Interventional Cardiology & Surgery

A new study offers early validation of the recently released Valve Academic Research Consortium 3 (VARC-3) definition of technical success after transcatheter aortic valve replacement (TAVR) and highlights its role in patient prognosis.

Results show that one in 10 patients (11.6%) undergoing TAVR with contemporary devices and techniques experiences technical failure, according to VARC-3.

At 30 days, patients with technical failure had significantly higher rates of the composite of cardiovascular (CV) death or stroke (11.5% vs. 3.5%), CV death (6.0% vs. 1.0%), and stroke (7.2% vs. 2.9%), compared with those with technical success.

Technical failure after TAVR was also independently associated with a twofold higher risk for CV death or stroke at 1 year (20.0% vs. 10.3%; hazard ratio, 2.01; 95% CI, 1.37-2.95).

Other independent predictors were history of peripheral artery disease (HR, 1.97), New York Heart Association III or IV disease (HR, 1.86), baseline moderate or greater mitral regurgitation (HR, 1.48), atrial fibrillation (HR, 1.40), and Society of Thoracic Surgeons predicted mortality risk (HR, 1.04).

“We were expecting that we were getting better over time with device iterations, with more experience, so we weren’t surprised by the result. But I think what is somewhat surprising is how much of an impact it has on the outcome,” senior study author Thomas Pilgrim, MD, Inselspital, University of Bern, Switzerland, told this news organization.

The VARC-3 document, introduced last year to some controversy, features a heavier focus on patient outcomes, as well as composite safety and efficacy endpoints. The definition of technical success after TAVR includes freedom from death; successful access, delivery of the device, and retrieval of the delivery system; correct positioning of a prosthetic heart valve into the proper anatomical location; and freedom from surgery or intervention related to the device or to an access-related or cardiac structural complication.

The composite endpoint is meant to replace the VARC-2 definition of “device success,” which also included freedom from death and correct valve positioning but required echocardiographic evaluation. With VARC-3, there is an “immediate measure” of success without having to wait for echocardiography, observed Dr. Pilgrim.

As reported in the Journal of the American College of Cardiology Cardiovascular Interventions, TAVR was a technical success in 1,435 of 1,624 (88.4%) patients. Technical failure occurred in 189 patients related to either vascular complications (8.6%) or procedural death or cardiac complications (3.0%).

The VARC-2 endpoint of device success was observed in 66.1% of patients. The high rate of device failure was largely attributed to a 28% incidence of prosthesis-patient mismatch.

“If you use the VARC-2 device success [definition], you include this patient–prosthesis mismatch, the [valve] gradients, [and] regurgitation and then device success is always lower,” Dr. Pilgrim said.

Asked whether the VARC-3 definition may be missing case failures, he replied: “At this stage, we don’t know how important these echocardiographic parameters are for hard clinical endpoints. Maybe the VARC-2 endpoint was too sensitive or the VARC-3 endpoint is not sensitive enough. This is something we just don’t know at this stage.”

Marco Barbanti, MD, an interventional cardiologist at Rodolico Polyclinic University Hospital-San Marco, Catania, Italy, and author of an accompanying editorial, said VARC-3 represents a more accurate indicator of immediate success of the procedure.

“It’s a more pertinent definition according to what really has an impact on prognosis, and, according to the results of this paper, actually, the calibration of this new definition is quite good,” Dr. Barbanti said in an interview.

Patients with VARC-3 technical failure were older, had a higher body mass index, and had more advanced heart failure symptoms than those with technical success. There were no significant differences between the two groups in echocardiographic or CT data, anesthetic strategy, valve type or size, or use of pre- or post-dilation.

All patients underwent TAVR with current balloon-expandable (Sapien 3/Sapien Ultra, Edwards Lifesciences) or self-expanding (Evolut R/PRO [Medtronic], Portico [Abbott], Symetis ACURATE/ACURATE neo [Boston Scientific]) devices between March 2012 and December 2019. A transfemoral approach was used in 92.5% of patients.

In a landmark analysis with the landmark set at 30 days, the effect of technical failure on adverse outcome was limited to the first 30 days (composite endpoint 0-30 days: HR, 3.42; P < .001; 30-360 days: HR, 1.36; P = .266; P for interaction = .002).

At 1 year, the composite of CV death and stroke endpoint occurred in 24.1% of patients with cardiac technical failure, in 18.8% of patients with vascular technical failure, and in 10.3% of patients with technical success.

In multivariate analyses, cardiac and vascular technical failures were independently associated with a 2.6-fold and 1.9-fold increased risk, respectively, for the composite of cardiovascular death and stroke at 1 year.

Female sex, larger device landing zone calcium volume, and earlier procedures (March 2012 to July 2016) were associated with a higher risk for cardiac technical failure, whereas, consistent with previous studies, higher body mass index and use of the Prostar/Manta versus the ProGlide closure device predicted vascular technical failure.

The findings “underscore that technical success is highly clinically relevant and may serve as one of the pivotal endpoints to evaluate the improvement of TAVR or for head-to-head comparisons of new devices in future clinical trials,” the authors conclude.

The findings reflect the experience of a single high-volume center with highly experienced operators in the prospective BERN TAVR registry, however, and may not be generalizable to other heart centers, they note. Although the registry has standardized follow-up, independent analysis of echocardiographic and CT, and independent event adjudication, vascular anatomy was not systematically assessed, and the potential exists for confounding from unmeasured variables.

Dr. Pilgrim reports research grants to the institution from Edwards Lifesciences, Boston Scientific, and Biotronik, personal fees from Biotronik and Boston Scientific, and other from HighLife SAS. Dr. Barbanti is a consultant for Edwards Lifesciences and Boston Scientific.

A version of this article first appeared on Medscape.com.

A new study offers early validation of the recently released Valve Academic Research Consortium 3 (VARC-3) definition of technical success after transcatheter aortic valve replacement (TAVR) and highlights its role in patient prognosis.

Results show that one in 10 patients (11.6%) undergoing TAVR with contemporary devices and techniques experiences technical failure, according to VARC-3.

At 30 days, patients with technical failure had significantly higher rates of the composite of cardiovascular (CV) death or stroke (11.5% vs. 3.5%), CV death (6.0% vs. 1.0%), and stroke (7.2% vs. 2.9%), compared with those with technical success.

Technical failure after TAVR was also independently associated with a twofold higher risk for CV death or stroke at 1 year (20.0% vs. 10.3%; hazard ratio, 2.01; 95% CI, 1.37-2.95).

Other independent predictors were history of peripheral artery disease (HR, 1.97), New York Heart Association III or IV disease (HR, 1.86), baseline moderate or greater mitral regurgitation (HR, 1.48), atrial fibrillation (HR, 1.40), and Society of Thoracic Surgeons predicted mortality risk (HR, 1.04).

“We were expecting that we were getting better over time with device iterations, with more experience, so we weren’t surprised by the result. But I think what is somewhat surprising is how much of an impact it has on the outcome,” senior study author Thomas Pilgrim, MD, Inselspital, University of Bern, Switzerland, told this news organization.

The VARC-3 document, introduced last year to some controversy, features a heavier focus on patient outcomes, as well as composite safety and efficacy endpoints. The definition of technical success after TAVR includes freedom from death; successful access, delivery of the device, and retrieval of the delivery system; correct positioning of a prosthetic heart valve into the proper anatomical location; and freedom from surgery or intervention related to the device or to an access-related or cardiac structural complication.

The composite endpoint is meant to replace the VARC-2 definition of “device success,” which also included freedom from death and correct valve positioning but required echocardiographic evaluation. With VARC-3, there is an “immediate measure” of success without having to wait for echocardiography, observed Dr. Pilgrim.

As reported in the Journal of the American College of Cardiology Cardiovascular Interventions, TAVR was a technical success in 1,435 of 1,624 (88.4%) patients. Technical failure occurred in 189 patients related to either vascular complications (8.6%) or procedural death or cardiac complications (3.0%).

The VARC-2 endpoint of device success was observed in 66.1% of patients. The high rate of device failure was largely attributed to a 28% incidence of prosthesis-patient mismatch.

“If you use the VARC-2 device success [definition], you include this patient–prosthesis mismatch, the [valve] gradients, [and] regurgitation and then device success is always lower,” Dr. Pilgrim said.

Asked whether the VARC-3 definition may be missing case failures, he replied: “At this stage, we don’t know how important these echocardiographic parameters are for hard clinical endpoints. Maybe the VARC-2 endpoint was too sensitive or the VARC-3 endpoint is not sensitive enough. This is something we just don’t know at this stage.”

Marco Barbanti, MD, an interventional cardiologist at Rodolico Polyclinic University Hospital-San Marco, Catania, Italy, and author of an accompanying editorial, said VARC-3 represents a more accurate indicator of immediate success of the procedure.

“It’s a more pertinent definition according to what really has an impact on prognosis, and, according to the results of this paper, actually, the calibration of this new definition is quite good,” Dr. Barbanti said in an interview.

Patients with VARC-3 technical failure were older, had a higher body mass index, and had more advanced heart failure symptoms than those with technical success. There were no significant differences between the two groups in echocardiographic or CT data, anesthetic strategy, valve type or size, or use of pre- or post-dilation.

All patients underwent TAVR with current balloon-expandable (Sapien 3/Sapien Ultra, Edwards Lifesciences) or self-expanding (Evolut R/PRO [Medtronic], Portico [Abbott], Symetis ACURATE/ACURATE neo [Boston Scientific]) devices between March 2012 and December 2019. A transfemoral approach was used in 92.5% of patients.

In a landmark analysis with the landmark set at 30 days, the effect of technical failure on adverse outcome was limited to the first 30 days (composite endpoint 0-30 days: HR, 3.42; P < .001; 30-360 days: HR, 1.36; P = .266; P for interaction = .002).

At 1 year, the composite of CV death and stroke endpoint occurred in 24.1% of patients with cardiac technical failure, in 18.8% of patients with vascular technical failure, and in 10.3% of patients with technical success.

In multivariate analyses, cardiac and vascular technical failures were independently associated with a 2.6-fold and 1.9-fold increased risk, respectively, for the composite of cardiovascular death and stroke at 1 year.

Female sex, larger device landing zone calcium volume, and earlier procedures (March 2012 to July 2016) were associated with a higher risk for cardiac technical failure, whereas, consistent with previous studies, higher body mass index and use of the Prostar/Manta versus the ProGlide closure device predicted vascular technical failure.

The findings “underscore that technical success is highly clinically relevant and may serve as one of the pivotal endpoints to evaluate the improvement of TAVR or for head-to-head comparisons of new devices in future clinical trials,” the authors conclude.

The findings reflect the experience of a single high-volume center with highly experienced operators in the prospective BERN TAVR registry, however, and may not be generalizable to other heart centers, they note. Although the registry has standardized follow-up, independent analysis of echocardiographic and CT, and independent event adjudication, vascular anatomy was not systematically assessed, and the potential exists for confounding from unmeasured variables.

Dr. Pilgrim reports research grants to the institution from Edwards Lifesciences, Boston Scientific, and Biotronik, personal fees from Biotronik and Boston Scientific, and other from HighLife SAS. Dr. Barbanti is a consultant for Edwards Lifesciences and Boston Scientific.

A version of this article first appeared on Medscape.com.

A new study offers early validation of the recently released Valve Academic Research Consortium 3 (VARC-3) definition of technical success after transcatheter aortic valve replacement (TAVR) and highlights its role in patient prognosis.

Results show that one in 10 patients (11.6%) undergoing TAVR with contemporary devices and techniques experiences technical failure, according to VARC-3.

At 30 days, patients with technical failure had significantly higher rates of the composite of cardiovascular (CV) death or stroke (11.5% vs. 3.5%), CV death (6.0% vs. 1.0%), and stroke (7.2% vs. 2.9%), compared with those with technical success.

Technical failure after TAVR was also independently associated with a twofold higher risk for CV death or stroke at 1 year (20.0% vs. 10.3%; hazard ratio, 2.01; 95% CI, 1.37-2.95).

Other independent predictors were history of peripheral artery disease (HR, 1.97), New York Heart Association III or IV disease (HR, 1.86), baseline moderate or greater mitral regurgitation (HR, 1.48), atrial fibrillation (HR, 1.40), and Society of Thoracic Surgeons predicted mortality risk (HR, 1.04).

“We were expecting that we were getting better over time with device iterations, with more experience, so we weren’t surprised by the result. But I think what is somewhat surprising is how much of an impact it has on the outcome,” senior study author Thomas Pilgrim, MD, Inselspital, University of Bern, Switzerland, told this news organization.

The VARC-3 document, introduced last year to some controversy, features a heavier focus on patient outcomes, as well as composite safety and efficacy endpoints. The definition of technical success after TAVR includes freedom from death; successful access, delivery of the device, and retrieval of the delivery system; correct positioning of a prosthetic heart valve into the proper anatomical location; and freedom from surgery or intervention related to the device or to an access-related or cardiac structural complication.

The composite endpoint is meant to replace the VARC-2 definition of “device success,” which also included freedom from death and correct valve positioning but required echocardiographic evaluation. With VARC-3, there is an “immediate measure” of success without having to wait for echocardiography, observed Dr. Pilgrim.

As reported in the Journal of the American College of Cardiology Cardiovascular Interventions, TAVR was a technical success in 1,435 of 1,624 (88.4%) patients. Technical failure occurred in 189 patients related to either vascular complications (8.6%) or procedural death or cardiac complications (3.0%).

The VARC-2 endpoint of device success was observed in 66.1% of patients. The high rate of device failure was largely attributed to a 28% incidence of prosthesis-patient mismatch.

“If you use the VARC-2 device success [definition], you include this patient–prosthesis mismatch, the [valve] gradients, [and] regurgitation and then device success is always lower,” Dr. Pilgrim said.

Asked whether the VARC-3 definition may be missing case failures, he replied: “At this stage, we don’t know how important these echocardiographic parameters are for hard clinical endpoints. Maybe the VARC-2 endpoint was too sensitive or the VARC-3 endpoint is not sensitive enough. This is something we just don’t know at this stage.”

Marco Barbanti, MD, an interventional cardiologist at Rodolico Polyclinic University Hospital-San Marco, Catania, Italy, and author of an accompanying editorial, said VARC-3 represents a more accurate indicator of immediate success of the procedure.

“It’s a more pertinent definition according to what really has an impact on prognosis, and, according to the results of this paper, actually, the calibration of this new definition is quite good,” Dr. Barbanti said in an interview.

Patients with VARC-3 technical failure were older, had a higher body mass index, and had more advanced heart failure symptoms than those with technical success. There were no significant differences between the two groups in echocardiographic or CT data, anesthetic strategy, valve type or size, or use of pre- or post-dilation.

All patients underwent TAVR with current balloon-expandable (Sapien 3/Sapien Ultra, Edwards Lifesciences) or self-expanding (Evolut R/PRO [Medtronic], Portico [Abbott], Symetis ACURATE/ACURATE neo [Boston Scientific]) devices between March 2012 and December 2019. A transfemoral approach was used in 92.5% of patients.

In a landmark analysis with the landmark set at 30 days, the effect of technical failure on adverse outcome was limited to the first 30 days (composite endpoint 0-30 days: HR, 3.42; P < .001; 30-360 days: HR, 1.36; P = .266; P for interaction = .002).

At 1 year, the composite of CV death and stroke endpoint occurred in 24.1% of patients with cardiac technical failure, in 18.8% of patients with vascular technical failure, and in 10.3% of patients with technical success.

In multivariate analyses, cardiac and vascular technical failures were independently associated with a 2.6-fold and 1.9-fold increased risk, respectively, for the composite of cardiovascular death and stroke at 1 year.

Female sex, larger device landing zone calcium volume, and earlier procedures (March 2012 to July 2016) were associated with a higher risk for cardiac technical failure, whereas, consistent with previous studies, higher body mass index and use of the Prostar/Manta versus the ProGlide closure device predicted vascular technical failure.

The findings “underscore that technical success is highly clinically relevant and may serve as one of the pivotal endpoints to evaluate the improvement of TAVR or for head-to-head comparisons of new devices in future clinical trials,” the authors conclude.

The findings reflect the experience of a single high-volume center with highly experienced operators in the prospective BERN TAVR registry, however, and may not be generalizable to other heart centers, they note. Although the registry has standardized follow-up, independent analysis of echocardiographic and CT, and independent event adjudication, vascular anatomy was not systematically assessed, and the potential exists for confounding from unmeasured variables.

Dr. Pilgrim reports research grants to the institution from Edwards Lifesciences, Boston Scientific, and Biotronik, personal fees from Biotronik and Boston Scientific, and other from HighLife SAS. Dr. Barbanti is a consultant for Edwards Lifesciences and Boston Scientific.

A version of this article first appeared on Medscape.com.

The widely held notion that consuming small to moderate amounts of alcohol is good for cardiovascular health is not supported by the data, the World Heart Federation says in a new policy brief.

In fact, the evidence is clear that any level of drinking can contribute to loss of a healthy life, the organization says.

“Over the past several decades, the prevalence of cardiovascular disease has nearly doubled, and alcohol has played a major role in the incidence of much of it,” the WHF said in the brief.

“The portrayal of alcohol as necessary for a vibrant social life has diverted attention from the harms of alcohol use, as have the frequent and widely publicized claims that moderate drinking, such as a glass of red wine a day, can offer protection against cardiovascular disease,” Monika Arora, PhD, member of the WHF advocacy committee and coauthor of the brief, said in a news release.

“These claims are at best misinformed and at worst an attempt by the alcohol industry to mislead the public about the danger of their product,” Dr. Arora added.

The WHF conclusions follow a report in the Lancet based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), which found that there is no safe level of alcohol consumption.

In 2019, nearly 2.4 million deaths were attributed to alcohol, accounting for 4.3% of all deaths globally and 12.6% of deaths in men 15 to 49 years of age.

Even small amounts of alcohol have been shown to raise the risk for cardiovascular disease, including coronary disease, stroke, heart failure, hypertensive heart disease, cardiomyopathy, atrial fibrillation, and aneurysm, the WHF notes.

Studies that claim otherwise are largely based on purely observational research, which fails to account for relevant cofactors, the organization writes.

Based on their summary of the evidence to date, there is no reliable correlation between moderate alcohol consumption and a lower risk for cardiovascular disease.

Alcohol use is also a “major avoidable risk factor” for cancer, digestive diseases, intentional and unintentional injuries, and several infectious diseases, the WHF says.

Alcohol use also has significant economic and social costs, which include costs to individuals and health systems, productivity losses, as well as the increased risk for violence, homelessness, and criminal activity.

The WHF policy brief calls for “urgent and decisive action” to tackle the unprecedented rise in alcohol-related death and disability worldwide.

Recommended actions include boosting restrictions on alcohol availability; advancing and enforcing drinking and driving countermeasures; increasing access to screening, brief interventions, and treatment for alcohol use disorder; enforcing bans on alcohol advertising; establishing a uniform minimum legal drinking age; and mandating health warnings on alcohol products.

A version of this article first appeared on Medscape.com.

The widely held notion that consuming small to moderate amounts of alcohol is good for cardiovascular health is not supported by the data, the World Heart Federation says in a new policy brief.

In fact, the evidence is clear that any level of drinking can contribute to loss of a healthy life, the organization says.

“Over the past several decades, the prevalence of cardiovascular disease has nearly doubled, and alcohol has played a major role in the incidence of much of it,” the WHF said in the brief.

“The portrayal of alcohol as necessary for a vibrant social life has diverted attention from the harms of alcohol use, as have the frequent and widely publicized claims that moderate drinking, such as a glass of red wine a day, can offer protection against cardiovascular disease,” Monika Arora, PhD, member of the WHF advocacy committee and coauthor of the brief, said in a news release.

“These claims are at best misinformed and at worst an attempt by the alcohol industry to mislead the public about the danger of their product,” Dr. Arora added.

The WHF conclusions follow a report in the Lancet based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), which found that there is no safe level of alcohol consumption.

In 2019, nearly 2.4 million deaths were attributed to alcohol, accounting for 4.3% of all deaths globally and 12.6% of deaths in men 15 to 49 years of age.

Even small amounts of alcohol have been shown to raise the risk for cardiovascular disease, including coronary disease, stroke, heart failure, hypertensive heart disease, cardiomyopathy, atrial fibrillation, and aneurysm, the WHF notes.

Studies that claim otherwise are largely based on purely observational research, which fails to account for relevant cofactors, the organization writes.

Based on their summary of the evidence to date, there is no reliable correlation between moderate alcohol consumption and a lower risk for cardiovascular disease.

Alcohol use is also a “major avoidable risk factor” for cancer, digestive diseases, intentional and unintentional injuries, and several infectious diseases, the WHF says.

Alcohol use also has significant economic and social costs, which include costs to individuals and health systems, productivity losses, as well as the increased risk for violence, homelessness, and criminal activity.

The WHF policy brief calls for “urgent and decisive action” to tackle the unprecedented rise in alcohol-related death and disability worldwide.

Recommended actions include boosting restrictions on alcohol availability; advancing and enforcing drinking and driving countermeasures; increasing access to screening, brief interventions, and treatment for alcohol use disorder; enforcing bans on alcohol advertising; establishing a uniform minimum legal drinking age; and mandating health warnings on alcohol products.

A version of this article first appeared on Medscape.com.

The widely held notion that consuming small to moderate amounts of alcohol is good for cardiovascular health is not supported by the data, the World Heart Federation says in a new policy brief.

In fact, the evidence is clear that any level of drinking can contribute to loss of a healthy life, the organization says.

“Over the past several decades, the prevalence of cardiovascular disease has nearly doubled, and alcohol has played a major role in the incidence of much of it,” the WHF said in the brief.

“The portrayal of alcohol as necessary for a vibrant social life has diverted attention from the harms of alcohol use, as have the frequent and widely publicized claims that moderate drinking, such as a glass of red wine a day, can offer protection against cardiovascular disease,” Monika Arora, PhD, member of the WHF advocacy committee and coauthor of the brief, said in a news release.

“These claims are at best misinformed and at worst an attempt by the alcohol industry to mislead the public about the danger of their product,” Dr. Arora added.

The WHF conclusions follow a report in the Lancet based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), which found that there is no safe level of alcohol consumption.

In 2019, nearly 2.4 million deaths were attributed to alcohol, accounting for 4.3% of all deaths globally and 12.6% of deaths in men 15 to 49 years of age.

Even small amounts of alcohol have been shown to raise the risk for cardiovascular disease, including coronary disease, stroke, heart failure, hypertensive heart disease, cardiomyopathy, atrial fibrillation, and aneurysm, the WHF notes.

Studies that claim otherwise are largely based on purely observational research, which fails to account for relevant cofactors, the organization writes.

Based on their summary of the evidence to date, there is no reliable correlation between moderate alcohol consumption and a lower risk for cardiovascular disease.

Alcohol use is also a “major avoidable risk factor” for cancer, digestive diseases, intentional and unintentional injuries, and several infectious diseases, the WHF says.

Alcohol use also has significant economic and social costs, which include costs to individuals and health systems, productivity losses, as well as the increased risk for violence, homelessness, and criminal activity.

The WHF policy brief calls for “urgent and decisive action” to tackle the unprecedented rise in alcohol-related death and disability worldwide.

Recommended actions include boosting restrictions on alcohol availability; advancing and enforcing drinking and driving countermeasures; increasing access to screening, brief interventions, and treatment for alcohol use disorder; enforcing bans on alcohol advertising; establishing a uniform minimum legal drinking age; and mandating health warnings on alcohol products.

A version of this article first appeared on Medscape.com.

Medtronic has recalled 95,110 HawkOne Directional Atherectomy Systems because of the risk of the guidewire within the catheter moving downward or prolapsing during use, which may damage the tip of the catheter.

The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.

The HawkOne Directional Atherectomy system is used during procedures intended to remove blockage from peripheral arteries and improve blood flow.

If the guideline moves downward or prolapses during use, the “catheter tip may break off or separate, and this could lead to serious adverse events, including a tear along the inside wall of an artery (arterial dissection), a rupture or breakage of an artery (arterial rupture), decrease in blood flow to a part of the body because of a blocked artery (ischemia), and/or blood vessel complications that could require surgical repair and additional procedures to capture and remove the detached and/or migrated (embolized) tip,” the FDA says in a recall notice posted today on its website.

To date, there have been 55 injuries, no deaths, and 163 complaints reported for this device.

The recalled devices were distributed in the United States between Jan. 22, 2018 and Oct. 4, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website.

Medtronic sent an urgent field safety notice to customers Dec. 6, 2021, requesting that they alert parties of the defect, review the instructions for use before using the device, and note the warnings and precautions listed in the letter.

Customers were also asked to complete the enclosed confirmation form and email to rs.cfqfca@medtronic.com.

Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

A version of this article first appeared on Medscape.com.

Medtronic has recalled 95,110 HawkOne Directional Atherectomy Systems because of the risk of the guidewire within the catheter moving downward or prolapsing during use, which may damage the tip of the catheter.

The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.

The HawkOne Directional Atherectomy system is used during procedures intended to remove blockage from peripheral arteries and improve blood flow.

If the guideline moves downward or prolapses during use, the “catheter tip may break off or separate, and this could lead to serious adverse events, including a tear along the inside wall of an artery (arterial dissection), a rupture or breakage of an artery (arterial rupture), decrease in blood flow to a part of the body because of a blocked artery (ischemia), and/or blood vessel complications that could require surgical repair and additional procedures to capture and remove the detached and/or migrated (embolized) tip,” the FDA says in a recall notice posted today on its website.

To date, there have been 55 injuries, no deaths, and 163 complaints reported for this device.

The recalled devices were distributed in the United States between Jan. 22, 2018 and Oct. 4, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website.

Medtronic sent an urgent field safety notice to customers Dec. 6, 2021, requesting that they alert parties of the defect, review the instructions for use before using the device, and note the warnings and precautions listed in the letter.

Customers were also asked to complete the enclosed confirmation form and email to rs.cfqfca@medtronic.com.

Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

A version of this article first appeared on Medscape.com.

Medtronic has recalled 95,110 HawkOne Directional Atherectomy Systems because of the risk of the guidewire within the catheter moving downward or prolapsing during use, which may damage the tip of the catheter.

The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.

The HawkOne Directional Atherectomy system is used during procedures intended to remove blockage from peripheral arteries and improve blood flow.

If the guideline moves downward or prolapses during use, the “catheter tip may break off or separate, and this could lead to serious adverse events, including a tear along the inside wall of an artery (arterial dissection), a rupture or breakage of an artery (arterial rupture), decrease in blood flow to a part of the body because of a blocked artery (ischemia), and/or blood vessel complications that could require surgical repair and additional procedures to capture and remove the detached and/or migrated (embolized) tip,” the FDA says in a recall notice posted today on its website.

To date, there have been 55 injuries, no deaths, and 163 complaints reported for this device.

The recalled devices were distributed in the United States between Jan. 22, 2018 and Oct. 4, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website.

Medtronic sent an urgent field safety notice to customers Dec. 6, 2021, requesting that they alert parties of the defect, review the instructions for use before using the device, and note the warnings and precautions listed in the letter.

Customers were also asked to complete the enclosed confirmation form and email to rs.cfqfca@medtronic.com.

Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

A version of this article first appeared on Medscape.com.

Patients who do not receive care for non–ST-segment elevation myocardial infarction (NSTEMI) within 24 hours have a substantially increased risk of mortality 3 years later when compared with those receiving earlier intervention, according to a population-based study evaluating more than 6,000 patients.

The characteristics of patients receiving NSTEMI care more than 24 hours after symptom onset were different from those treated earlier, but understanding these differences might provide clues for improved pathways to care, according to the investigators of this study, published in the Journal of the American College of Cardiology.

In a study of 6,544 NSTEMI patients in the Korea Acute Myocardial Infarction Registry, 1,827 (27%) were evaluated and treated 24 hours or more after symptom onset. When compared with the group with a shorter symptom-to-door time, outcomes at a median follow-up of 1,098 days were substantially worse.

Most importantly, this included a more than 50% absolute unadjusted increase in death from any cause (17.0% vs. 10.5%). On a 3-year adjusted multivariate hazard ratio, the increase was 35% (HR, 1.35; 95% confidence interval, 1.17-1.56; P < .001)

The absolute relative increase in cardiac death was similar in the delayed treatment group (10.8% vs. 6.4%) with a 37% increase in the 3-year multivariate adjustment (HR, 1.37; 95% CI 1.14-1.65; P < .001).
 

Delay raises composite adverse outcome >50%

On a composite of events that included mortality, recurrent MI, or hospitalization for heart failure, the rates climbed from 15.7% in the group treated within 24 hours to 23.3% (P < .001) when treatment was delayed. Heart failure, which was not significantly increased when evaluated separately, was not a major contributor to adverse outcomes, but those with delayed treatment did have more recurrent MIs (5.3% vs. 3.7%; P = .02).

Among a long list of differences between groups, those with delayed care had higher rates of atypical chest pain (25.1% vs. 14.8%; P < .001) and dyspnea (32.6% vs. 23.4%; P < .001). Expressed in odds ratios, they were also significantly more likely to be female (OR, 1.23), be aged 75 years or older (OR, 1.44), have diabetes (OR, 1.31), and to arrive at the hospital without aid from emergency medical services (OR, 3.44).

NSTEMI patients with delayed symptom-to-door time were also less likely to have hypertension (54.8% vs. 59.1%; P < .001), chronic kidney disease (20.8% vs. 25.5%), or a family history of cardiovascular disease (4.7% vs. 7.4%; P < .001). They were more likely to have left main and multivessel disease (57.1% vs. 50.5%; P < .001).

The value of early treatment has already been demonstrated for STEMI, which is reflected in guidelines, most of which now emphasize minimizing the door-to-balloon angioplasty time in order to more rapidly restore perfusion, thereby preserving more functional cardiac tissue. This study suggests that benefit from early intervention is also true of NSTEMI.

Reducing prehospital delay in care “should be emphasized as a crucial factor that increases the risk of all-cause mortality in NSTEMI patients,” reported the authors, led by Jung-Joon Cha, MD, PhD, division of cardiology, Korea University Anam Hospital, Seoul.
 

Public health campaigns needed

When asked about the take-home message, Dr. Cha, along with the senior author, Tae Hoon Ahn, MD, PhD, contend that delays can be addressed by educating both the public and clinicians.

“We would like to emphasize the need for public health campaigns to make patients more aware of atypical symptoms,” Dr. Cha said in an interview.

Dr. Ahn also believes that there is not enough current emphasis within medical systems to recognize and urgently treat NSTEMI patients with a nontraditional profile.

“Atypical symptoms in NSTEMI patients may lead physicians to underestimate the disease severity,” according to Dr. Ahn, who participated in an interview on the significance of these results. He said that atypical symptoms should induce clinicians to exercise “more caution rather than to neglect them.”

For understanding the value of prompt care in NSTEMI patients, this is important information. However, the importance of the 24-hour threshold as a discriminator of long-term risk was questioned by José A. Barrabés, MD, PhD, head of the acute cardiac care unit, University Hospital Vall d’Hebron, Barcelona.

The cutoff in this study was 24 hours, but Dr. Barrabés in an accompanying editorial pointed out that the median delay in those with a symptom-to-door time of at least 24 hours was in fact 72.0 hours.
 

Intermediate delay effect unknown

“This time lag is unusual and reduces the generalizability of the results,” according to Dr. Barrabés. He suggested that the exceptional delay increases the likelihood that the characteristics of the patients, such as more comorbidities or lower socioeconomic status, might have played a role in the differences in outcomes.

Asked to elaborate, Dr. Barrabés explained that delays in treatment, such as antithrombotic therapy, are plausible explanations for the worse outcomes at 3 years, but it is unclear from this data whether the risk starts at a delay of 24 hours.

“It is certainly plausible that intermediate delays are also associated with a worse prognosis,” Dr. Barrabés said in an interview, but “the risk associated with an intermediate delay in symptom-to-door time cannot be quantified with the data collected in this study.”

Dr. Cha and coinvestigators reported no potential conflicts of interest for this study. Dr. Barrabés has financial relationship with AstraZeneca, Novo Nordisk, and Rovi.

Patients who do not receive care for non–ST-segment elevation myocardial infarction (NSTEMI) within 24 hours have a substantially increased risk of mortality 3 years later when compared with those receiving earlier intervention, according to a population-based study evaluating more than 6,000 patients.

The characteristics of patients receiving NSTEMI care more than 24 hours after symptom onset were different from those treated earlier, but understanding these differences might provide clues for improved pathways to care, according to the investigators of this study, published in the Journal of the American College of Cardiology.

In a study of 6,544 NSTEMI patients in the Korea Acute Myocardial Infarction Registry, 1,827 (27%) were evaluated and treated 24 hours or more after symptom onset. When compared with the group with a shorter symptom-to-door time, outcomes at a median follow-up of 1,098 days were substantially worse.

Most importantly, this included a more than 50% absolute unadjusted increase in death from any cause (17.0% vs. 10.5%). On a 3-year adjusted multivariate hazard ratio, the increase was 35% (HR, 1.35; 95% confidence interval, 1.17-1.56; P < .001)

The absolute relative increase in cardiac death was similar in the delayed treatment group (10.8% vs. 6.4%) with a 37% increase in the 3-year multivariate adjustment (HR, 1.37; 95% CI 1.14-1.65; P < .001).
 

Delay raises composite adverse outcome >50%

On a composite of events that included mortality, recurrent MI, or hospitalization for heart failure, the rates climbed from 15.7% in the group treated within 24 hours to 23.3% (P < .001) when treatment was delayed. Heart failure, which was not significantly increased when evaluated separately, was not a major contributor to adverse outcomes, but those with delayed treatment did have more recurrent MIs (5.3% vs. 3.7%; P = .02).

Among a long list of differences between groups, those with delayed care had higher rates of atypical chest pain (25.1% vs. 14.8%; P < .001) and dyspnea (32.6% vs. 23.4%; P < .001). Expressed in odds ratios, they were also significantly more likely to be female (OR, 1.23), be aged 75 years or older (OR, 1.44), have diabetes (OR, 1.31), and to arrive at the hospital without aid from emergency medical services (OR, 3.44).

NSTEMI patients with delayed symptom-to-door time were also less likely to have hypertension (54.8% vs. 59.1%; P < .001), chronic kidney disease (20.8% vs. 25.5%), or a family history of cardiovascular disease (4.7% vs. 7.4%; P < .001). They were more likely to have left main and multivessel disease (57.1% vs. 50.5%; P < .001).

The value of early treatment has already been demonstrated for STEMI, which is reflected in guidelines, most of which now emphasize minimizing the door-to-balloon angioplasty time in order to more rapidly restore perfusion, thereby preserving more functional cardiac tissue. This study suggests that benefit from early intervention is also true of NSTEMI.

Reducing prehospital delay in care “should be emphasized as a crucial factor that increases the risk of all-cause mortality in NSTEMI patients,” reported the authors, led by Jung-Joon Cha, MD, PhD, division of cardiology, Korea University Anam Hospital, Seoul.
 

Public health campaigns needed

When asked about the take-home message, Dr. Cha, along with the senior author, Tae Hoon Ahn, MD, PhD, contend that delays can be addressed by educating both the public and clinicians.

“We would like to emphasize the need for public health campaigns to make patients more aware of atypical symptoms,” Dr. Cha said in an interview.

Dr. Ahn also believes that there is not enough current emphasis within medical systems to recognize and urgently treat NSTEMI patients with a nontraditional profile.

“Atypical symptoms in NSTEMI patients may lead physicians to underestimate the disease severity,” according to Dr. Ahn, who participated in an interview on the significance of these results. He said that atypical symptoms should induce clinicians to exercise “more caution rather than to neglect them.”

For understanding the value of prompt care in NSTEMI patients, this is important information. However, the importance of the 24-hour threshold as a discriminator of long-term risk was questioned by José A. Barrabés, MD, PhD, head of the acute cardiac care unit, University Hospital Vall d’Hebron, Barcelona.

The cutoff in this study was 24 hours, but Dr. Barrabés in an accompanying editorial pointed out that the median delay in those with a symptom-to-door time of at least 24 hours was in fact 72.0 hours.
 

Intermediate delay effect unknown

“This time lag is unusual and reduces the generalizability of the results,” according to Dr. Barrabés. He suggested that the exceptional delay increases the likelihood that the characteristics of the patients, such as more comorbidities or lower socioeconomic status, might have played a role in the differences in outcomes.

Asked to elaborate, Dr. Barrabés explained that delays in treatment, such as antithrombotic therapy, are plausible explanations for the worse outcomes at 3 years, but it is unclear from this data whether the risk starts at a delay of 24 hours.

“It is certainly plausible that intermediate delays are also associated with a worse prognosis,” Dr. Barrabés said in an interview, but “the risk associated with an intermediate delay in symptom-to-door time cannot be quantified with the data collected in this study.”

Dr. Cha and coinvestigators reported no potential conflicts of interest for this study. Dr. Barrabés has financial relationship with AstraZeneca, Novo Nordisk, and Rovi.

Patients who do not receive care for non–ST-segment elevation myocardial infarction (NSTEMI) within 24 hours have a substantially increased risk of mortality 3 years later when compared with those receiving earlier intervention, according to a population-based study evaluating more than 6,000 patients.

The characteristics of patients receiving NSTEMI care more than 24 hours after symptom onset were different from those treated earlier, but understanding these differences might provide clues for improved pathways to care, according to the investigators of this study, published in the Journal of the American College of Cardiology.

In a study of 6,544 NSTEMI patients in the Korea Acute Myocardial Infarction Registry, 1,827 (27%) were evaluated and treated 24 hours or more after symptom onset. When compared with the group with a shorter symptom-to-door time, outcomes at a median follow-up of 1,098 days were substantially worse.

Most importantly, this included a more than 50% absolute unadjusted increase in death from any cause (17.0% vs. 10.5%). On a 3-year adjusted multivariate hazard ratio, the increase was 35% (HR, 1.35; 95% confidence interval, 1.17-1.56; P < .001)

The absolute relative increase in cardiac death was similar in the delayed treatment group (10.8% vs. 6.4%) with a 37% increase in the 3-year multivariate adjustment (HR, 1.37; 95% CI 1.14-1.65; P < .001).
 

Delay raises composite adverse outcome >50%

On a composite of events that included mortality, recurrent MI, or hospitalization for heart failure, the rates climbed from 15.7% in the group treated within 24 hours to 23.3% (P < .001) when treatment was delayed. Heart failure, which was not significantly increased when evaluated separately, was not a major contributor to adverse outcomes, but those with delayed treatment did have more recurrent MIs (5.3% vs. 3.7%; P = .02).

Among a long list of differences between groups, those with delayed care had higher rates of atypical chest pain (25.1% vs. 14.8%; P < .001) and dyspnea (32.6% vs. 23.4%; P < .001). Expressed in odds ratios, they were also significantly more likely to be female (OR, 1.23), be aged 75 years or older (OR, 1.44), have diabetes (OR, 1.31), and to arrive at the hospital without aid from emergency medical services (OR, 3.44).

NSTEMI patients with delayed symptom-to-door time were also less likely to have hypertension (54.8% vs. 59.1%; P < .001), chronic kidney disease (20.8% vs. 25.5%), or a family history of cardiovascular disease (4.7% vs. 7.4%; P < .001). They were more likely to have left main and multivessel disease (57.1% vs. 50.5%; P < .001).

The value of early treatment has already been demonstrated for STEMI, which is reflected in guidelines, most of which now emphasize minimizing the door-to-balloon angioplasty time in order to more rapidly restore perfusion, thereby preserving more functional cardiac tissue. This study suggests that benefit from early intervention is also true of NSTEMI.

Reducing prehospital delay in care “should be emphasized as a crucial factor that increases the risk of all-cause mortality in NSTEMI patients,” reported the authors, led by Jung-Joon Cha, MD, PhD, division of cardiology, Korea University Anam Hospital, Seoul.
 

Public health campaigns needed

When asked about the take-home message, Dr. Cha, along with the senior author, Tae Hoon Ahn, MD, PhD, contend that delays can be addressed by educating both the public and clinicians.

“We would like to emphasize the need for public health campaigns to make patients more aware of atypical symptoms,” Dr. Cha said in an interview.

Dr. Ahn also believes that there is not enough current emphasis within medical systems to recognize and urgently treat NSTEMI patients with a nontraditional profile.

“Atypical symptoms in NSTEMI patients may lead physicians to underestimate the disease severity,” according to Dr. Ahn, who participated in an interview on the significance of these results. He said that atypical symptoms should induce clinicians to exercise “more caution rather than to neglect them.”

For understanding the value of prompt care in NSTEMI patients, this is important information. However, the importance of the 24-hour threshold as a discriminator of long-term risk was questioned by José A. Barrabés, MD, PhD, head of the acute cardiac care unit, University Hospital Vall d’Hebron, Barcelona.

The cutoff in this study was 24 hours, but Dr. Barrabés in an accompanying editorial pointed out that the median delay in those with a symptom-to-door time of at least 24 hours was in fact 72.0 hours.
 

Intermediate delay effect unknown

“This time lag is unusual and reduces the generalizability of the results,” according to Dr. Barrabés. He suggested that the exceptional delay increases the likelihood that the characteristics of the patients, such as more comorbidities or lower socioeconomic status, might have played a role in the differences in outcomes.

Asked to elaborate, Dr. Barrabés explained that delays in treatment, such as antithrombotic therapy, are plausible explanations for the worse outcomes at 3 years, but it is unclear from this data whether the risk starts at a delay of 24 hours.

“It is certainly plausible that intermediate delays are also associated with a worse prognosis,” Dr. Barrabés said in an interview, but “the risk associated with an intermediate delay in symptom-to-door time cannot be quantified with the data collected in this study.”

Dr. Cha and coinvestigators reported no potential conflicts of interest for this study. Dr. Barrabés has financial relationship with AstraZeneca, Novo Nordisk, and Rovi.

BUENOS AIRES – The Latin American Association of Cardiac and Endovascular Surgery (LACES) has demanded “urgent reconsideration” of the decision to downgrade the strength of the recommendation for revascularization or coronary artery bypass graft (CABG) surgery for multivessel disease in the new guideline on coronary artery revascularization, putting it in the same class as the recommendation for percutaneous coronary intervention, which has no apparent advantage over optimal medical therapy.

With the prevalence of stable ischemic heart disease in patients with multivessel disease, the contradiction between the evidence and the new recommendation “may affect the lives and survival of millions of patients worldwide and have a major socio-economic impact,” the association warned in a public letter.

In the 2011 guideline, CABG for patients with multivessel coronary artery disease was given a class I recommendation, which means that it is considered useful and effective and should be performed in the majority of patients in most circumstances. But the new, much weaker class IIb recommendation suggests that the benefit only marginally exceeds the risk and that it should be used selectively and only after careful consideration.

“It is an incomprehensible rollercoaster drop in the recommendation level. We totally disagree. In the absence of evidence, a IIb level provides equal freedom to send a patient to surgery or not. And in patients who are not being sent to surgery, it could take years of survival before we can be sure that we are doing the right thing,” said LACES president Víctor Dayan, MD, PhD, from the cardiovascular center at the Hospital de Clínicas “Dr. Manuel Quintela”, which is part of the School of Medicine at the University of the Republic, Montevideo, Uruguay.

The change in the recommendation for this indication “reflects new evidence showing no advantage of coronary artery bypass grafting over medical therapy alone to improve survival in patients with three-vessel coronary disease with preserved left ventricular function and no left main disease,” according to the authors of the guideline, issued jointly by the American College of Cardiology (ACC), the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI). In particular, they cite the 2019 ISCHEMIA clinical study that failed to show that an early invasive strategy reduces major adverse cardiovascular events, compared with optimal medical therapy and a handful of meta-analyses.

However, ISCHEMIA did not discriminate between the two types of invasive strategy – CABG and percutaneous coronary intervention (PCI) – so cannot be considered as a basis to downgrade the CABG recommendation, Dr. Dayan explained.

“Furthermore, the authors neglected previous RCTs that have shown the survival benefit of CABG in these patients and decided to put PCI in the same [class of recommendation], although no RCT has been able to show any survival advantage of PCI compared to optimal medical treatment,” the LACES letter states.

Basis should be evidence, ‘not inferences’

Three large randomized clinical trials and a 1994 meta-analysis with individual patient data from seven studies firmly established that survival is better with CABG than with medical treatment, the letter continues. However, the guideline authors did not provide any additional randomized clinical trials that refute this evidence.

“Furthermore, the committee disregarded data from the Ten-Year Follow-up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II) randomized control[led] trial, which showed a lower incidence of cardiac mortality (as part of its secondary outcomes) following CABG compared to optimal medical therapy and PCI,” the letter explains.

The guideline authors might have judged current optimal medical therapy to be better than what existed 10, 15, or 30 years ago, diluting the relative benefits of surgery, but the “recommendation in a guideline must act on evidence, not inferences. And there is no evidence to support this drop in recommendation class,” Dr. Dayan said.

Other experts have drawn attention to the fact that two surgical societies – the American Association for Thoracic Surgery (AAST) and the Society of Thoracic Surgeons (STS) – did not endorse the final document, despite having participated in its review, reported this news organization.

“This is a very disappointing update that will negatively affect the lives of many people,” tweeted Marc Pelletier, MD, head of cardiac surgery at University Hospitals, Case Western Reserve University, Cleveland.

Contradictions in the text that examines the evidence and the final recommendations, are “unclear” and “open to various interpretations, when they should be a pillar for decisionmaking,” said Javier Ferrari Ayarragaray, MD, president of the Argentine College of Cardiovascular Surgeons (CACCV) and vice president of LACES.

The new guidelines “show no additional randomized controlled trial to support this downgrade in the level of evidence,” according to a recent CACCV statement. “The inclusion, approval and endorsement of this type of [recommendation,] including [other] international surgical scientific societies, such as STS, AATS, EACTS, LACES[,] is necessary to obtain a better understanding and agreement on the current evidence.”

In a Dec. 17, 2021 response to LACES, Patrick O’Gara, MD, who was chair of the ACC/AHA Joint Committee on Clinical Practice Guidelines at the time, and his successor, Joshua Beckman, MD, explained that both organizations approved the guideline for publication and support its authors “in their interpretation of the published evidence and findings.”

The pair pointed out that the drafting committee members, who have extensive clinical judgment and experience, deliberated extensively on the issue and that the change from a class I to a class IIb recommendation was “carefully considered after a review of the entire available and relevant evidence.”

“When we bring together multiple organizations to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of published and peer-reviewed literature and create clinical practice recommendations,” said Thomas Getchius, director of guideline strategy and operations at the AHA.

“The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed upon by the ACC, AHA, SCAI, and the full drafting committee,” Mr. Getchius said.

Dr. Dayan and Dr. Ferrari Ayarragaray have disclosed no relevant financial relationships. Mr. Getchius is an employee of the American Heart Association.

A version of this article first appeared on Medscape.com.

BUENOS AIRES – The Latin American Association of Cardiac and Endovascular Surgery (LACES) has demanded “urgent reconsideration” of the decision to downgrade the strength of the recommendation for revascularization or coronary artery bypass graft (CABG) surgery for multivessel disease in the new guideline on coronary artery revascularization, putting it in the same class as the recommendation for percutaneous coronary intervention, which has no apparent advantage over optimal medical therapy.

With the prevalence of stable ischemic heart disease in patients with multivessel disease, the contradiction between the evidence and the new recommendation “may affect the lives and survival of millions of patients worldwide and have a major socio-economic impact,” the association warned in a public letter.

In the 2011 guideline, CABG for patients with multivessel coronary artery disease was given a class I recommendation, which means that it is considered useful and effective and should be performed in the majority of patients in most circumstances. But the new, much weaker class IIb recommendation suggests that the benefit only marginally exceeds the risk and that it should be used selectively and only after careful consideration.

“It is an incomprehensible rollercoaster drop in the recommendation level. We totally disagree. In the absence of evidence, a IIb level provides equal freedom to send a patient to surgery or not. And in patients who are not being sent to surgery, it could take years of survival before we can be sure that we are doing the right thing,” said LACES president Víctor Dayan, MD, PhD, from the cardiovascular center at the Hospital de Clínicas “Dr. Manuel Quintela”, which is part of the School of Medicine at the University of the Republic, Montevideo, Uruguay.

The change in the recommendation for this indication “reflects new evidence showing no advantage of coronary artery bypass grafting over medical therapy alone to improve survival in patients with three-vessel coronary disease with preserved left ventricular function and no left main disease,” according to the authors of the guideline, issued jointly by the American College of Cardiology (ACC), the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI). In particular, they cite the 2019 ISCHEMIA clinical study that failed to show that an early invasive strategy reduces major adverse cardiovascular events, compared with optimal medical therapy and a handful of meta-analyses.

However, ISCHEMIA did not discriminate between the two types of invasive strategy – CABG and percutaneous coronary intervention (PCI) – so cannot be considered as a basis to downgrade the CABG recommendation, Dr. Dayan explained.

“Furthermore, the authors neglected previous RCTs that have shown the survival benefit of CABG in these patients and decided to put PCI in the same [class of recommendation], although no RCT has been able to show any survival advantage of PCI compared to optimal medical treatment,” the LACES letter states.

Basis should be evidence, ‘not inferences’

Three large randomized clinical trials and a 1994 meta-analysis with individual patient data from seven studies firmly established that survival is better with CABG than with medical treatment, the letter continues. However, the guideline authors did not provide any additional randomized clinical trials that refute this evidence.

“Furthermore, the committee disregarded data from the Ten-Year Follow-up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II) randomized control[led] trial, which showed a lower incidence of cardiac mortality (as part of its secondary outcomes) following CABG compared to optimal medical therapy and PCI,” the letter explains.

The guideline authors might have judged current optimal medical therapy to be better than what existed 10, 15, or 30 years ago, diluting the relative benefits of surgery, but the “recommendation in a guideline must act on evidence, not inferences. And there is no evidence to support this drop in recommendation class,” Dr. Dayan said.

Other experts have drawn attention to the fact that two surgical societies – the American Association for Thoracic Surgery (AAST) and the Society of Thoracic Surgeons (STS) – did not endorse the final document, despite having participated in its review, reported this news organization.

“This is a very disappointing update that will negatively affect the lives of many people,” tweeted Marc Pelletier, MD, head of cardiac surgery at University Hospitals, Case Western Reserve University, Cleveland.

Contradictions in the text that examines the evidence and the final recommendations, are “unclear” and “open to various interpretations, when they should be a pillar for decisionmaking,” said Javier Ferrari Ayarragaray, MD, president of the Argentine College of Cardiovascular Surgeons (CACCV) and vice president of LACES.

The new guidelines “show no additional randomized controlled trial to support this downgrade in the level of evidence,” according to a recent CACCV statement. “The inclusion, approval and endorsement of this type of [recommendation,] including [other] international surgical scientific societies, such as STS, AATS, EACTS, LACES[,] is necessary to obtain a better understanding and agreement on the current evidence.”

In a Dec. 17, 2021 response to LACES, Patrick O’Gara, MD, who was chair of the ACC/AHA Joint Committee on Clinical Practice Guidelines at the time, and his successor, Joshua Beckman, MD, explained that both organizations approved the guideline for publication and support its authors “in their interpretation of the published evidence and findings.”

The pair pointed out that the drafting committee members, who have extensive clinical judgment and experience, deliberated extensively on the issue and that the change from a class I to a class IIb recommendation was “carefully considered after a review of the entire available and relevant evidence.”

“When we bring together multiple organizations to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of published and peer-reviewed literature and create clinical practice recommendations,” said Thomas Getchius, director of guideline strategy and operations at the AHA.

“The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed upon by the ACC, AHA, SCAI, and the full drafting committee,” Mr. Getchius said.

Dr. Dayan and Dr. Ferrari Ayarragaray have disclosed no relevant financial relationships. Mr. Getchius is an employee of the American Heart Association.

A version of this article first appeared on Medscape.com.

BUENOS AIRES – The Latin American Association of Cardiac and Endovascular Surgery (LACES) has demanded “urgent reconsideration” of the decision to downgrade the strength of the recommendation for revascularization or coronary artery bypass graft (CABG) surgery for multivessel disease in the new guideline on coronary artery revascularization, putting it in the same class as the recommendation for percutaneous coronary intervention, which has no apparent advantage over optimal medical therapy.

With the prevalence of stable ischemic heart disease in patients with multivessel disease, the contradiction between the evidence and the new recommendation “may affect the lives and survival of millions of patients worldwide and have a major socio-economic impact,” the association warned in a public letter.

In the 2011 guideline, CABG for patients with multivessel coronary artery disease was given a class I recommendation, which means that it is considered useful and effective and should be performed in the majority of patients in most circumstances. But the new, much weaker class IIb recommendation suggests that the benefit only marginally exceeds the risk and that it should be used selectively and only after careful consideration.

“It is an incomprehensible rollercoaster drop in the recommendation level. We totally disagree. In the absence of evidence, a IIb level provides equal freedom to send a patient to surgery or not. And in patients who are not being sent to surgery, it could take years of survival before we can be sure that we are doing the right thing,” said LACES president Víctor Dayan, MD, PhD, from the cardiovascular center at the Hospital de Clínicas “Dr. Manuel Quintela”, which is part of the School of Medicine at the University of the Republic, Montevideo, Uruguay.

The change in the recommendation for this indication “reflects new evidence showing no advantage of coronary artery bypass grafting over medical therapy alone to improve survival in patients with three-vessel coronary disease with preserved left ventricular function and no left main disease,” according to the authors of the guideline, issued jointly by the American College of Cardiology (ACC), the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI). In particular, they cite the 2019 ISCHEMIA clinical study that failed to show that an early invasive strategy reduces major adverse cardiovascular events, compared with optimal medical therapy and a handful of meta-analyses.

However, ISCHEMIA did not discriminate between the two types of invasive strategy – CABG and percutaneous coronary intervention (PCI) – so cannot be considered as a basis to downgrade the CABG recommendation, Dr. Dayan explained.

“Furthermore, the authors neglected previous RCTs that have shown the survival benefit of CABG in these patients and decided to put PCI in the same [class of recommendation], although no RCT has been able to show any survival advantage of PCI compared to optimal medical treatment,” the LACES letter states.

Basis should be evidence, ‘not inferences’

Three large randomized clinical trials and a 1994 meta-analysis with individual patient data from seven studies firmly established that survival is better with CABG than with medical treatment, the letter continues. However, the guideline authors did not provide any additional randomized clinical trials that refute this evidence.

“Furthermore, the committee disregarded data from the Ten-Year Follow-up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II) randomized control[led] trial, which showed a lower incidence of cardiac mortality (as part of its secondary outcomes) following CABG compared to optimal medical therapy and PCI,” the letter explains.

The guideline authors might have judged current optimal medical therapy to be better than what existed 10, 15, or 30 years ago, diluting the relative benefits of surgery, but the “recommendation in a guideline must act on evidence, not inferences. And there is no evidence to support this drop in recommendation class,” Dr. Dayan said.

Other experts have drawn attention to the fact that two surgical societies – the American Association for Thoracic Surgery (AAST) and the Society of Thoracic Surgeons (STS) – did not endorse the final document, despite having participated in its review, reported this news organization.

“This is a very disappointing update that will negatively affect the lives of many people,” tweeted Marc Pelletier, MD, head of cardiac surgery at University Hospitals, Case Western Reserve University, Cleveland.

Contradictions in the text that examines the evidence and the final recommendations, are “unclear” and “open to various interpretations, when they should be a pillar for decisionmaking,” said Javier Ferrari Ayarragaray, MD, president of the Argentine College of Cardiovascular Surgeons (CACCV) and vice president of LACES.

The new guidelines “show no additional randomized controlled trial to support this downgrade in the level of evidence,” according to a recent CACCV statement. “The inclusion, approval and endorsement of this type of [recommendation,] including [other] international surgical scientific societies, such as STS, AATS, EACTS, LACES[,] is necessary to obtain a better understanding and agreement on the current evidence.”

In a Dec. 17, 2021 response to LACES, Patrick O’Gara, MD, who was chair of the ACC/AHA Joint Committee on Clinical Practice Guidelines at the time, and his successor, Joshua Beckman, MD, explained that both organizations approved the guideline for publication and support its authors “in their interpretation of the published evidence and findings.”

The pair pointed out that the drafting committee members, who have extensive clinical judgment and experience, deliberated extensively on the issue and that the change from a class I to a class IIb recommendation was “carefully considered after a review of the entire available and relevant evidence.”

“When we bring together multiple organizations to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of published and peer-reviewed literature and create clinical practice recommendations,” said Thomas Getchius, director of guideline strategy and operations at the AHA.

“The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed upon by the ACC, AHA, SCAI, and the full drafting committee,” Mr. Getchius said.

Dr. Dayan and Dr. Ferrari Ayarragaray have disclosed no relevant financial relationships. Mr. Getchius is an employee of the American Heart Association.

A version of this article first appeared on Medscape.com.

Patients looking to refill a prescription for apixaban (Eliquis) through CVS Caremark may be in for a surprise following its decision to exclude the direct oral anticoagulant (DOAC) from its formulary starting Jan. 1.

The move leaves just one DOAC, rivaroxaban (Xarelto), on CVS’ commercial formulary and is being assailed as the latest example of “nonmedical switching” used by health insurers to control costs.

In a letter to CVS Caremark backed by 14 provider and patient organizations, the nonprofit Partnership to Advance Cardiovascular Health (PACH) calls on the pharmacy chain to reverse its “dangerously disruptive” decision to force stable patients at high risk of cardiovascular events to switch anticoagulation, without an apparent option to be grandfathered into the new plan.

PACH president Dharmesh Patel, MD, Stern Cardiovascular Center, Memphis, called the formulary change “reckless and irresponsible, especially because the decision is not based in science and evidence, but on budgets. Patients and their health care providers, not insurance companies, need to be trusted to determine what medication is best,” he said in a statement.

Craig Beavers, PharmD, vice president of Baptist Health Paducah, Kentucky, said that, as chair of the American College of Cardiology’s Cardiovascular Team Section, he and other organizations have met with CVS Caremark medical leadership to advocate for patients and to understand the company’s perspective.

“The underlying driver is cost,” he told this news organization.

Current guidelines recommend DOACs in general for a variety of indications, including to reduce the risk of stroke and embolism in nonvalvular atrial fibrillation and to prevent deep vein thrombosis, but there are select instances where a particular DOAC might be more appropriate, he observed.

“Apixaban may be better for a patient with a history of GI bleeding because there’s less GI bleeding, but the guidelines don’t necessarily spell those things out,” Dr. Beavers said. “That’s where the clinician should advocate for their patient and, unfortunately, they are making their decision strictly based off the guidelines.”

Requests to speak with medical officers at CVS Caremark went unanswered, but its executive director of communications, Christina Peaslee, told this news organization that the formulary decision “maintains clinically appropriate, cost-effective prescription coverage” for its clients and members.

“Both the American Heart Association/American College of Cardiology/Heart Rhythm Society and 2021 CHEST guidelines recommend DOACs over warfarin for treatment of various cardiology conditions such as atrial fibrillation, but neither list a specific agent as preferred – showing that consensus clinical guidelines do not favor one over the other,” she said in an email. “Further, Xarelto has more FDA-approved indications than Eliquis (e.g., Xarelto is approved for a reduction in risk of major CV events in patients with CAD or PAD) in addition to all the same FDA indications as Eliquis.”

Ms. Peaslee pointed out that all formulary changes are evaluated by an external medical expert specializing in the disease state, followed by review and approval by an independent national Pharmacy & Therapeutics Committee.

The decision to exclude apixaban is also limited to a “subset of commercial drug lists,” she said, although specifics on which plans and the number of affected patients were not forthcoming.

The choice of DOAC is a timely question in cardiology, with recent studies suggesting an advantage for apixaban over rivaroxaban in reducing the risk of recurrent venous thromboembolism, as well as reducing the risk of major ischemic or hemorrhagic events in atrial fibrillation.

Ms. Peaslee said CVS Caremark closely monitors medical literature for relevant clinical trial data and that most clients allow reasonable formulary exceptions when justified. “This formulary exceptions process has been successfully used for changes of this type and allows patients to get a medication that is safe and effective, as determined by their prescriber.”

The company will also continue to provide “robust, personalized outreach to the small number of members who will need to switch to an alternative medication,” she added.

Dr. Beavers said negotiations with CVS are still in the early stages, but, in the meantime, the ACC is providing health care providers with tools, such as drug copay cards and electronic prior authorizations, to help ensure patients don’t have gaps in coverage.

In a Jan. 14 news release addressing the formulary change, ACC notes that a patient’s pharmacy can also request a one-time override when trying to fill a nonpreferred DOAC in January to buy time if switching medications with their clinician or requesting a formulary exception.

During discussions with CVS Caremark, it says the ACC and the American Society of Hematology “underscored the negative impacts of this decision on patients currently taking one of the nonpreferred DOACs and on those who have previously tried rivaroxaban and changed medications.”

The groups also highlighted difficulties with other prior authorization programs in terms of the need for dedicated staff and time away from direct patient care.

“The ACC and ASH will continue discussions with CVS Caremark regarding the burden on clinicians and the effect of the formulary decision on patient access,” the release says.

In its letter to CVS, PACH argues that the apixaban exclusion will disproportionately affect historically disadvantaged patients, leaving those who can least afford the change with limited options. Notably, no generic is available for either apixaban or rivaroxaban.

The group also highlights a 2019 national poll, in which nearly 40% of patients who had their medication switched were so frustrated that they stopped their medication altogether.

PACH has an online petition against nonmedical switching, which at press time had garnered 2,126 signatures.

One signee, Jan Griffin, who survived bilateral pulmonary embolisms, writes that she has been on Eliquis [apixaban] successfully since her hospital discharge. “Now, as of midnight, Caremark apparently knows better than my hematologist as to what blood thinner is better for me and will no longer cover my Eliquis prescription. This is criminal, immoral, and unethical. #StopTheSwitch.”

A version of this article first appeared on Medscape.com.

Patients looking to refill a prescription for apixaban (Eliquis) through CVS Caremark may be in for a surprise following its decision to exclude the direct oral anticoagulant (DOAC) from its formulary starting Jan. 1.

The move leaves just one DOAC, rivaroxaban (Xarelto), on CVS’ commercial formulary and is being assailed as the latest example of “nonmedical switching” used by health insurers to control costs.

In a letter to CVS Caremark backed by 14 provider and patient organizations, the nonprofit Partnership to Advance Cardiovascular Health (PACH) calls on the pharmacy chain to reverse its “dangerously disruptive” decision to force stable patients at high risk of cardiovascular events to switch anticoagulation, without an apparent option to be grandfathered into the new plan.

PACH president Dharmesh Patel, MD, Stern Cardiovascular Center, Memphis, called the formulary change “reckless and irresponsible, especially because the decision is not based in science and evidence, but on budgets. Patients and their health care providers, not insurance companies, need to be trusted to determine what medication is best,” he said in a statement.

Craig Beavers, PharmD, vice president of Baptist Health Paducah, Kentucky, said that, as chair of the American College of Cardiology’s Cardiovascular Team Section, he and other organizations have met with CVS Caremark medical leadership to advocate for patients and to understand the company’s perspective.

“The underlying driver is cost,” he told this news organization.

Current guidelines recommend DOACs in general for a variety of indications, including to reduce the risk of stroke and embolism in nonvalvular atrial fibrillation and to prevent deep vein thrombosis, but there are select instances where a particular DOAC might be more appropriate, he observed.

“Apixaban may be better for a patient with a history of GI bleeding because there’s less GI bleeding, but the guidelines don’t necessarily spell those things out,” Dr. Beavers said. “That’s where the clinician should advocate for their patient and, unfortunately, they are making their decision strictly based off the guidelines.”

Requests to speak with medical officers at CVS Caremark went unanswered, but its executive director of communications, Christina Peaslee, told this news organization that the formulary decision “maintains clinically appropriate, cost-effective prescription coverage” for its clients and members.

“Both the American Heart Association/American College of Cardiology/Heart Rhythm Society and 2021 CHEST guidelines recommend DOACs over warfarin for treatment of various cardiology conditions such as atrial fibrillation, but neither list a specific agent as preferred – showing that consensus clinical guidelines do not favor one over the other,” she said in an email. “Further, Xarelto has more FDA-approved indications than Eliquis (e.g., Xarelto is approved for a reduction in risk of major CV events in patients with CAD or PAD) in addition to all the same FDA indications as Eliquis.”

Ms. Peaslee pointed out that all formulary changes are evaluated by an external medical expert specializing in the disease state, followed by review and approval by an independent national Pharmacy & Therapeutics Committee.

The decision to exclude apixaban is also limited to a “subset of commercial drug lists,” she said, although specifics on which plans and the number of affected patients were not forthcoming.

The choice of DOAC is a timely question in cardiology, with recent studies suggesting an advantage for apixaban over rivaroxaban in reducing the risk of recurrent venous thromboembolism, as well as reducing the risk of major ischemic or hemorrhagic events in atrial fibrillation.

Ms. Peaslee said CVS Caremark closely monitors medical literature for relevant clinical trial data and that most clients allow reasonable formulary exceptions when justified. “This formulary exceptions process has been successfully used for changes of this type and allows patients to get a medication that is safe and effective, as determined by their prescriber.”

The company will also continue to provide “robust, personalized outreach to the small number of members who will need to switch to an alternative medication,” she added.

Dr. Beavers said negotiations with CVS are still in the early stages, but, in the meantime, the ACC is providing health care providers with tools, such as drug copay cards and electronic prior authorizations, to help ensure patients don’t have gaps in coverage.

In a Jan. 14 news release addressing the formulary change, ACC notes that a patient’s pharmacy can also request a one-time override when trying to fill a nonpreferred DOAC in January to buy time if switching medications with their clinician or requesting a formulary exception.

During discussions with CVS Caremark, it says the ACC and the American Society of Hematology “underscored the negative impacts of this decision on patients currently taking one of the nonpreferred DOACs and on those who have previously tried rivaroxaban and changed medications.”

The groups also highlighted difficulties with other prior authorization programs in terms of the need for dedicated staff and time away from direct patient care.

“The ACC and ASH will continue discussions with CVS Caremark regarding the burden on clinicians and the effect of the formulary decision on patient access,” the release says.

In its letter to CVS, PACH argues that the apixaban exclusion will disproportionately affect historically disadvantaged patients, leaving those who can least afford the change with limited options. Notably, no generic is available for either apixaban or rivaroxaban.

The group also highlights a 2019 national poll, in which nearly 40% of patients who had their medication switched were so frustrated that they stopped their medication altogether.

PACH has an online petition against nonmedical switching, which at press time had garnered 2,126 signatures.

One signee, Jan Griffin, who survived bilateral pulmonary embolisms, writes that she has been on Eliquis [apixaban] successfully since her hospital discharge. “Now, as of midnight, Caremark apparently knows better than my hematologist as to what blood thinner is better for me and will no longer cover my Eliquis prescription. This is criminal, immoral, and unethical. #StopTheSwitch.”

A version of this article first appeared on Medscape.com.

Patients looking to refill a prescription for apixaban (Eliquis) through CVS Caremark may be in for a surprise following its decision to exclude the direct oral anticoagulant (DOAC) from its formulary starting Jan. 1.

The move leaves just one DOAC, rivaroxaban (Xarelto), on CVS’ commercial formulary and is being assailed as the latest example of “nonmedical switching” used by health insurers to control costs.

In a letter to CVS Caremark backed by 14 provider and patient organizations, the nonprofit Partnership to Advance Cardiovascular Health (PACH) calls on the pharmacy chain to reverse its “dangerously disruptive” decision to force stable patients at high risk of cardiovascular events to switch anticoagulation, without an apparent option to be grandfathered into the new plan.

PACH president Dharmesh Patel, MD, Stern Cardiovascular Center, Memphis, called the formulary change “reckless and irresponsible, especially because the decision is not based in science and evidence, but on budgets. Patients and their health care providers, not insurance companies, need to be trusted to determine what medication is best,” he said in a statement.

Craig Beavers, PharmD, vice president of Baptist Health Paducah, Kentucky, said that, as chair of the American College of Cardiology’s Cardiovascular Team Section, he and other organizations have met with CVS Caremark medical leadership to advocate for patients and to understand the company’s perspective.

“The underlying driver is cost,” he told this news organization.

Current guidelines recommend DOACs in general for a variety of indications, including to reduce the risk of stroke and embolism in nonvalvular atrial fibrillation and to prevent deep vein thrombosis, but there are select instances where a particular DOAC might be more appropriate, he observed.

“Apixaban may be better for a patient with a history of GI bleeding because there’s less GI bleeding, but the guidelines don’t necessarily spell those things out,” Dr. Beavers said. “That’s where the clinician should advocate for their patient and, unfortunately, they are making their decision strictly based off the guidelines.”

Requests to speak with medical officers at CVS Caremark went unanswered, but its executive director of communications, Christina Peaslee, told this news organization that the formulary decision “maintains clinically appropriate, cost-effective prescription coverage” for its clients and members.

“Both the American Heart Association/American College of Cardiology/Heart Rhythm Society and 2021 CHEST guidelines recommend DOACs over warfarin for treatment of various cardiology conditions such as atrial fibrillation, but neither list a specific agent as preferred – showing that consensus clinical guidelines do not favor one over the other,” she said in an email. “Further, Xarelto has more FDA-approved indications than Eliquis (e.g., Xarelto is approved for a reduction in risk of major CV events in patients with CAD or PAD) in addition to all the same FDA indications as Eliquis.”

Ms. Peaslee pointed out that all formulary changes are evaluated by an external medical expert specializing in the disease state, followed by review and approval by an independent national Pharmacy & Therapeutics Committee.

The decision to exclude apixaban is also limited to a “subset of commercial drug lists,” she said, although specifics on which plans and the number of affected patients were not forthcoming.

The choice of DOAC is a timely question in cardiology, with recent studies suggesting an advantage for apixaban over rivaroxaban in reducing the risk of recurrent venous thromboembolism, as well as reducing the risk of major ischemic or hemorrhagic events in atrial fibrillation.

Ms. Peaslee said CVS Caremark closely monitors medical literature for relevant clinical trial data and that most clients allow reasonable formulary exceptions when justified. “This formulary exceptions process has been successfully used for changes of this type and allows patients to get a medication that is safe and effective, as determined by their prescriber.”

The company will also continue to provide “robust, personalized outreach to the small number of members who will need to switch to an alternative medication,” she added.

Dr. Beavers said negotiations with CVS are still in the early stages, but, in the meantime, the ACC is providing health care providers with tools, such as drug copay cards and electronic prior authorizations, to help ensure patients don’t have gaps in coverage.

In a Jan. 14 news release addressing the formulary change, ACC notes that a patient’s pharmacy can also request a one-time override when trying to fill a nonpreferred DOAC in January to buy time if switching medications with their clinician or requesting a formulary exception.

During discussions with CVS Caremark, it says the ACC and the American Society of Hematology “underscored the negative impacts of this decision on patients currently taking one of the nonpreferred DOACs and on those who have previously tried rivaroxaban and changed medications.”

The groups also highlighted difficulties with other prior authorization programs in terms of the need for dedicated staff and time away from direct patient care.

“The ACC and ASH will continue discussions with CVS Caremark regarding the burden on clinicians and the effect of the formulary decision on patient access,” the release says.

In its letter to CVS, PACH argues that the apixaban exclusion will disproportionately affect historically disadvantaged patients, leaving those who can least afford the change with limited options. Notably, no generic is available for either apixaban or rivaroxaban.

The group also highlights a 2019 national poll, in which nearly 40% of patients who had their medication switched were so frustrated that they stopped their medication altogether.

PACH has an online petition against nonmedical switching, which at press time had garnered 2,126 signatures.

One signee, Jan Griffin, who survived bilateral pulmonary embolisms, writes that she has been on Eliquis [apixaban] successfully since her hospital discharge. “Now, as of midnight, Caremark apparently knows better than my hematologist as to what blood thinner is better for me and will no longer cover my Eliquis prescription. This is criminal, immoral, and unethical. #StopTheSwitch.”

A version of this article first appeared on Medscape.com.

Scientific achievements usually raise big new questions, and the remarkable surgery that took place on Jan. 7, when Maryland resident David Bennett was transplanted with a genetically modified heart from a pig, has been no different.

The 57-year-old with end-stage heart failure had been repeatedly turned down for a standard transplant and was judged a poor candidate for a ventricular assist device. Now his new heart is beating soundly and apparently accepted by his immune system as Mr. Bennett, his physicians at the University of Maryland where the procedure took place, and indeed the world set out on a journey with far more unknowns than knowns.

University of Maryland Medical Center

“I think even just a couple of years ago, people felt that xenotransplantation for the heart and other organs was still a long way off. And it seems like it’s started to move very quickly,” Larry A. Allen, MD, University of Colorado, Aurora, said in an interview.

Demand for donor hearts far outstrips supply, and despite advances in the development of ventricular assist pumps and artificial hearts, “there are still significant limitations to them in terms of clotting, stroke, and infection. We’ve seen the use of those devices plateau,” Dr. Allen said. “So, the concept of a nonhuman source of organs is exciting and very much in need, if people can get it to work.”

“I really credit the surgeons at the University of Maryland for courageous clinical work and a brilliant scientific innovation,” Clyde W. Yancy, MD, MSc, Northwestern University, Chicago, said in an interview. “But it’s always in the implementation that we have to hold our breath.” Heart xenotransplantation is an old idea that “has never before been successful,” he said. And standard heart transplantation has set a high bar, with a 1-year survival of about 90% and low 1-year risk for rejection. Whether the new procedure can meet that standard is unknown, as is its potential for complications, such as chronic rejection or cancers due to long-term immunosuppression. Those are “major questions requiring more time and careful follow-up.”

‘Still a nascent technology’

“This is an exciting and courageous step forward in heart transplantation, and kudos to the team at the University of Maryland,” said Mandeep R. Mehra, MD, Brigham and Woman’s Hospital, Boston. But “there are many challenges here.”

University of Maryland Medical Center

The procedure’s 10 gene modifications were reportedly aimed at preventing hyperacute rejection of the heart and its excessive growth after transplantation, and making the organ less immunogenic, Dr. Mehra said in an interview. But even if those goals are met, could the same changes potentially impede the heart’s adaptation to human physiology, such as during ambulation or stress?

That kind of adaptation may become important. For example, Dr. Mehra observed, normally a pig heart “provides flow in a four-footed configuration, and pig temperature is inherently higher than humans by several degrees, so it will be functioning in a relatively hypothermic environment.”

Transplantation remains the gold standard for patients with advanced heart failure despite modern medical and device therapy, Dr. Allen agreed. But “if we can raise pig hearts that provide the organ, and it can be implanted with a surgery that’s been done for 50 years, and rejection can be managed with gene editing and tailored immunosuppression, then it’s not hard to think about this very rapidly replacing a lot of what we do in the advanced heart failure and transplantation world.”

Certainly, it would be a major advance if the gene editing technique successfully improves the heart’s immunologic compatibility, Dr. Yancy noted. But do we have enough genomic knowledge to select gene deletions and insertions in the safest way for a successful outcome? “We have to appreciate that this is still a nascent technology, and we should be careful that there might be consequences that we haven’t anticipated.”

For example, he said, the xenotransplantation and gene-modifying techniques should be explored in a range of patients, including older and younger people, women and men, and people of different ethnicities and races.

“There may be some differences based on ancestry, based on gender, based on aging, that will influence the way in which these engineered donor hearts are experienced clinically,” Dr. Yancy said.

The xenotransplantation technique’s potential impact on health equity should also be considered, as it “almost assuredly will be a very expensive technology that will be utilized in a very select population,” he noted. “We need to have a really wide lens to think about all of the potential ramifications.”
 

‘This field needs to evolve’

Dr. Mehra also flagged the procedure’s potential cost should it become mainstream. Perhaps that would promote dialogue on how to primarily use it “after legitimately exhausting all available options, such as total artificial heart support.”

It might also teach the field to take greater advantage of the many donated hearts discarded as suboptimal. “The general usage rate for offered organs is around a third,” despite opportunities to expand use of those that are “less than perfect,” Dr. Mehra said. “I think that the field will grow with the community focusing on reduced discards of current available heart organs, and not necessarily grow because of the availability of ‘xeno-organs.’ ”

“This field needs to evolve because we’re actively transplanting patients today. But in my mind, the real future is to have such a sufficient understanding of the biology of left ventricular dysfunction that transplantation is a rare event,” Dr. Yancy proposed.

“I’m not certain that heart transplantation per se is the endgame. I think the avoidance of transplantation is the real endgame,” he said. “This may be controversial, but my vision of the future is not one where we have a supply of animals that we can use for transplantation. My vision of the future is that heart transplantation becomes obsolete.”

A version of this article first appeared on Medscape.com.

Scientific achievements usually raise big new questions, and the remarkable surgery that took place on Jan. 7, when Maryland resident David Bennett was transplanted with a genetically modified heart from a pig, has been no different.

The 57-year-old with end-stage heart failure had been repeatedly turned down for a standard transplant and was judged a poor candidate for a ventricular assist device. Now his new heart is beating soundly and apparently accepted by his immune system as Mr. Bennett, his physicians at the University of Maryland where the procedure took place, and indeed the world set out on a journey with far more unknowns than knowns.

University of Maryland Medical Center

“I think even just a couple of years ago, people felt that xenotransplantation for the heart and other organs was still a long way off. And it seems like it’s started to move very quickly,” Larry A. Allen, MD, University of Colorado, Aurora, said in an interview.

Demand for donor hearts far outstrips supply, and despite advances in the development of ventricular assist pumps and artificial hearts, “there are still significant limitations to them in terms of clotting, stroke, and infection. We’ve seen the use of those devices plateau,” Dr. Allen said. “So, the concept of a nonhuman source of organs is exciting and very much in need, if people can get it to work.”

“I really credit the surgeons at the University of Maryland for courageous clinical work and a brilliant scientific innovation,” Clyde W. Yancy, MD, MSc, Northwestern University, Chicago, said in an interview. “But it’s always in the implementation that we have to hold our breath.” Heart xenotransplantation is an old idea that “has never before been successful,” he said. And standard heart transplantation has set a high bar, with a 1-year survival of about 90% and low 1-year risk for rejection. Whether the new procedure can meet that standard is unknown, as is its potential for complications, such as chronic rejection or cancers due to long-term immunosuppression. Those are “major questions requiring more time and careful follow-up.”

‘Still a nascent technology’

“This is an exciting and courageous step forward in heart transplantation, and kudos to the team at the University of Maryland,” said Mandeep R. Mehra, MD, Brigham and Woman’s Hospital, Boston. But “there are many challenges here.”

University of Maryland Medical Center

The procedure’s 10 gene modifications were reportedly aimed at preventing hyperacute rejection of the heart and its excessive growth after transplantation, and making the organ less immunogenic, Dr. Mehra said in an interview. But even if those goals are met, could the same changes potentially impede the heart’s adaptation to human physiology, such as during ambulation or stress?

That kind of adaptation may become important. For example, Dr. Mehra observed, normally a pig heart “provides flow in a four-footed configuration, and pig temperature is inherently higher than humans by several degrees, so it will be functioning in a relatively hypothermic environment.”

Transplantation remains the gold standard for patients with advanced heart failure despite modern medical and device therapy, Dr. Allen agreed. But “if we can raise pig hearts that provide the organ, and it can be implanted with a surgery that’s been done for 50 years, and rejection can be managed with gene editing and tailored immunosuppression, then it’s not hard to think about this very rapidly replacing a lot of what we do in the advanced heart failure and transplantation world.”

Certainly, it would be a major advance if the gene editing technique successfully improves the heart’s immunologic compatibility, Dr. Yancy noted. But do we have enough genomic knowledge to select gene deletions and insertions in the safest way for a successful outcome? “We have to appreciate that this is still a nascent technology, and we should be careful that there might be consequences that we haven’t anticipated.”

For example, he said, the xenotransplantation and gene-modifying techniques should be explored in a range of patients, including older and younger people, women and men, and people of different ethnicities and races.

“There may be some differences based on ancestry, based on gender, based on aging, that will influence the way in which these engineered donor hearts are experienced clinically,” Dr. Yancy said.

The xenotransplantation technique’s potential impact on health equity should also be considered, as it “almost assuredly will be a very expensive technology that will be utilized in a very select population,” he noted. “We need to have a really wide lens to think about all of the potential ramifications.”
 

‘This field needs to evolve’

Dr. Mehra also flagged the procedure’s potential cost should it become mainstream. Perhaps that would promote dialogue on how to primarily use it “after legitimately exhausting all available options, such as total artificial heart support.”

It might also teach the field to take greater advantage of the many donated hearts discarded as suboptimal. “The general usage rate for offered organs is around a third,” despite opportunities to expand use of those that are “less than perfect,” Dr. Mehra said. “I think that the field will grow with the community focusing on reduced discards of current available heart organs, and not necessarily grow because of the availability of ‘xeno-organs.’ ”

“This field needs to evolve because we’re actively transplanting patients today. But in my mind, the real future is to have such a sufficient understanding of the biology of left ventricular dysfunction that transplantation is a rare event,” Dr. Yancy proposed.

“I’m not certain that heart transplantation per se is the endgame. I think the avoidance of transplantation is the real endgame,” he said. “This may be controversial, but my vision of the future is not one where we have a supply of animals that we can use for transplantation. My vision of the future is that heart transplantation becomes obsolete.”

A version of this article first appeared on Medscape.com.

Scientific achievements usually raise big new questions, and the remarkable surgery that took place on Jan. 7, when Maryland resident David Bennett was transplanted with a genetically modified heart from a pig, has been no different.

The 57-year-old with end-stage heart failure had been repeatedly turned down for a standard transplant and was judged a poor candidate for a ventricular assist device. Now his new heart is beating soundly and apparently accepted by his immune system as Mr. Bennett, his physicians at the University of Maryland where the procedure took place, and indeed the world set out on a journey with far more unknowns than knowns.

University of Maryland Medical Center

“I think even just a couple of years ago, people felt that xenotransplantation for the heart and other organs was still a long way off. And it seems like it’s started to move very quickly,” Larry A. Allen, MD, University of Colorado, Aurora, said in an interview.

Demand for donor hearts far outstrips supply, and despite advances in the development of ventricular assist pumps and artificial hearts, “there are still significant limitations to them in terms of clotting, stroke, and infection. We’ve seen the use of those devices plateau,” Dr. Allen said. “So, the concept of a nonhuman source of organs is exciting and very much in need, if people can get it to work.”

“I really credit the surgeons at the University of Maryland for courageous clinical work and a brilliant scientific innovation,” Clyde W. Yancy, MD, MSc, Northwestern University, Chicago, said in an interview. “But it’s always in the implementation that we have to hold our breath.” Heart xenotransplantation is an old idea that “has never before been successful,” he said. And standard heart transplantation has set a high bar, with a 1-year survival of about 90% and low 1-year risk for rejection. Whether the new procedure can meet that standard is unknown, as is its potential for complications, such as chronic rejection or cancers due to long-term immunosuppression. Those are “major questions requiring more time and careful follow-up.”

‘Still a nascent technology’

“This is an exciting and courageous step forward in heart transplantation, and kudos to the team at the University of Maryland,” said Mandeep R. Mehra, MD, Brigham and Woman’s Hospital, Boston. But “there are many challenges here.”

University of Maryland Medical Center

The procedure’s 10 gene modifications were reportedly aimed at preventing hyperacute rejection of the heart and its excessive growth after transplantation, and making the organ less immunogenic, Dr. Mehra said in an interview. But even if those goals are met, could the same changes potentially impede the heart’s adaptation to human physiology, such as during ambulation or stress?

That kind of adaptation may become important. For example, Dr. Mehra observed, normally a pig heart “provides flow in a four-footed configuration, and pig temperature is inherently higher than humans by several degrees, so it will be functioning in a relatively hypothermic environment.”

Transplantation remains the gold standard for patients with advanced heart failure despite modern medical and device therapy, Dr. Allen agreed. But “if we can raise pig hearts that provide the organ, and it can be implanted with a surgery that’s been done for 50 years, and rejection can be managed with gene editing and tailored immunosuppression, then it’s not hard to think about this very rapidly replacing a lot of what we do in the advanced heart failure and transplantation world.”

Certainly, it would be a major advance if the gene editing technique successfully improves the heart’s immunologic compatibility, Dr. Yancy noted. But do we have enough genomic knowledge to select gene deletions and insertions in the safest way for a successful outcome? “We have to appreciate that this is still a nascent technology, and we should be careful that there might be consequences that we haven’t anticipated.”

For example, he said, the xenotransplantation and gene-modifying techniques should be explored in a range of patients, including older and younger people, women and men, and people of different ethnicities and races.

“There may be some differences based on ancestry, based on gender, based on aging, that will influence the way in which these engineered donor hearts are experienced clinically,” Dr. Yancy said.

The xenotransplantation technique’s potential impact on health equity should also be considered, as it “almost assuredly will be a very expensive technology that will be utilized in a very select population,” he noted. “We need to have a really wide lens to think about all of the potential ramifications.”
 

‘This field needs to evolve’

Dr. Mehra also flagged the procedure’s potential cost should it become mainstream. Perhaps that would promote dialogue on how to primarily use it “after legitimately exhausting all available options, such as total artificial heart support.”

It might also teach the field to take greater advantage of the many donated hearts discarded as suboptimal. “The general usage rate for offered organs is around a third,” despite opportunities to expand use of those that are “less than perfect,” Dr. Mehra said. “I think that the field will grow with the community focusing on reduced discards of current available heart organs, and not necessarily grow because of the availability of ‘xeno-organs.’ ”

“This field needs to evolve because we’re actively transplanting patients today. But in my mind, the real future is to have such a sufficient understanding of the biology of left ventricular dysfunction that transplantation is a rare event,” Dr. Yancy proposed.

“I’m not certain that heart transplantation per se is the endgame. I think the avoidance of transplantation is the real endgame,” he said. “This may be controversial, but my vision of the future is not one where we have a supply of animals that we can use for transplantation. My vision of the future is that heart transplantation becomes obsolete.”

A version of this article first appeared on Medscape.com.

A genetically modified pig heart has been successfully transplanted into a 57-year-old man who had no other treatment options but is “doing well” 3 days after the procedure, officials at the University of Maryland Medical Center (UMMC), Baltimore, announced Jan. 10.

“This organ transplant demonstrated for the first time that a genetically modified animal heart can function like a human heart without immediate rejection by the body,” they said.

Three genes associated with antibody-mediated rejection had been knocked out in the pig supplying the transplanted heart, and six human genes associated with immune acceptance of the organ had been inserted into the pig’s genome, notes a UMMC press release.

University of Maryland Medical Center

A version of this article first appeared on Medscape.com.

A genetically modified pig heart has been successfully transplanted into a 57-year-old man who had no other treatment options but is “doing well” 3 days after the procedure, officials at the University of Maryland Medical Center (UMMC), Baltimore, announced Jan. 10.

“This organ transplant demonstrated for the first time that a genetically modified animal heart can function like a human heart without immediate rejection by the body,” they said.

Three genes associated with antibody-mediated rejection had been knocked out in the pig supplying the transplanted heart, and six human genes associated with immune acceptance of the organ had been inserted into the pig’s genome, notes a UMMC press release.

University of Maryland Medical Center

A version of this article first appeared on Medscape.com.

A genetically modified pig heart has been successfully transplanted into a 57-year-old man who had no other treatment options but is “doing well” 3 days after the procedure, officials at the University of Maryland Medical Center (UMMC), Baltimore, announced Jan. 10.

“This organ transplant demonstrated for the first time that a genetically modified animal heart can function like a human heart without immediate rejection by the body,” they said.

Three genes associated with antibody-mediated rejection had been knocked out in the pig supplying the transplanted heart, and six human genes associated with immune acceptance of the organ had been inserted into the pig’s genome, notes a UMMC press release.

University of Maryland Medical Center

A version of this article first appeared on Medscape.com.

In 2014, when the Food and Drug Administration found serious problems with a life-sustaining heart pump, its warning letter to the manufacturer threatened to notify other federal health agencies about the inspection’s findings.

But for years, no such alert ever went out. Instead, the agency added the warning letter to an online database alongside thousands of others, following its typical procedures, an FDA spokesperson said.

Agencies such as the Centers for Medicare & Medicaid Services and the U.S. Department of Veterans Affairs went on paying to implant the HeartWare Ventricular Assist Device, or HVAD, in new patients even though federal inspectors had found problems with the device linked to patient deaths and injuries.

Taxpayer dollars continued to flow to the original device maker, HeartWare, and then to the company that acquired it in 2016, Medtronic, for 7 years while the issues raised in the warning letter remained unresolved.

If crucial safety information in FDA warning letters doesn’t make it to other arms of the government responsible for deciding which medical devices to pay for, experts said patients are the ones put at risk.

“It’s clearly a breakdown of communication,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who researches medical device safety and regulation. “It’s not just the money, obviously. It’s people’s lives.”

The FDA acknowledged that it doesn’t directly notify other agencies when it issues warning letters, pointing instead to its online database, which is accessible to both government officials and the public. “The FDA’s decisions are intended to be patient-centric with the health and safety of device users as our highest priority,” the agency spokesperson said in an email.

The HeartWare letter was removed from the public database about 2 years ago, even though the problems remained unresolved and patients were still receiving implants. The database clears out letters that are more than 5 years old.

CMS, which oversees the Medicare and Medicaid programs, would not say why it continued paying for a device that didn’t meet government standards. It directed questions about the HeartWare warning letter to the FDA. “CMS does not have oversight of the manufacturing and related safety assessments of a medical device manufacturer,” a spokesperson said in an email.

The spokesperson noted that CMS requires heart pump patients to have specialized medical teams managing their care, which should monitor FDA communications regarding safety of devices.

CMS doesn’t track data on devices by manufacturer, so it’s essentially impossible to calculate its total spending on HVADs. One 2018 medical journal study found that Medicare and Medicaid paid for more than half the cost of all heart pump implants from 2009 to 2014. If that rate of spending continued, CMS may have spent more than $400 million on implanting HVADs since 2014.

A spokesperson for the VA said his agency was never notified about the HeartWare warning letter. The VA paid HeartWare and Medtronic more than $3 million after the FDA issued the letter in 2014. It offered this explanation for why: “It’s important to note that FDA Warning Letters are notifications issued to manufacturers found to be in significant violation of federal regulations. They are not product recalls.”

In the case of the HVAD, the FDA’s failure to make sure its warning reached beyond the manufacturer may have had life-and-death consequences.

In August, ProPublica reported that federal inspectors continued finding problems at the HVAD’s manufacturing plant for years. Meanwhile, the FDA received thousands of reports of suspicious deaths and injuries and more than a dozen high-risk safety alerts from the manufacturer.

The documents detailed one horrifying device failure after another. A father of four died after his device suddenly failed and his teenage daughter couldn’t resuscitate him. Another patient’s heart tissue was charred after a pump short-circuited and overheated. A teenager died after vomiting blood as his mother struggled to restart a defective pump.

In June, Medtronic ended sales and implants of the device, citing new data that showed patients with HVADs had a higher rate of deaths and strokes than those with a competing heart pump.

Medtronic declined to comment for this story. It has previously said it believed that after the 2014 warning letter the benefits of the HVAD still outweighed the risks for patients with severe heart failure.

Experts said the lack of communication between federal agencies when serious device problems are found is baffling but not surprising. It fits a broader trend of device regulators focusing more on evaluating new products than monitoring the ones already on the market.

“The priority is to get more medical devices out there, paid for and getting used,” said Dr. Joseph Ross, a professor of medicine and public health at Yale University who studies medical device regulation.

Other U.S. health care regulators move more forcefully when providers and suppliers don’t meet the government’s minimum safety requirements for an extended period, putting patients at risk.

Take hospitals. When inspectors find a facility is not meeting safety standards, CMS can issue an immediate jeopardy citation and, if problems aren’t fixed, move to withhold federal payments, which make up substantial portions of most hospitals’ revenues. In the rare cases when hospitals don’t take sufficient action, CMS follows through and revokes funding.

Redberg, the UCSF cardiologist, said the lack of similar action for medical devices offers a clear “opportunity for improvement.” At minimum, the FDA could establish processes to directly inform other agencies when it issues warning letters and finds serious problems with devices being sold in the United States.

“If the agency’s mission is to protect public health, they would want to do these things and move quickly,” she said.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

In 2014, when the Food and Drug Administration found serious problems with a life-sustaining heart pump, its warning letter to the manufacturer threatened to notify other federal health agencies about the inspection’s findings.

But for years, no such alert ever went out. Instead, the agency added the warning letter to an online database alongside thousands of others, following its typical procedures, an FDA spokesperson said.

Agencies such as the Centers for Medicare & Medicaid Services and the U.S. Department of Veterans Affairs went on paying to implant the HeartWare Ventricular Assist Device, or HVAD, in new patients even though federal inspectors had found problems with the device linked to patient deaths and injuries.

Taxpayer dollars continued to flow to the original device maker, HeartWare, and then to the company that acquired it in 2016, Medtronic, for 7 years while the issues raised in the warning letter remained unresolved.

If crucial safety information in FDA warning letters doesn’t make it to other arms of the government responsible for deciding which medical devices to pay for, experts said patients are the ones put at risk.

“It’s clearly a breakdown of communication,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who researches medical device safety and regulation. “It’s not just the money, obviously. It’s people’s lives.”

The FDA acknowledged that it doesn’t directly notify other agencies when it issues warning letters, pointing instead to its online database, which is accessible to both government officials and the public. “The FDA’s decisions are intended to be patient-centric with the health and safety of device users as our highest priority,” the agency spokesperson said in an email.

The HeartWare letter was removed from the public database about 2 years ago, even though the problems remained unresolved and patients were still receiving implants. The database clears out letters that are more than 5 years old.

CMS, which oversees the Medicare and Medicaid programs, would not say why it continued paying for a device that didn’t meet government standards. It directed questions about the HeartWare warning letter to the FDA. “CMS does not have oversight of the manufacturing and related safety assessments of a medical device manufacturer,” a spokesperson said in an email.

The spokesperson noted that CMS requires heart pump patients to have specialized medical teams managing their care, which should monitor FDA communications regarding safety of devices.

CMS doesn’t track data on devices by manufacturer, so it’s essentially impossible to calculate its total spending on HVADs. One 2018 medical journal study found that Medicare and Medicaid paid for more than half the cost of all heart pump implants from 2009 to 2014. If that rate of spending continued, CMS may have spent more than $400 million on implanting HVADs since 2014.

A spokesperson for the VA said his agency was never notified about the HeartWare warning letter. The VA paid HeartWare and Medtronic more than $3 million after the FDA issued the letter in 2014. It offered this explanation for why: “It’s important to note that FDA Warning Letters are notifications issued to manufacturers found to be in significant violation of federal regulations. They are not product recalls.”

In the case of the HVAD, the FDA’s failure to make sure its warning reached beyond the manufacturer may have had life-and-death consequences.

In August, ProPublica reported that federal inspectors continued finding problems at the HVAD’s manufacturing plant for years. Meanwhile, the FDA received thousands of reports of suspicious deaths and injuries and more than a dozen high-risk safety alerts from the manufacturer.

The documents detailed one horrifying device failure after another. A father of four died after his device suddenly failed and his teenage daughter couldn’t resuscitate him. Another patient’s heart tissue was charred after a pump short-circuited and overheated. A teenager died after vomiting blood as his mother struggled to restart a defective pump.

In June, Medtronic ended sales and implants of the device, citing new data that showed patients with HVADs had a higher rate of deaths and strokes than those with a competing heart pump.

Medtronic declined to comment for this story. It has previously said it believed that after the 2014 warning letter the benefits of the HVAD still outweighed the risks for patients with severe heart failure.

Experts said the lack of communication between federal agencies when serious device problems are found is baffling but not surprising. It fits a broader trend of device regulators focusing more on evaluating new products than monitoring the ones already on the market.

“The priority is to get more medical devices out there, paid for and getting used,” said Dr. Joseph Ross, a professor of medicine and public health at Yale University who studies medical device regulation.

Other U.S. health care regulators move more forcefully when providers and suppliers don’t meet the government’s minimum safety requirements for an extended period, putting patients at risk.

Take hospitals. When inspectors find a facility is not meeting safety standards, CMS can issue an immediate jeopardy citation and, if problems aren’t fixed, move to withhold federal payments, which make up substantial portions of most hospitals’ revenues. In the rare cases when hospitals don’t take sufficient action, CMS follows through and revokes funding.

Redberg, the UCSF cardiologist, said the lack of similar action for medical devices offers a clear “opportunity for improvement.” At minimum, the FDA could establish processes to directly inform other agencies when it issues warning letters and finds serious problems with devices being sold in the United States.

“If the agency’s mission is to protect public health, they would want to do these things and move quickly,” she said.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

In 2014, when the Food and Drug Administration found serious problems with a life-sustaining heart pump, its warning letter to the manufacturer threatened to notify other federal health agencies about the inspection’s findings.

But for years, no such alert ever went out. Instead, the agency added the warning letter to an online database alongside thousands of others, following its typical procedures, an FDA spokesperson said.

Agencies such as the Centers for Medicare & Medicaid Services and the U.S. Department of Veterans Affairs went on paying to implant the HeartWare Ventricular Assist Device, or HVAD, in new patients even though federal inspectors had found problems with the device linked to patient deaths and injuries.

Taxpayer dollars continued to flow to the original device maker, HeartWare, and then to the company that acquired it in 2016, Medtronic, for 7 years while the issues raised in the warning letter remained unresolved.

If crucial safety information in FDA warning letters doesn’t make it to other arms of the government responsible for deciding which medical devices to pay for, experts said patients are the ones put at risk.

“It’s clearly a breakdown of communication,” said Dr. Rita Redberg, a cardiologist at the University of California, San Francisco, who researches medical device safety and regulation. “It’s not just the money, obviously. It’s people’s lives.”

The FDA acknowledged that it doesn’t directly notify other agencies when it issues warning letters, pointing instead to its online database, which is accessible to both government officials and the public. “The FDA’s decisions are intended to be patient-centric with the health and safety of device users as our highest priority,” the agency spokesperson said in an email.

The HeartWare letter was removed from the public database about 2 years ago, even though the problems remained unresolved and patients were still receiving implants. The database clears out letters that are more than 5 years old.

CMS, which oversees the Medicare and Medicaid programs, would not say why it continued paying for a device that didn’t meet government standards. It directed questions about the HeartWare warning letter to the FDA. “CMS does not have oversight of the manufacturing and related safety assessments of a medical device manufacturer,” a spokesperson said in an email.

The spokesperson noted that CMS requires heart pump patients to have specialized medical teams managing their care, which should monitor FDA communications regarding safety of devices.

CMS doesn’t track data on devices by manufacturer, so it’s essentially impossible to calculate its total spending on HVADs. One 2018 medical journal study found that Medicare and Medicaid paid for more than half the cost of all heart pump implants from 2009 to 2014. If that rate of spending continued, CMS may have spent more than $400 million on implanting HVADs since 2014.

A spokesperson for the VA said his agency was never notified about the HeartWare warning letter. The VA paid HeartWare and Medtronic more than $3 million after the FDA issued the letter in 2014. It offered this explanation for why: “It’s important to note that FDA Warning Letters are notifications issued to manufacturers found to be in significant violation of federal regulations. They are not product recalls.”

In the case of the HVAD, the FDA’s failure to make sure its warning reached beyond the manufacturer may have had life-and-death consequences.

In August, ProPublica reported that federal inspectors continued finding problems at the HVAD’s manufacturing plant for years. Meanwhile, the FDA received thousands of reports of suspicious deaths and injuries and more than a dozen high-risk safety alerts from the manufacturer.

The documents detailed one horrifying device failure after another. A father of four died after his device suddenly failed and his teenage daughter couldn’t resuscitate him. Another patient’s heart tissue was charred after a pump short-circuited and overheated. A teenager died after vomiting blood as his mother struggled to restart a defective pump.

In June, Medtronic ended sales and implants of the device, citing new data that showed patients with HVADs had a higher rate of deaths and strokes than those with a competing heart pump.

Medtronic declined to comment for this story. It has previously said it believed that after the 2014 warning letter the benefits of the HVAD still outweighed the risks for patients with severe heart failure.

Experts said the lack of communication between federal agencies when serious device problems are found is baffling but not surprising. It fits a broader trend of device regulators focusing more on evaluating new products than monitoring the ones already on the market.

“The priority is to get more medical devices out there, paid for and getting used,” said Dr. Joseph Ross, a professor of medicine and public health at Yale University who studies medical device regulation.

Other U.S. health care regulators move more forcefully when providers and suppliers don’t meet the government’s minimum safety requirements for an extended period, putting patients at risk.

Take hospitals. When inspectors find a facility is not meeting safety standards, CMS can issue an immediate jeopardy citation and, if problems aren’t fixed, move to withhold federal payments, which make up substantial portions of most hospitals’ revenues. In the rare cases when hospitals don’t take sufficient action, CMS follows through and revokes funding.

Redberg, the UCSF cardiologist, said the lack of similar action for medical devices offers a clear “opportunity for improvement.” At minimum, the FDA could establish processes to directly inform other agencies when it issues warning letters and finds serious problems with devices being sold in the United States.

“If the agency’s mission is to protect public health, they would want to do these things and move quickly,” she said.

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

The damage to the heart caused by a myocardial infarction is not just a result of ischemia caused by the blocked artery but is also brought about by bleeding in the myocardium after the artery has been opened, a new study suggests.

This observation is leading to new approaches to limiting infarct size and treating MI.

“In MI treatment, we have always focused on opening up the artery as quickly as possible to limit the myocardial damage caused by ischemia,” the study’s senior author, Rohan Dharmakumar, PhD, Indiana University, Indianapolis, told this news organization.

“We are pursuing a completely new approach focusing on limiting the damage after revascularization,” he said. “We are totally rethinking what a myocardial infarction is – what causes the injury and the time course of the injury – our results suggest that it’s not just ischemic damage and a lot of the harm is caused by hemorrhage after reperfusion.”

It has been known for many years that hemorrhage is often seen in the myocardium in large MIs, but it has not been established before now whether it contributes to the injury or not, Dr. Dharmakumar explained.

“This study was done to look at that – and we found that the hemorrhage drives a second layer of injury on top of the ischemia.”

Dr. Dharmakumar said this hemorrhage is part of the phenomenon known as reperfusion injury. “This has been known to exist for many years, but we haven’t fully understood all the factors contributing to it. Our results suggest that hemorrhage is a major component of reperfusion injury – probably the dominant factor,” he said.  

The researchers are now working on therapeutic approaches to try to prevent this hemorrhage and/or to minimize its effect.

“We are studying how hemorrhage drives damage and how to block these biological processes,” Dr. Dharmakumar said. “Our studies suggest that hemorrhage could account for up to half of the damage caused by a myocardial infarction. If we can limit that, we should be able to reduce the size of the infarct and this should translate into better long-term outcomes.

“I’m very excited about these results,” he added. “We are already seeing a remarkable improvement in animal models with some of the potential therapeutic approaches we are working on.”

The current study is published in the January 2022 issue of the Journal of the American College of Cardiology (JACC).

The authors explain that it is now recognized that reperfusion injury can contribute to increasing infarct size, which they refer to as “infarct surge.” Previous studies have also shown that reperfusion injury can contribute to as much as 50% of the final infarct size, but the factors contributing to the observed variability are not known, and previous attempts to limit infarct surge from reperfusion injury have failed.

They noted that after reperfusion, microvessels can remain obstructed, resulting in intramyocardial hemorrhage. They conducted the current study to investigate whether such hemorrhage causes expansion of the infarct.

They studied 70 patients with ST-segment elevation MI who were categorized with cardiovascular MRI to have intramyocardial hemorrhage or not following primary PCI, and for whom serial cardiac troponin measures were used to assess infarct size.

Results showed that while troponin levels were not different before reperfusion, patients with intramyocardial hemorrhage had significantly higher cardiac troponin levels after reperfusion and these levels peaked earlier than in patients without hemorrhage.

In animal models, those with intramyocardial hemorrhage had a more rapid expansion of myocardial necrosis than did those without hemorrhage, and within 72 hours of reperfusion, a fourfold greater loss in salvageable myocardium was evident in hemorrhagic MIs.

“We have shown that damage to the heart continues after revascularization as measured by rapidly increasing troponin levels in the hearts that have had a hemorrhage,” Dr. Dharmakumar said.

“Hemorrhage in the myocardium was associated with larger infarctions, and in infarcts causing the same area of myocardium to be at risk, those with hemorrhage after revascularization lost a lot more of the salvageable myocardium than those without hemorrhage,” he added.

Dr. Dharmakumar estimates that such hemorrhage occurs in about half of MIs after revascularization, with risk factors including male gender, anterior wall MIs, and smoking.

He pointed out that previous attempts to treat or prevent reperfusion injury have not been successful, probably because they have not been addressing the key mechanism. “We have not been looking at hemorrhage in this regard until now. This is because it is only recently that we have had the tools to be able to identify hemorrhage in the heart with the use of cardiac MRI.” 
 

Final frontier

In an accompanying editorial, Colin Berry, MBChB, University of Glasgow, and Borja Ibáñez, MD, Jiménez Díaz Foundation University Hospital, Madrid, said they applaud the investigators for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.

But they pointed out that it is difficult to completely dissect the impact of hemorrhage versus MI size on adverse remodeling, noting that it might be the case that more severe ischemia/reperfusion events are associated with large MI sizes and higher degree of hemorrhage.

However, they concluded that: “Intramyocardial hemorrhage represents the final frontier for preventing heart failure post-MI. It is readily detected using CMR, and clinical research of novel therapeutic approaches merits prioritization.”

This work was supported by grants from National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Dharmakumar and coauthor Robert Finney, PhD, have ownership interest in Cardiotheranostics. Dr. Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health.

A version of this article first appeared on Medscape.com.

The damage to the heart caused by a myocardial infarction is not just a result of ischemia caused by the blocked artery but is also brought about by bleeding in the myocardium after the artery has been opened, a new study suggests.

This observation is leading to new approaches to limiting infarct size and treating MI.

“In MI treatment, we have always focused on opening up the artery as quickly as possible to limit the myocardial damage caused by ischemia,” the study’s senior author, Rohan Dharmakumar, PhD, Indiana University, Indianapolis, told this news organization.

“We are pursuing a completely new approach focusing on limiting the damage after revascularization,” he said. “We are totally rethinking what a myocardial infarction is – what causes the injury and the time course of the injury – our results suggest that it’s not just ischemic damage and a lot of the harm is caused by hemorrhage after reperfusion.”

It has been known for many years that hemorrhage is often seen in the myocardium in large MIs, but it has not been established before now whether it contributes to the injury or not, Dr. Dharmakumar explained.

“This study was done to look at that – and we found that the hemorrhage drives a second layer of injury on top of the ischemia.”

Dr. Dharmakumar said this hemorrhage is part of the phenomenon known as reperfusion injury. “This has been known to exist for many years, but we haven’t fully understood all the factors contributing to it. Our results suggest that hemorrhage is a major component of reperfusion injury – probably the dominant factor,” he said.  

The researchers are now working on therapeutic approaches to try to prevent this hemorrhage and/or to minimize its effect.

“We are studying how hemorrhage drives damage and how to block these biological processes,” Dr. Dharmakumar said. “Our studies suggest that hemorrhage could account for up to half of the damage caused by a myocardial infarction. If we can limit that, we should be able to reduce the size of the infarct and this should translate into better long-term outcomes.

“I’m very excited about these results,” he added. “We are already seeing a remarkable improvement in animal models with some of the potential therapeutic approaches we are working on.”

The current study is published in the January 2022 issue of the Journal of the American College of Cardiology (JACC).

The authors explain that it is now recognized that reperfusion injury can contribute to increasing infarct size, which they refer to as “infarct surge.” Previous studies have also shown that reperfusion injury can contribute to as much as 50% of the final infarct size, but the factors contributing to the observed variability are not known, and previous attempts to limit infarct surge from reperfusion injury have failed.

They noted that after reperfusion, microvessels can remain obstructed, resulting in intramyocardial hemorrhage. They conducted the current study to investigate whether such hemorrhage causes expansion of the infarct.

They studied 70 patients with ST-segment elevation MI who were categorized with cardiovascular MRI to have intramyocardial hemorrhage or not following primary PCI, and for whom serial cardiac troponin measures were used to assess infarct size.

Results showed that while troponin levels were not different before reperfusion, patients with intramyocardial hemorrhage had significantly higher cardiac troponin levels after reperfusion and these levels peaked earlier than in patients without hemorrhage.

In animal models, those with intramyocardial hemorrhage had a more rapid expansion of myocardial necrosis than did those without hemorrhage, and within 72 hours of reperfusion, a fourfold greater loss in salvageable myocardium was evident in hemorrhagic MIs.

“We have shown that damage to the heart continues after revascularization as measured by rapidly increasing troponin levels in the hearts that have had a hemorrhage,” Dr. Dharmakumar said.

“Hemorrhage in the myocardium was associated with larger infarctions, and in infarcts causing the same area of myocardium to be at risk, those with hemorrhage after revascularization lost a lot more of the salvageable myocardium than those without hemorrhage,” he added.

Dr. Dharmakumar estimates that such hemorrhage occurs in about half of MIs after revascularization, with risk factors including male gender, anterior wall MIs, and smoking.

He pointed out that previous attempts to treat or prevent reperfusion injury have not been successful, probably because they have not been addressing the key mechanism. “We have not been looking at hemorrhage in this regard until now. This is because it is only recently that we have had the tools to be able to identify hemorrhage in the heart with the use of cardiac MRI.” 
 

Final frontier

In an accompanying editorial, Colin Berry, MBChB, University of Glasgow, and Borja Ibáñez, MD, Jiménez Díaz Foundation University Hospital, Madrid, said they applaud the investigators for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.

But they pointed out that it is difficult to completely dissect the impact of hemorrhage versus MI size on adverse remodeling, noting that it might be the case that more severe ischemia/reperfusion events are associated with large MI sizes and higher degree of hemorrhage.

However, they concluded that: “Intramyocardial hemorrhage represents the final frontier for preventing heart failure post-MI. It is readily detected using CMR, and clinical research of novel therapeutic approaches merits prioritization.”

This work was supported by grants from National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Dharmakumar and coauthor Robert Finney, PhD, have ownership interest in Cardiotheranostics. Dr. Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health.

A version of this article first appeared on Medscape.com.

The damage to the heart caused by a myocardial infarction is not just a result of ischemia caused by the blocked artery but is also brought about by bleeding in the myocardium after the artery has been opened, a new study suggests.

This observation is leading to new approaches to limiting infarct size and treating MI.

“In MI treatment, we have always focused on opening up the artery as quickly as possible to limit the myocardial damage caused by ischemia,” the study’s senior author, Rohan Dharmakumar, PhD, Indiana University, Indianapolis, told this news organization.

“We are pursuing a completely new approach focusing on limiting the damage after revascularization,” he said. “We are totally rethinking what a myocardial infarction is – what causes the injury and the time course of the injury – our results suggest that it’s not just ischemic damage and a lot of the harm is caused by hemorrhage after reperfusion.”

It has been known for many years that hemorrhage is often seen in the myocardium in large MIs, but it has not been established before now whether it contributes to the injury or not, Dr. Dharmakumar explained.

“This study was done to look at that – and we found that the hemorrhage drives a second layer of injury on top of the ischemia.”

Dr. Dharmakumar said this hemorrhage is part of the phenomenon known as reperfusion injury. “This has been known to exist for many years, but we haven’t fully understood all the factors contributing to it. Our results suggest that hemorrhage is a major component of reperfusion injury – probably the dominant factor,” he said.  

The researchers are now working on therapeutic approaches to try to prevent this hemorrhage and/or to minimize its effect.

“We are studying how hemorrhage drives damage and how to block these biological processes,” Dr. Dharmakumar said. “Our studies suggest that hemorrhage could account for up to half of the damage caused by a myocardial infarction. If we can limit that, we should be able to reduce the size of the infarct and this should translate into better long-term outcomes.

“I’m very excited about these results,” he added. “We are already seeing a remarkable improvement in animal models with some of the potential therapeutic approaches we are working on.”

The current study is published in the January 2022 issue of the Journal of the American College of Cardiology (JACC).

The authors explain that it is now recognized that reperfusion injury can contribute to increasing infarct size, which they refer to as “infarct surge.” Previous studies have also shown that reperfusion injury can contribute to as much as 50% of the final infarct size, but the factors contributing to the observed variability are not known, and previous attempts to limit infarct surge from reperfusion injury have failed.

They noted that after reperfusion, microvessels can remain obstructed, resulting in intramyocardial hemorrhage. They conducted the current study to investigate whether such hemorrhage causes expansion of the infarct.

They studied 70 patients with ST-segment elevation MI who were categorized with cardiovascular MRI to have intramyocardial hemorrhage or not following primary PCI, and for whom serial cardiac troponin measures were used to assess infarct size.

Results showed that while troponin levels were not different before reperfusion, patients with intramyocardial hemorrhage had significantly higher cardiac troponin levels after reperfusion and these levels peaked earlier than in patients without hemorrhage.

In animal models, those with intramyocardial hemorrhage had a more rapid expansion of myocardial necrosis than did those without hemorrhage, and within 72 hours of reperfusion, a fourfold greater loss in salvageable myocardium was evident in hemorrhagic MIs.

“We have shown that damage to the heart continues after revascularization as measured by rapidly increasing troponin levels in the hearts that have had a hemorrhage,” Dr. Dharmakumar said.

“Hemorrhage in the myocardium was associated with larger infarctions, and in infarcts causing the same area of myocardium to be at risk, those with hemorrhage after revascularization lost a lot more of the salvageable myocardium than those without hemorrhage,” he added.

Dr. Dharmakumar estimates that such hemorrhage occurs in about half of MIs after revascularization, with risk factors including male gender, anterior wall MIs, and smoking.

He pointed out that previous attempts to treat or prevent reperfusion injury have not been successful, probably because they have not been addressing the key mechanism. “We have not been looking at hemorrhage in this regard until now. This is because it is only recently that we have had the tools to be able to identify hemorrhage in the heart with the use of cardiac MRI.” 
 

Final frontier

In an accompanying editorial, Colin Berry, MBChB, University of Glasgow, and Borja Ibáñez, MD, Jiménez Díaz Foundation University Hospital, Madrid, said they applaud the investigators for providing new, mechanistic insights into a difficult clinical problem that has an unmet therapeutic need.

But they pointed out that it is difficult to completely dissect the impact of hemorrhage versus MI size on adverse remodeling, noting that it might be the case that more severe ischemia/reperfusion events are associated with large MI sizes and higher degree of hemorrhage.

However, they concluded that: “Intramyocardial hemorrhage represents the final frontier for preventing heart failure post-MI. It is readily detected using CMR, and clinical research of novel therapeutic approaches merits prioritization.”

This work was supported by grants from National Institutes of Health/National Heart, Lung, and Blood Institute. Dr. Dharmakumar and coauthor Robert Finney, PhD, have ownership interest in Cardiotheranostics. Dr. Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health.

A version of this article first appeared on Medscape.com.