiomed was acquired by Johnson & Johnson MedTech in 2022. The company has developed a series of models over the years and said that Impella CP — the model used in DanGer Shock and RECOVER IV trials — is the world’s smallest heart pump.
“Impella is the only heart pump that can be introduced percutaneously through the leg,” said Dr. O’Neill, whereas other pumps available are used only in open-heart surgery. While Impella is the first pump to be used this way, he said it won’t be the last. Other, more powerful pumps are being developed.
DanGer Shock: A Leap Forward
Despite leading to the halt of another trial, the DanGer Shock results are a good news story, said the RECOVER IV investigators.
“The DanGer trial is a huge advance,” said Dr. O’Neill. “It’s the first study this century that shows something that improves survival in cardiogenic shock. You treat eight patients, and you save one life.” Dr. O’Neill said this is one of the best outcomes he has seen during his long career.
Dr. Kapur said the DanGer trial is also a leap forward in designing trials for cardiogenic shock. He said previous trials of mechanical support in cardiogenic shock had neutral results, probably due to broad inclusion criteria for patients.
“The DanGer trial was selective in its inclusion and exclusion criteria. That made it more difficult to enroll the population, so it took a lot longer. But it used the right device at the right time in the right patient, and it was successful,” he said.
“The DanGer investigators need to be applauded,” he added. “The lesson is, we have to design the right trials.”
New Cardiogenic Shock Trials
Dr. O’Neill and Dr. Kapur said the groundwork they laid for RECOVER IV can be used for new trials.
“We have 50 sites in the US, Germany, and Denmark. They’re interested, and they’re waiting,” said Dr. O’Neill. The researchers are poised to begin new trials once protocols are developed.
What will the next trials investigate?
DanGer Shock results showed higher rates of adverse events following Impella use than after standard care. “We need to come up with strategies to decrease bleeding problems and renal failure,” said Dr. O’Neill, and these could be tested in trials.
Other questions he would like to see investigated are using the Impella heart pump before or after angioplasty, and multi-vessel vs culprit-vessel percutaneous coronary intervention in cardiogenic shock with Impella support.
Dr. Kapur mentioned studying patients excluded from the DanGer Shock trial — such as those needing right ventricular support — because DanGer Shock covered only left ventricular support and those suffering cardiac arrest outside hospital. He said trials could compare differences between models of Impella and investigate the role of ECMO.
“I’m optimistic that we can design more randomized controlled trials with the right patient population and right treatment algorithm,” Dr. Kapur said. This is a critical step toward better outcomes for patients, he added. Another step is optimizing the design of heart pumps, which should decrease the rates of adverse events, he said. “I have a lot of optimism for the future of device design.”
A version of this article first appeared on Medscape.com.
An international trial of the Impella heart pump in patients with ST elevation myocardial infarction (STEMI) and cardiogenic shock has been stopped by the sponsor, Abiomed Inc. The termination followed news that another international trial, DanGer Shock, found that the pump improved survival in these patients.
“I was convinced that the study could not continue,” one of the principal investigators William O’Neill, MD, an interventional cardiologist with the Henry Ford Health in Detroit, said in an interview. After 3.5 years of work and thousands of person-hours, he added, “It’s not a decision that people took lightly.”
The trial already had three sites in Europe and one in the United States up and running, with two more US sites slated to join the trial. It had started enrolling patients, although few to date.
DanGer Shock trial results were expected to have a serious effect on how RECOVER IV would unfold. It was previously uncertain whether the Impella heart pump would save lives vs existing approaches, said O’Neill and co-principal investigator Navin Kapur, MD, an interventional cardiologist at Tufts Medical Center in Boston. Once the DanGer Shock trial showed the benefits of using the heart pump, that equipoise vanished.
Loss of Clinical Equipoise
“The clinicians were challenged in getting consent from patients where they had to say, ‘If you are randomized to the control arm, we are not able to use an Impella,’ ” said Dr. Kapur. He pointed out that patients would be unlikely to agree to participate in a trial where they might not get the treatment already shown to improve survival.
Dr. Kapur and Dr. O’Neill said the clinicians participating in the trial expressed discomfort at continuing. The RECOVER IV trial was expected to take many years to enroll the targeted number of patients. To participate, hospitals had to have the equipment and expertise to use the Impella heart pump, as well as the control treatments — balloon-pump support and extracorporeal membrane oxygenation (ECMO), Dr. Kapur explained. He said most patients with STEMI and cardiogenic shock would present to their nearest community hospitals, many of which would not have these treatments and would be unable to participate in the study.
Patients with STEMI and cardiogenic shock are uncommon. About 80,000 patients in the United States each year present with cardiogenic shock, of whom about 40% are not experiencing a STEMI, said Dr. O’Neill.
But those who do fit into the population of both STEMI and cardiogenic shock are at very high risk, said Dr. Kapur. “One in three or one in two patients with STEMI and cardiogenic shock will die in hospital.”
Getting Hearts Pumping
The Impella heart pump was originally developed by Impella Cardiosystems in Aachen, Germany, which was acquired by Abiomed in 2005, according to the Abiomed website. And Abiomed was acquired by Johnson & Johnson MedTech in 2022. The company has developed a series of models over the years and said that Impella CP — the model used in DanGer Shock and RECOVER IV trials — is the world’s smallest heart pump.
“Impella is the only heart pump that can be introduced percutaneously through the leg,” said Dr. O’Neill, whereas other pumps available are used only in open-heart surgery. While Impella is the first pump to be used this way, he said it won’t be the last. Other, more powerful pumps are being developed.
DanGer Shock: A Leap Forward
Despite leading to the halt of another trial, the DanGer Shock results are a good news story, said the RECOVER IV investigators.
“The DanGer trial is a huge advance,” said Dr. O’Neill. “It’s the first study this century that shows something that improves survival in cardiogenic shock. You treat eight patients, and you save one life.” Dr. O’Neill said this is one of the best outcomes he has seen during his long career.
Dr. Kapur said the DanGer trial is also a leap forward in designing trials for cardiogenic shock. He said previous trials of mechanical support in cardiogenic shock had neutral results, probably due to broad inclusion criteria for patients.
“The DanGer trial was selective in its inclusion and exclusion criteria. That made it more difficult to enroll the population, so it took a lot longer. But it used the right device at the right time in the right patient, and it was successful,” he said.
“The DanGer investigators need to be applauded,” he added. “The lesson is, we have to design the right trials.”
New Cardiogenic Shock Trials
Dr. O’Neill and Dr. Kapur said the groundwork they laid for RECOVER IV can be used for new trials.
“We have 50 sites in the US, Germany, and Denmark. They’re interested, and they’re waiting,” said Dr. O’Neill. The researchers are poised to begin new trials once protocols are developed.
What will the next trials investigate?
DanGer Shock results showed higher rates of adverse events following Impella use than after standard care. “We need to come up with strategies to decrease bleeding problems and renal failure,” said Dr. O’Neill, and these could be tested in trials.
Other questions he would like to see investigated are using the Impella heart pump before or after angioplasty, and multi-vessel vs culprit-vessel percutaneous coronary intervention in cardiogenic shock with Impella support.
Dr. Kapur mentioned studying patients excluded from the DanGer Shock trial — such as those needing right ventricular support — because DanGer Shock covered only left ventricular support and those suffering cardiac arrest outside hospital. He said trials could compare differences between models of Impella and investigate the role of ECMO.
“I’m optimistic that we can design more randomized controlled trials with the right patient population and right treatment algorithm,” Dr. Kapur said. This is a critical step toward better outcomes for patients, he added. Another step is optimizing the design of heart pumps, which should decrease the rates of adverse events, he said. “I have a lot of optimism for the future of device design.”
A version of this article first appeared on Medscape.com.
An international trial of the Impella heart pump in patients with ST elevation myocardial infarction (STEMI) and cardiogenic shock has been stopped by the sponsor, Abiomed Inc. The termination followed news that another international trial, DanGer Shock, found that the pump improved survival in these patients.
“I was convinced that the study could not continue,” one of the principal investigators William O’Neill, MD, an interventional cardiologist with the Henry Ford Health in Detroit, said in an interview. After 3.5 years of work and thousands of person-hours, he added, “It’s not a decision that people took lightly.”
The trial already had three sites in Europe and one in the United States up and running, with two more US sites slated to join the trial. It had started enrolling patients, although few to date.
DanGer Shock trial results were expected to have a serious effect on how RECOVER IV would unfold. It was previously uncertain whether the Impella heart pump would save lives vs existing approaches, said O’Neill and co-principal investigator Navin Kapur, MD, an interventional cardiologist at Tufts Medical Center in Boston. Once the DanGer Shock trial showed the benefits of using the heart pump, that equipoise vanished.
Loss of Clinical Equipoise
“The clinicians were challenged in getting consent from patients where they had to say, ‘If you are randomized to the control arm, we are not able to use an Impella,’ ” said Dr. Kapur. He pointed out that patients would be unlikely to agree to participate in a trial where they might not get the treatment already shown to improve survival.
Dr. Kapur and Dr. O’Neill said the clinicians participating in the trial expressed discomfort at continuing. The RECOVER IV trial was expected to take many years to enroll the targeted number of patients. To participate, hospitals had to have the equipment and expertise to use the Impella heart pump, as well as the control treatments — balloon-pump support and extracorporeal membrane oxygenation (ECMO), Dr. Kapur explained. He said most patients with STEMI and cardiogenic shock would present to their nearest community hospitals, many of which would not have these treatments and would be unable to participate in the study.
Patients with STEMI and cardiogenic shock are uncommon. About 80,000 patients in the United States each year present with cardiogenic shock, of whom about 40% are not experiencing a STEMI, said Dr. O’Neill.
But those who do fit into the population of both STEMI and cardiogenic shock are at very high risk, said Dr. Kapur. “One in three or one in two patients with STEMI and cardiogenic shock will die in hospital.”
Getting Hearts Pumping
The Impella heart pump was originally developed by Impella Cardiosystems in Aachen, Germany, which was acquired by Abiomed in 2005, according to the Abiomed website. And Abiomed was acquired by Johnson & Johnson MedTech in 2022. The company has developed a series of models over the years and said that Impella CP — the model used in DanGer Shock and RECOVER IV trials — is the world’s smallest heart pump.
“Impella is the only heart pump that can be introduced percutaneously through the leg,” said Dr. O’Neill, whereas other pumps available are used only in open-heart surgery. While Impella is the first pump to be used this way, he said it won’t be the last. Other, more powerful pumps are being developed.
DanGer Shock: A Leap Forward
Despite leading to the halt of another trial, the DanGer Shock results are a good news story, said the RECOVER IV investigators.
“The DanGer trial is a huge advance,” said Dr. O’Neill. “It’s the first study this century that shows something that improves survival in cardiogenic shock. You treat eight patients, and you save one life.” Dr. O’Neill said this is one of the best outcomes he has seen during his long career.
Dr. Kapur said the DanGer trial is also a leap forward in designing trials for cardiogenic shock. He said previous trials of mechanical support in cardiogenic shock had neutral results, probably due to broad inclusion criteria for patients.
“The DanGer trial was selective in its inclusion and exclusion criteria. That made it more difficult to enroll the population, so it took a lot longer. But it used the right device at the right time in the right patient, and it was successful,” he said.
“The DanGer investigators need to be applauded,” he added. “The lesson is, we have to design the right trials.”
New Cardiogenic Shock Trials
Dr. O’Neill and Dr. Kapur said the groundwork they laid for RECOVER IV can be used for new trials.
“We have 50 sites in the US, Germany, and Denmark. They’re interested, and they’re waiting,” said Dr. O’Neill. The researchers are poised to begin new trials once protocols are developed.
What will the next trials investigate?
DanGer Shock results showed higher rates of adverse events following Impella use than after standard care. “We need to come up with strategies to decrease bleeding problems and renal failure,” said Dr. O’Neill, and these could be tested in trials.
Other questions he would like to see investigated are using the Impella heart pump before or after angioplasty, and multi-vessel vs culprit-vessel percutaneous coronary intervention in cardiogenic shock with Impella support.
Dr. Kapur mentioned studying patients excluded from the DanGer Shock trial — such as those needing right ventricular support — because DanGer Shock covered only left ventricular support and those suffering cardiac arrest outside hospital. He said trials could compare differences between models of Impella and investigate the role of ECMO.
“I’m optimistic that we can design more randomized controlled trials with the right patient population and right treatment algorithm,” Dr. Kapur said. This is a critical step toward better outcomes for patients, he added. Another step is optimizing the design of heart pumps, which should decrease the rates of adverse events, he said. “I have a lot of optimism for the future of device design.”
A version of this article first appeared on Medscape.com.