Interventional Cardiology & Surgery

Prediction models that incorporate more than just treatment status could rank order heart transplant candidates by urgency more effectively than the current system, a modeling study suggests.

Since 2018, the U.S. heart transplant allocation system has ranked heart candidates according to six treatment-based “statuses” (up from three used previously), ignoring many objective patient characteristics, the authors write.

Their study showed no significant difference in survival between statuses four and six, and status five had lower survival than status four.

“We expected multivariable prediction models to outperform the six-status system when it comes to rank ordering patients by how likely they are to die on the wait list (medical urgency),” William F. Parker, MD, MS, PhD, of the University of Chicago, told this news organization.

“However, we were surprised to see that the statuses were out of order,” he said. “Status five patients are more urgent than status three or status four patients,” mainly because most are in renal failure and listed for multiorgan transplantation with a kidney.

Objective physiologic measurements, such as glomerular filtration rate (GFR), had high variable importance, offering a minimally invasive measurement with predictive power in assessing medical urgency. Therefore, including GFR and other variables such as extracorporeal membrane oxygenation (ECMO) could improve the accuracy of the allocation system in identifying the most medically urgent candidates, Dr. Parker and colleagues suggest.

The study was published online in JACC: Heart Failure.
 

‘Moderate ability’ to rank order

The investigators assessed the effectiveness of the standard six-status ranking system and several novel prediction models in identifying the most urgent heart transplant candidates. The primary outcome was death before receipt of a heart transplant.

The final data set contained 32,294 candidates (mean age, 53 years; 74%, men); 27,200 made up the prepolicy training set and 5,094 were included in the postpolicy test set.

The team evaluated the accuracy of the six-status system using Harrell’s C-index and log-rank tests of Kaplan-Meier estimated survival by status for candidates listed after the policy change (November 2018 to March 2020) in the Scientific Registry of Transplant Recipients data set.

They then developed Cox proportional hazards models and random survival forest models using prepolicy data (2010-2017). Predictor variables included age, diagnosis, laboratory measurements, hemodynamics, and supportive treatment at the time of listing.

They found that the six-status ranking at listing has had “moderate ability” to rank order candidates.

As Dr. Parker indicated, statuses four and six had no significant difference in survival, and status five had lower survival than status four.

The investigators’ multivariable prediction models derived with prepolicy data ranked candidates correctly more often than the six-status rankings. Objective physiologic measurements, such as GFR and ECMO, were identified as having significant importance with regard to ranking by urgency.

“The novel prediction models we developed … could be implemented by the Organ Procurement and Transplantation Network (OPTN) as allocation policy and would be better than the status quo,” Dr. Parker said. “However, I think we could do even better using the newer data collected after 2018.” 
 

Modifications underway

The OPTN Heart Transplantation Committee is currently working on developing a new framework for allocating deceased donor hearts called Continuous Distribution.

“The six-tiered system works well, and it better stratifies the most medically urgent candidates than the previous allocation framework,” the leadership of the United Network for Organ Sharing Heart Transplantation Committee, including Chair Richard C. Daly, MD, Mayo Clinic; Vice-Chair Jondavid Menteer, MD, University of Southern California, Los Angeles; and former Chair Shelley Hall, MD, Baylor University Medical Center, told this news organization.

“That said, it is always appropriate to review and adjust variables that affect the medical urgency attribute for heart allocation.”

The new framework will change how patients are prioritized, they said. “Continuous distribution will consider all patient factors, including medical urgency, together to determine the order of an organ offer, and no single factor will decide an organ match.

“The goal is to increase fairness by moving to a points-based allocation framework that allows candidates to be compared using a single score composed of multiple factors.

“Furthermore,” they added, “continuous distribution provides a framework that will allow modifications of the criteria defining medical urgency (and other attributes of allocation) to a finer degree than the current policy. … Once continuous distribution is in place and the OPTN has policy monitoring data, the committee may consider and model different ways of defining medical urgency.”

Kiran K. Khush, MD, of Stanford (Calif.) University School of Medicine, coauthor of a related commentary, elaborated. “The composite allocation score (CAS) will consist of a ‘points-based system,’ in which candidates will be assigned points based on (1) medical urgency, (2) anticipated posttransplant survival, (3) candidate biology (eg., special characteristics that may result in higher prioritization, such as blood type O and allosensitization), (4) access (eg., prior living donor, pediatric patient), and (5) placement efficacy (travel, proximity).”

Candidates will be assigned points based on these categories, and will be rank ordered for each donor offer.

Dr. Khush and colleagues propose that a multivariable model – such as the ones described in the study – would be the best way to assign points for medical urgency.

“This system will be more equitable than the current system,” Dr. Khush said, “because it will better prioritize the sickest candidates while improving access for patients who are currently at a disadvantage [for example, blood O, highly sensitized patients], and will also remove artificial geographic boundaries [for example, the current 500-mile rule for heart allocation].”
 

Going further

Jesse D. Schold, PhD, of the University of Colorado at Denver, Aurora, raises concerns about other aspects of the heart allocation system in another related commentary.

“One big issue with our data in transplantation … is that, while it is very comprehensive for capturing transplant candidates and recipients, there is no data collection for patients and processes of care for patients prior to wait list placement,” he told this news organization. This phase of care is subject to wide variation in practice, he said, “and is likely as important as any to patients – the ability to be referred, evaluated, and placed on a waiting list.”

Report cards that measure quality of care after wait list placement ignore key phases prior to wait list placement, he said. “This may have the unintended consequences of limiting access to care and to the waiting list for patients perceived to be at higher risk, or the use of higher-risk donors, despite their potential survival advantage.

“In contrast,” he said, “quality report cards that incentivize treatment for all patients who may benefit would likely have a greater beneficial impact on patients with end-organ disease.”

There is also significant risk of underlying differences in patient populations between centers, despite the use of multivariable models, he added. This heterogeneity “may not be reflected accurately in the report cards [which] have significant impact for regulatory review, private payer contracting, and center reputation.”

Some of these concerns may be addressed in the new OPTN Modernization Initiative, according to David Bowman, a public affairs specialist at the Health Resources and Services Administration. One of the goals of the initiative “is to ensure that the OPTN Board of Directors is high functioning, has greater independence, and represents the diversity of communities served by the OPTN,” he told this news organization. “Strengthened governance will lead to effective policy development and implementation, and enhanced transparency and accountability of the process.”

Addressing another concern about the system, Savitri Fedson, MD, of the Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, wonders in a related editorial whether organ donors and recipients should know more about each other, and if so, could that reverse the ongoing downward trend in organ acceptance?

Although some organizations are in favor of sharing more information, Dr. Fedson notes that “less information may have the greater benefit.” She writes, “We might realize that the simplest approach is often the best: a fulsome thank you for the donor’s gift that is willingly given to a stranger without expectation of payment, and on the recipient side, the knowledge that an organ is of good quality.

“The transplant patient can be comforted with the understanding that the risk of disease transmission, while not zero, is low, and that their survival following acceptance of an organ is better than languishing on a waiting list.”

The study received no commercial funding. Dr. Parker, Dr. Khush, Dr. Schold, and Dr. Fedson report no relevant financial relationships.

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

Prediction models that incorporate more than just treatment status could rank order heart transplant candidates by urgency more effectively than the current system, a modeling study suggests.

Since 2018, the U.S. heart transplant allocation system has ranked heart candidates according to six treatment-based “statuses” (up from three used previously), ignoring many objective patient characteristics, the authors write.

Their study showed no significant difference in survival between statuses four and six, and status five had lower survival than status four.

“We expected multivariable prediction models to outperform the six-status system when it comes to rank ordering patients by how likely they are to die on the wait list (medical urgency),” William F. Parker, MD, MS, PhD, of the University of Chicago, told this news organization.

“However, we were surprised to see that the statuses were out of order,” he said. “Status five patients are more urgent than status three or status four patients,” mainly because most are in renal failure and listed for multiorgan transplantation with a kidney.

Objective physiologic measurements, such as glomerular filtration rate (GFR), had high variable importance, offering a minimally invasive measurement with predictive power in assessing medical urgency. Therefore, including GFR and other variables such as extracorporeal membrane oxygenation (ECMO) could improve the accuracy of the allocation system in identifying the most medically urgent candidates, Dr. Parker and colleagues suggest.

The study was published online in JACC: Heart Failure.
 

‘Moderate ability’ to rank order

The investigators assessed the effectiveness of the standard six-status ranking system and several novel prediction models in identifying the most urgent heart transplant candidates. The primary outcome was death before receipt of a heart transplant.

The final data set contained 32,294 candidates (mean age, 53 years; 74%, men); 27,200 made up the prepolicy training set and 5,094 were included in the postpolicy test set.

The team evaluated the accuracy of the six-status system using Harrell’s C-index and log-rank tests of Kaplan-Meier estimated survival by status for candidates listed after the policy change (November 2018 to March 2020) in the Scientific Registry of Transplant Recipients data set.

They then developed Cox proportional hazards models and random survival forest models using prepolicy data (2010-2017). Predictor variables included age, diagnosis, laboratory measurements, hemodynamics, and supportive treatment at the time of listing.

They found that the six-status ranking at listing has had “moderate ability” to rank order candidates.

As Dr. Parker indicated, statuses four and six had no significant difference in survival, and status five had lower survival than status four.

The investigators’ multivariable prediction models derived with prepolicy data ranked candidates correctly more often than the six-status rankings. Objective physiologic measurements, such as GFR and ECMO, were identified as having significant importance with regard to ranking by urgency.

“The novel prediction models we developed … could be implemented by the Organ Procurement and Transplantation Network (OPTN) as allocation policy and would be better than the status quo,” Dr. Parker said. “However, I think we could do even better using the newer data collected after 2018.” 
 

Modifications underway

The OPTN Heart Transplantation Committee is currently working on developing a new framework for allocating deceased donor hearts called Continuous Distribution.

“The six-tiered system works well, and it better stratifies the most medically urgent candidates than the previous allocation framework,” the leadership of the United Network for Organ Sharing Heart Transplantation Committee, including Chair Richard C. Daly, MD, Mayo Clinic; Vice-Chair Jondavid Menteer, MD, University of Southern California, Los Angeles; and former Chair Shelley Hall, MD, Baylor University Medical Center, told this news organization.

“That said, it is always appropriate to review and adjust variables that affect the medical urgency attribute for heart allocation.”

The new framework will change how patients are prioritized, they said. “Continuous distribution will consider all patient factors, including medical urgency, together to determine the order of an organ offer, and no single factor will decide an organ match.

“The goal is to increase fairness by moving to a points-based allocation framework that allows candidates to be compared using a single score composed of multiple factors.

“Furthermore,” they added, “continuous distribution provides a framework that will allow modifications of the criteria defining medical urgency (and other attributes of allocation) to a finer degree than the current policy. … Once continuous distribution is in place and the OPTN has policy monitoring data, the committee may consider and model different ways of defining medical urgency.”

Kiran K. Khush, MD, of Stanford (Calif.) University School of Medicine, coauthor of a related commentary, elaborated. “The composite allocation score (CAS) will consist of a ‘points-based system,’ in which candidates will be assigned points based on (1) medical urgency, (2) anticipated posttransplant survival, (3) candidate biology (eg., special characteristics that may result in higher prioritization, such as blood type O and allosensitization), (4) access (eg., prior living donor, pediatric patient), and (5) placement efficacy (travel, proximity).”

Candidates will be assigned points based on these categories, and will be rank ordered for each donor offer.

Dr. Khush and colleagues propose that a multivariable model – such as the ones described in the study – would be the best way to assign points for medical urgency.

“This system will be more equitable than the current system,” Dr. Khush said, “because it will better prioritize the sickest candidates while improving access for patients who are currently at a disadvantage [for example, blood O, highly sensitized patients], and will also remove artificial geographic boundaries [for example, the current 500-mile rule for heart allocation].”
 

Going further

Jesse D. Schold, PhD, of the University of Colorado at Denver, Aurora, raises concerns about other aspects of the heart allocation system in another related commentary.

“One big issue with our data in transplantation … is that, while it is very comprehensive for capturing transplant candidates and recipients, there is no data collection for patients and processes of care for patients prior to wait list placement,” he told this news organization. This phase of care is subject to wide variation in practice, he said, “and is likely as important as any to patients – the ability to be referred, evaluated, and placed on a waiting list.”

Report cards that measure quality of care after wait list placement ignore key phases prior to wait list placement, he said. “This may have the unintended consequences of limiting access to care and to the waiting list for patients perceived to be at higher risk, or the use of higher-risk donors, despite their potential survival advantage.

“In contrast,” he said, “quality report cards that incentivize treatment for all patients who may benefit would likely have a greater beneficial impact on patients with end-organ disease.”

There is also significant risk of underlying differences in patient populations between centers, despite the use of multivariable models, he added. This heterogeneity “may not be reflected accurately in the report cards [which] have significant impact for regulatory review, private payer contracting, and center reputation.”

Some of these concerns may be addressed in the new OPTN Modernization Initiative, according to David Bowman, a public affairs specialist at the Health Resources and Services Administration. One of the goals of the initiative “is to ensure that the OPTN Board of Directors is high functioning, has greater independence, and represents the diversity of communities served by the OPTN,” he told this news organization. “Strengthened governance will lead to effective policy development and implementation, and enhanced transparency and accountability of the process.”

Addressing another concern about the system, Savitri Fedson, MD, of the Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, wonders in a related editorial whether organ donors and recipients should know more about each other, and if so, could that reverse the ongoing downward trend in organ acceptance?

Although some organizations are in favor of sharing more information, Dr. Fedson notes that “less information may have the greater benefit.” She writes, “We might realize that the simplest approach is often the best: a fulsome thank you for the donor’s gift that is willingly given to a stranger without expectation of payment, and on the recipient side, the knowledge that an organ is of good quality.

“The transplant patient can be comforted with the understanding that the risk of disease transmission, while not zero, is low, and that their survival following acceptance of an organ is better than languishing on a waiting list.”

The study received no commercial funding. Dr. Parker, Dr. Khush, Dr. Schold, and Dr. Fedson report no relevant financial relationships.

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

Prediction models that incorporate more than just treatment status could rank order heart transplant candidates by urgency more effectively than the current system, a modeling study suggests.

Since 2018, the U.S. heart transplant allocation system has ranked heart candidates according to six treatment-based “statuses” (up from three used previously), ignoring many objective patient characteristics, the authors write.

Their study showed no significant difference in survival between statuses four and six, and status five had lower survival than status four.

“We expected multivariable prediction models to outperform the six-status system when it comes to rank ordering patients by how likely they are to die on the wait list (medical urgency),” William F. Parker, MD, MS, PhD, of the University of Chicago, told this news organization.

“However, we were surprised to see that the statuses were out of order,” he said. “Status five patients are more urgent than status three or status four patients,” mainly because most are in renal failure and listed for multiorgan transplantation with a kidney.

Objective physiologic measurements, such as glomerular filtration rate (GFR), had high variable importance, offering a minimally invasive measurement with predictive power in assessing medical urgency. Therefore, including GFR and other variables such as extracorporeal membrane oxygenation (ECMO) could improve the accuracy of the allocation system in identifying the most medically urgent candidates, Dr. Parker and colleagues suggest.

The study was published online in JACC: Heart Failure.
 

‘Moderate ability’ to rank order

The investigators assessed the effectiveness of the standard six-status ranking system and several novel prediction models in identifying the most urgent heart transplant candidates. The primary outcome was death before receipt of a heart transplant.

The final data set contained 32,294 candidates (mean age, 53 years; 74%, men); 27,200 made up the prepolicy training set and 5,094 were included in the postpolicy test set.

The team evaluated the accuracy of the six-status system using Harrell’s C-index and log-rank tests of Kaplan-Meier estimated survival by status for candidates listed after the policy change (November 2018 to March 2020) in the Scientific Registry of Transplant Recipients data set.

They then developed Cox proportional hazards models and random survival forest models using prepolicy data (2010-2017). Predictor variables included age, diagnosis, laboratory measurements, hemodynamics, and supportive treatment at the time of listing.

They found that the six-status ranking at listing has had “moderate ability” to rank order candidates.

As Dr. Parker indicated, statuses four and six had no significant difference in survival, and status five had lower survival than status four.

The investigators’ multivariable prediction models derived with prepolicy data ranked candidates correctly more often than the six-status rankings. Objective physiologic measurements, such as GFR and ECMO, were identified as having significant importance with regard to ranking by urgency.

“The novel prediction models we developed … could be implemented by the Organ Procurement and Transplantation Network (OPTN) as allocation policy and would be better than the status quo,” Dr. Parker said. “However, I think we could do even better using the newer data collected after 2018.” 
 

Modifications underway

The OPTN Heart Transplantation Committee is currently working on developing a new framework for allocating deceased donor hearts called Continuous Distribution.

“The six-tiered system works well, and it better stratifies the most medically urgent candidates than the previous allocation framework,” the leadership of the United Network for Organ Sharing Heart Transplantation Committee, including Chair Richard C. Daly, MD, Mayo Clinic; Vice-Chair Jondavid Menteer, MD, University of Southern California, Los Angeles; and former Chair Shelley Hall, MD, Baylor University Medical Center, told this news organization.

“That said, it is always appropriate to review and adjust variables that affect the medical urgency attribute for heart allocation.”

The new framework will change how patients are prioritized, they said. “Continuous distribution will consider all patient factors, including medical urgency, together to determine the order of an organ offer, and no single factor will decide an organ match.

“The goal is to increase fairness by moving to a points-based allocation framework that allows candidates to be compared using a single score composed of multiple factors.

“Furthermore,” they added, “continuous distribution provides a framework that will allow modifications of the criteria defining medical urgency (and other attributes of allocation) to a finer degree than the current policy. … Once continuous distribution is in place and the OPTN has policy monitoring data, the committee may consider and model different ways of defining medical urgency.”

Kiran K. Khush, MD, of Stanford (Calif.) University School of Medicine, coauthor of a related commentary, elaborated. “The composite allocation score (CAS) will consist of a ‘points-based system,’ in which candidates will be assigned points based on (1) medical urgency, (2) anticipated posttransplant survival, (3) candidate biology (eg., special characteristics that may result in higher prioritization, such as blood type O and allosensitization), (4) access (eg., prior living donor, pediatric patient), and (5) placement efficacy (travel, proximity).”

Candidates will be assigned points based on these categories, and will be rank ordered for each donor offer.

Dr. Khush and colleagues propose that a multivariable model – such as the ones described in the study – would be the best way to assign points for medical urgency.

“This system will be more equitable than the current system,” Dr. Khush said, “because it will better prioritize the sickest candidates while improving access for patients who are currently at a disadvantage [for example, blood O, highly sensitized patients], and will also remove artificial geographic boundaries [for example, the current 500-mile rule for heart allocation].”
 

Going further

Jesse D. Schold, PhD, of the University of Colorado at Denver, Aurora, raises concerns about other aspects of the heart allocation system in another related commentary.

“One big issue with our data in transplantation … is that, while it is very comprehensive for capturing transplant candidates and recipients, there is no data collection for patients and processes of care for patients prior to wait list placement,” he told this news organization. This phase of care is subject to wide variation in practice, he said, “and is likely as important as any to patients – the ability to be referred, evaluated, and placed on a waiting list.”

Report cards that measure quality of care after wait list placement ignore key phases prior to wait list placement, he said. “This may have the unintended consequences of limiting access to care and to the waiting list for patients perceived to be at higher risk, or the use of higher-risk donors, despite their potential survival advantage.

“In contrast,” he said, “quality report cards that incentivize treatment for all patients who may benefit would likely have a greater beneficial impact on patients with end-organ disease.”

There is also significant risk of underlying differences in patient populations between centers, despite the use of multivariable models, he added. This heterogeneity “may not be reflected accurately in the report cards [which] have significant impact for regulatory review, private payer contracting, and center reputation.”

Some of these concerns may be addressed in the new OPTN Modernization Initiative, according to David Bowman, a public affairs specialist at the Health Resources and Services Administration. One of the goals of the initiative “is to ensure that the OPTN Board of Directors is high functioning, has greater independence, and represents the diversity of communities served by the OPTN,” he told this news organization. “Strengthened governance will lead to effective policy development and implementation, and enhanced transparency and accountability of the process.”

Addressing another concern about the system, Savitri Fedson, MD, of the Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, wonders in a related editorial whether organ donors and recipients should know more about each other, and if so, could that reverse the ongoing downward trend in organ acceptance?

Although some organizations are in favor of sharing more information, Dr. Fedson notes that “less information may have the greater benefit.” She writes, “We might realize that the simplest approach is often the best: a fulsome thank you for the donor’s gift that is willingly given to a stranger without expectation of payment, and on the recipient side, the knowledge that an organ is of good quality.

“The transplant patient can be comforted with the understanding that the risk of disease transmission, while not zero, is low, and that their survival following acceptance of an organ is better than languishing on a waiting list.”

The study received no commercial funding. Dr. Parker, Dr. Khush, Dr. Schold, and Dr. Fedson report no relevant financial relationships.

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

BARCELONA – Staged hybrid ablation provided superior freedom from atrial arrhythmias compared with endocardial catheter ablation alone, including the need for repeat ablations in patients with advanced atrial fibrillation (AF), new data show.

“We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase, so this is a huge difference,” concluded cardiac surgeon Nicholas Doll, MD, PhD, Schüchtermann Clinic, Bad Rothenfelde, Germany.

Dr. Doll presented the 12-month follow up results of the Combined Endoscopic Epicardial and Percutaneous Endocardial Ablation Versus Repeated Catheter Ablation in Persistent and Longstanding Persistent Atrial Fibrillation (CEASE-AF) trial at the European Heart Rhythm Association 2023 Congress, held recently in Barcelona and virtually.

He said CEASE-AF is the largest multicenter randomized clinical trial comparing these two approaches for control of atrial arrhythmias.

Safety outcomes were numerically higher in the hybrid ablation (HA) group of the trial but not statistically different from the catheter ablation (CA) group.
 

Unstable wavefront

As background, Dr. Doll explained that in advanced AF, there is a high degree of endocardial-epicardial dissociation with unstable wavefront propagation transitioning between the endocardial and epicardial surfaces. Endocardial mapping and ablation alone may be insufficient to address the mechanism of AF.

“So, the hypothesis of the CEASE-AF study was a minimally invasive hybrid ablation approach which combines endocardial and epicardial ablation to achieve superior effectiveness when compared to endocardial catheter ablation alone,” he said.

This prospective clinical trial randomized patients 2:1 at nine sites in five countries to HA (n = 102) or CA (n = 52). All had left atrial diameter of 4 cm to 6 cm and persistent AF for up to 1 year or longstanding persistent AF for greater than 1 year up to 10 years.

Any patient with a previous ablation procedure, BMI greater than 35 kg/m², or left ventricular ejection fraction less than 30% was excluded.

For HA, stage 1 consisted of epicardial lesions for pulmonary vein isolation (PVI) plus the posterior wall box plus left atrial appendage exclusion using the AtriClip (AtriCure Inc.) left atrial appendage exclusion device. Stage 2 involved endocardial mapping and catheter ablation to address gaps.

For CA, the index procedure involved catheter-mediated PVI plus repeat endocardial ablation as clinically indicated. For both HA and CA, additional ablation techniques and lesions were allowed for nonparoxysmal AF.

The HA timeline was the first stage, index procedure at time 0 (n = 102), a 90-day blanking period, and then the second stage, endocardial procedure at 90 to 180 days from the index procedure (n = 93).

For the CA arm of the trial, endocardial catheter ablation was performed on a minimal endocardial lesion set at time 0. Then after a 90-day blanking period, repeat catheter ablation was performed if clinically indicated (6/52).

Repeat ablations and electrical or pharmaceutical cardioversions were allowed during the 12-month follow-up period from time 0.

The primary efficacy endpoint was freedom from AF, atrial flutter, or atrial tachycardia of greater than 30 seconds through 12 months in the absence of class I/III antiarrhythmic drugs except ones that previously had failed, at doses not exceeding those previously failed doses. The safety endpoint was a composite rate of major complications over the course of the study.

Even with relatively modest cohort sizes, the HA and CA arms of the trial were well matched at baseline for age (approximately 60 years), gender (75.5% and 73.1% male, respectively), BMI (29.7 and 29.8 kg/m²), and persistent AF (79.4% and 82.7%).

The groups had persistent AF for 2.94 ± 3.29 years and 3.34 ± 3.52 years, respectively. The mean left atrial size was 4.7 ± 0.5 cm for the HA group and 4.7 ± 0.4 cm for the CA group.

Outcomes favored hybrid ablation over catheter ablation, the researchers reported. “We never would have expected these huge differences,” Dr. Doll told the congress. “We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase.”

‘Exceptional’ trial

After Dr. Doll’s presentation, appointed discussant Stylianos Tzeis, MD, PhD, head of the cardiology clinic and electrophysiology and pacing department at Mitera Hospital in Athens, congratulated the investigators and called CEASE-AF “an exceptional trial. It was really challenging to enroll patients in such a randomized controlled clinical trial.”

But Dr. Tzeis questioned whether pitting CA against HA was a fair comparison.

“Were the ablation targets similar between the two groups?” he asked. He noted that for the HA group, in the first stage the patients had PVI, posterior wall isolation, exclusion of the left atrial appendage, and additional lesions at the discretion of the operator. Ninety percent proceeded to the second stage, which was endocardial catheter ablation with verification of posterior wall isolation and PVI and additional lesions made if needed.

In the CA group, repeat catheter ablation could be performed after the 90-day blanking period if clinically indicated. “Please take note that only 10% were offered the second ablation. So at least in my perspective, this was a comparison of a two-stage approach versus a single-stage approach with a much more aggressive ablation protocol in the hybrid ablation group as compared to the endocardial group,” he said.

Seeing the higher success rate of the HA group in achieving the primary efficacy endpoint of freedom from all arrhythmias at 12 months, Dr. Tzeis asked, “Does this reflect the superiority of the epi-endo approach, or does it reflect the suboptimal performance of the catheter ablation approach?”

There was a 40% success rate in the CA patient population, a cohort that he deemed “not the most challenging persistent AF population in the world”: those with left atrial diameter of 47 millimeters and with 80% having an AF duration less than 12 months.

He also noted that “the average duration of the catheter ablation for the PVI in the vast majority of cases was 4 hours, which does not reflect what really happens in the everyday practice.”

All those critiques having been advanced, Dr. Tzeis said, “Definitely do not doubt my first comment that the authors should be congratulated, and I strongly believe that the main objective has been achieved to bring electrophysiologist and cardiac surgeons ... closer.”

The study sponsor was AtriCure Inc. with collaboration of Cardialysis BV. Doll has received consulting fees or royalties and/or has ownership or stockholder interest in AtriCure. Tzeis reports no relevant financial relationships.
 

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

BARCELONA – Staged hybrid ablation provided superior freedom from atrial arrhythmias compared with endocardial catheter ablation alone, including the need for repeat ablations in patients with advanced atrial fibrillation (AF), new data show.

“We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase, so this is a huge difference,” concluded cardiac surgeon Nicholas Doll, MD, PhD, Schüchtermann Clinic, Bad Rothenfelde, Germany.

Dr. Doll presented the 12-month follow up results of the Combined Endoscopic Epicardial and Percutaneous Endocardial Ablation Versus Repeated Catheter Ablation in Persistent and Longstanding Persistent Atrial Fibrillation (CEASE-AF) trial at the European Heart Rhythm Association 2023 Congress, held recently in Barcelona and virtually.

He said CEASE-AF is the largest multicenter randomized clinical trial comparing these two approaches for control of atrial arrhythmias.

Safety outcomes were numerically higher in the hybrid ablation (HA) group of the trial but not statistically different from the catheter ablation (CA) group.
 

Unstable wavefront

As background, Dr. Doll explained that in advanced AF, there is a high degree of endocardial-epicardial dissociation with unstable wavefront propagation transitioning between the endocardial and epicardial surfaces. Endocardial mapping and ablation alone may be insufficient to address the mechanism of AF.

“So, the hypothesis of the CEASE-AF study was a minimally invasive hybrid ablation approach which combines endocardial and epicardial ablation to achieve superior effectiveness when compared to endocardial catheter ablation alone,” he said.

This prospective clinical trial randomized patients 2:1 at nine sites in five countries to HA (n = 102) or CA (n = 52). All had left atrial diameter of 4 cm to 6 cm and persistent AF for up to 1 year or longstanding persistent AF for greater than 1 year up to 10 years.

Any patient with a previous ablation procedure, BMI greater than 35 kg/m², or left ventricular ejection fraction less than 30% was excluded.

For HA, stage 1 consisted of epicardial lesions for pulmonary vein isolation (PVI) plus the posterior wall box plus left atrial appendage exclusion using the AtriClip (AtriCure Inc.) left atrial appendage exclusion device. Stage 2 involved endocardial mapping and catheter ablation to address gaps.

For CA, the index procedure involved catheter-mediated PVI plus repeat endocardial ablation as clinically indicated. For both HA and CA, additional ablation techniques and lesions were allowed for nonparoxysmal AF.

The HA timeline was the first stage, index procedure at time 0 (n = 102), a 90-day blanking period, and then the second stage, endocardial procedure at 90 to 180 days from the index procedure (n = 93).

For the CA arm of the trial, endocardial catheter ablation was performed on a minimal endocardial lesion set at time 0. Then after a 90-day blanking period, repeat catheter ablation was performed if clinically indicated (6/52).

Repeat ablations and electrical or pharmaceutical cardioversions were allowed during the 12-month follow-up period from time 0.

The primary efficacy endpoint was freedom from AF, atrial flutter, or atrial tachycardia of greater than 30 seconds through 12 months in the absence of class I/III antiarrhythmic drugs except ones that previously had failed, at doses not exceeding those previously failed doses. The safety endpoint was a composite rate of major complications over the course of the study.

Even with relatively modest cohort sizes, the HA and CA arms of the trial were well matched at baseline for age (approximately 60 years), gender (75.5% and 73.1% male, respectively), BMI (29.7 and 29.8 kg/m²), and persistent AF (79.4% and 82.7%).

The groups had persistent AF for 2.94 ± 3.29 years and 3.34 ± 3.52 years, respectively. The mean left atrial size was 4.7 ± 0.5 cm for the HA group and 4.7 ± 0.4 cm for the CA group.

Outcomes favored hybrid ablation over catheter ablation, the researchers reported. “We never would have expected these huge differences,” Dr. Doll told the congress. “We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase.”

‘Exceptional’ trial

After Dr. Doll’s presentation, appointed discussant Stylianos Tzeis, MD, PhD, head of the cardiology clinic and electrophysiology and pacing department at Mitera Hospital in Athens, congratulated the investigators and called CEASE-AF “an exceptional trial. It was really challenging to enroll patients in such a randomized controlled clinical trial.”

But Dr. Tzeis questioned whether pitting CA against HA was a fair comparison.

“Were the ablation targets similar between the two groups?” he asked. He noted that for the HA group, in the first stage the patients had PVI, posterior wall isolation, exclusion of the left atrial appendage, and additional lesions at the discretion of the operator. Ninety percent proceeded to the second stage, which was endocardial catheter ablation with verification of posterior wall isolation and PVI and additional lesions made if needed.

In the CA group, repeat catheter ablation could be performed after the 90-day blanking period if clinically indicated. “Please take note that only 10% were offered the second ablation. So at least in my perspective, this was a comparison of a two-stage approach versus a single-stage approach with a much more aggressive ablation protocol in the hybrid ablation group as compared to the endocardial group,” he said.

Seeing the higher success rate of the HA group in achieving the primary efficacy endpoint of freedom from all arrhythmias at 12 months, Dr. Tzeis asked, “Does this reflect the superiority of the epi-endo approach, or does it reflect the suboptimal performance of the catheter ablation approach?”

There was a 40% success rate in the CA patient population, a cohort that he deemed “not the most challenging persistent AF population in the world”: those with left atrial diameter of 47 millimeters and with 80% having an AF duration less than 12 months.

He also noted that “the average duration of the catheter ablation for the PVI in the vast majority of cases was 4 hours, which does not reflect what really happens in the everyday practice.”

All those critiques having been advanced, Dr. Tzeis said, “Definitely do not doubt my first comment that the authors should be congratulated, and I strongly believe that the main objective has been achieved to bring electrophysiologist and cardiac surgeons ... closer.”

The study sponsor was AtriCure Inc. with collaboration of Cardialysis BV. Doll has received consulting fees or royalties and/or has ownership or stockholder interest in AtriCure. Tzeis reports no relevant financial relationships.
 

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

BARCELONA – Staged hybrid ablation provided superior freedom from atrial arrhythmias compared with endocardial catheter ablation alone, including the need for repeat ablations in patients with advanced atrial fibrillation (AF), new data show.

“We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase, so this is a huge difference,” concluded cardiac surgeon Nicholas Doll, MD, PhD, Schüchtermann Clinic, Bad Rothenfelde, Germany.

Dr. Doll presented the 12-month follow up results of the Combined Endoscopic Epicardial and Percutaneous Endocardial Ablation Versus Repeated Catheter Ablation in Persistent and Longstanding Persistent Atrial Fibrillation (CEASE-AF) trial at the European Heart Rhythm Association 2023 Congress, held recently in Barcelona and virtually.

He said CEASE-AF is the largest multicenter randomized clinical trial comparing these two approaches for control of atrial arrhythmias.

Safety outcomes were numerically higher in the hybrid ablation (HA) group of the trial but not statistically different from the catheter ablation (CA) group.
 

Unstable wavefront

As background, Dr. Doll explained that in advanced AF, there is a high degree of endocardial-epicardial dissociation with unstable wavefront propagation transitioning between the endocardial and epicardial surfaces. Endocardial mapping and ablation alone may be insufficient to address the mechanism of AF.

“So, the hypothesis of the CEASE-AF study was a minimally invasive hybrid ablation approach which combines endocardial and epicardial ablation to achieve superior effectiveness when compared to endocardial catheter ablation alone,” he said.

This prospective clinical trial randomized patients 2:1 at nine sites in five countries to HA (n = 102) or CA (n = 52). All had left atrial diameter of 4 cm to 6 cm and persistent AF for up to 1 year or longstanding persistent AF for greater than 1 year up to 10 years.

Any patient with a previous ablation procedure, BMI greater than 35 kg/m², or left ventricular ejection fraction less than 30% was excluded.

For HA, stage 1 consisted of epicardial lesions for pulmonary vein isolation (PVI) plus the posterior wall box plus left atrial appendage exclusion using the AtriClip (AtriCure Inc.) left atrial appendage exclusion device. Stage 2 involved endocardial mapping and catheter ablation to address gaps.

For CA, the index procedure involved catheter-mediated PVI plus repeat endocardial ablation as clinically indicated. For both HA and CA, additional ablation techniques and lesions were allowed for nonparoxysmal AF.

The HA timeline was the first stage, index procedure at time 0 (n = 102), a 90-day blanking period, and then the second stage, endocardial procedure at 90 to 180 days from the index procedure (n = 93).

For the CA arm of the trial, endocardial catheter ablation was performed on a minimal endocardial lesion set at time 0. Then after a 90-day blanking period, repeat catheter ablation was performed if clinically indicated (6/52).

Repeat ablations and electrical or pharmaceutical cardioversions were allowed during the 12-month follow-up period from time 0.

The primary efficacy endpoint was freedom from AF, atrial flutter, or atrial tachycardia of greater than 30 seconds through 12 months in the absence of class I/III antiarrhythmic drugs except ones that previously had failed, at doses not exceeding those previously failed doses. The safety endpoint was a composite rate of major complications over the course of the study.

Even with relatively modest cohort sizes, the HA and CA arms of the trial were well matched at baseline for age (approximately 60 years), gender (75.5% and 73.1% male, respectively), BMI (29.7 and 29.8 kg/m²), and persistent AF (79.4% and 82.7%).

The groups had persistent AF for 2.94 ± 3.29 years and 3.34 ± 3.52 years, respectively. The mean left atrial size was 4.7 ± 0.5 cm for the HA group and 4.7 ± 0.4 cm for the CA group.

Outcomes favored hybrid ablation over catheter ablation, the researchers reported. “We never would have expected these huge differences,” Dr. Doll told the congress. “We have seen that hybrid ablation resulted in 32.4% absolute benefit increase in effectiveness and 83% relative benefit increase.”

‘Exceptional’ trial

After Dr. Doll’s presentation, appointed discussant Stylianos Tzeis, MD, PhD, head of the cardiology clinic and electrophysiology and pacing department at Mitera Hospital in Athens, congratulated the investigators and called CEASE-AF “an exceptional trial. It was really challenging to enroll patients in such a randomized controlled clinical trial.”

But Dr. Tzeis questioned whether pitting CA against HA was a fair comparison.

“Were the ablation targets similar between the two groups?” he asked. He noted that for the HA group, in the first stage the patients had PVI, posterior wall isolation, exclusion of the left atrial appendage, and additional lesions at the discretion of the operator. Ninety percent proceeded to the second stage, which was endocardial catheter ablation with verification of posterior wall isolation and PVI and additional lesions made if needed.

In the CA group, repeat catheter ablation could be performed after the 90-day blanking period if clinically indicated. “Please take note that only 10% were offered the second ablation. So at least in my perspective, this was a comparison of a two-stage approach versus a single-stage approach with a much more aggressive ablation protocol in the hybrid ablation group as compared to the endocardial group,” he said.

Seeing the higher success rate of the HA group in achieving the primary efficacy endpoint of freedom from all arrhythmias at 12 months, Dr. Tzeis asked, “Does this reflect the superiority of the epi-endo approach, or does it reflect the suboptimal performance of the catheter ablation approach?”

There was a 40% success rate in the CA patient population, a cohort that he deemed “not the most challenging persistent AF population in the world”: those with left atrial diameter of 47 millimeters and with 80% having an AF duration less than 12 months.

He also noted that “the average duration of the catheter ablation for the PVI in the vast majority of cases was 4 hours, which does not reflect what really happens in the everyday practice.”

All those critiques having been advanced, Dr. Tzeis said, “Definitely do not doubt my first comment that the authors should be congratulated, and I strongly believe that the main objective has been achieved to bring electrophysiologist and cardiac surgeons ... closer.”

The study sponsor was AtriCure Inc. with collaboration of Cardialysis BV. Doll has received consulting fees or royalties and/or has ownership or stockholder interest in AtriCure. Tzeis reports no relevant financial relationships.
 

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

In a new scientific statement, the American Heart Association highlighted the importance of incorporating nonbiological risk factors and social determinants of health in cardiovascular disease (CVD) risk assessment for women, particularly women from different racial and ethnic backgrounds.
 

CVD risk assessment in women is multifaceted and goes well beyond traditional risk factors to include sex-specific biological risk factors, as well as social, behavioral, and environmental factors, the writing group noted.

They said a greater focus on addressing all CVD risk factors among women from underrepresented races and ethnicities is warranted to avert future CVD.

The scientific statement was published online in Circulation.
 

Look beyond traditional risk factors

“Risk assessment is the first step in preventing heart disease, yet there are many limitations to traditional risk factors and their ability to comprehensively estimate a woman’s risk for cardiovascular disease,” Jennifer H. Mieres, MD, vice chair of the writing group and professor of cardiology at Hofstra University, Hempstead, N.Y., said in a news release. 

“The delivery of equitable cardiovascular health care for women depends on improving the knowledge and awareness of all members of the healthcare team about the full spectrum of cardiovascular risk factors for women, including female-specific and female-predominant risk factors,” Dr. Mieres added.

Female-specific factors that should be included in CVD risk assessment include pregnancy-related conditions such as preeclampsia, preterm delivery, and gestational diabetes, the writing group said.

Other factors include menstrual cycle history; types of birth control and/or hormone replacement therapy used; polycystic ovarian syndrome (PCOS), which affects 10% of women of reproductive age and is associated with increased CVD risk; and autoimmune disorders, depression, and PTSD, all of which are more common in women and are also associated with higher risk for CVD.

The statement also highlights the key role that social determinants of health (SDOH) play in the development of CVD in women, particularly women from diverse racial and ethnic backgrounds. SDOH include education level, economic stability, neighborhood safety, working conditions, environmental hazards, and access to quality health care.

“It is critical that risk assessment be expanded to include [SDOH] as risk factors if we are to improve health outcomes in all women,” Laxmi Mehta, MD, chair of the writing group and director of preventative cardiology and women’s cardiovascular health at Ohio State University Wexner Medical Center, Columbus, said in the news release.

“It is also important for the health care team to consider [SDOH] when working with women on shared decisions about cardiovascular disease prevention and treatment,” Dr. Mehta noted.
 

No one-size-fits-all approach

The statement highlighted significant differences in CVD risk among women of different racial and ethnic backgrounds and provides detailed CV risk factor profiles for non-Hispanic Black, Hispanic/Latinx, Asian and American Indian/Alaska Native women.

It noted that language barriers, discrimination, acculturation, and health care access disproportionately affect women of underrepresented racial and ethnic groups. These factors result in a higher prevalence of CVD and significant challenges in CVD diagnosis and treatment.

“When customizing CVD prevention and treatment strategies to improve cardiovascular health for women, a one-size-fits-all approach is unlikely to be successful,” Dr. Mieres said.

“We must be cognizant of the complex interplay of sex, race and ethnicity, as well as social determinants of health, and how they impact the risk of cardiovascular disease and adverse outcomes in order to avert future CVD morbidity and mortality,” Dr. Mieres added.

Looking ahead, the writing group said future CVD prevention guidelines could be strengthened by including culturally-specific lifestyle recommendations.

They also said community-based approaches, faith-based community partnerships, and peer support to encourage a healthy lifestyle could play a key role in preventing CVD among all women.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Cardiovascular Disease and Stroke in Women and Underrepresented Populations Committee of the Council on Clinical Cardiology, the Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifelong Congenital Heart Disease and Heart Health in the Young, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.

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

In a new scientific statement, the American Heart Association highlighted the importance of incorporating nonbiological risk factors and social determinants of health in cardiovascular disease (CVD) risk assessment for women, particularly women from different racial and ethnic backgrounds.
 

CVD risk assessment in women is multifaceted and goes well beyond traditional risk factors to include sex-specific biological risk factors, as well as social, behavioral, and environmental factors, the writing group noted.

They said a greater focus on addressing all CVD risk factors among women from underrepresented races and ethnicities is warranted to avert future CVD.

The scientific statement was published online in Circulation.
 

Look beyond traditional risk factors

“Risk assessment is the first step in preventing heart disease, yet there are many limitations to traditional risk factors and their ability to comprehensively estimate a woman’s risk for cardiovascular disease,” Jennifer H. Mieres, MD, vice chair of the writing group and professor of cardiology at Hofstra University, Hempstead, N.Y., said in a news release. 

“The delivery of equitable cardiovascular health care for women depends on improving the knowledge and awareness of all members of the healthcare team about the full spectrum of cardiovascular risk factors for women, including female-specific and female-predominant risk factors,” Dr. Mieres added.

Female-specific factors that should be included in CVD risk assessment include pregnancy-related conditions such as preeclampsia, preterm delivery, and gestational diabetes, the writing group said.

Other factors include menstrual cycle history; types of birth control and/or hormone replacement therapy used; polycystic ovarian syndrome (PCOS), which affects 10% of women of reproductive age and is associated with increased CVD risk; and autoimmune disorders, depression, and PTSD, all of which are more common in women and are also associated with higher risk for CVD.

The statement also highlights the key role that social determinants of health (SDOH) play in the development of CVD in women, particularly women from diverse racial and ethnic backgrounds. SDOH include education level, economic stability, neighborhood safety, working conditions, environmental hazards, and access to quality health care.

“It is critical that risk assessment be expanded to include [SDOH] as risk factors if we are to improve health outcomes in all women,” Laxmi Mehta, MD, chair of the writing group and director of preventative cardiology and women’s cardiovascular health at Ohio State University Wexner Medical Center, Columbus, said in the news release.

“It is also important for the health care team to consider [SDOH] when working with women on shared decisions about cardiovascular disease prevention and treatment,” Dr. Mehta noted.
 

No one-size-fits-all approach

The statement highlighted significant differences in CVD risk among women of different racial and ethnic backgrounds and provides detailed CV risk factor profiles for non-Hispanic Black, Hispanic/Latinx, Asian and American Indian/Alaska Native women.

It noted that language barriers, discrimination, acculturation, and health care access disproportionately affect women of underrepresented racial and ethnic groups. These factors result in a higher prevalence of CVD and significant challenges in CVD diagnosis and treatment.

“When customizing CVD prevention and treatment strategies to improve cardiovascular health for women, a one-size-fits-all approach is unlikely to be successful,” Dr. Mieres said.

“We must be cognizant of the complex interplay of sex, race and ethnicity, as well as social determinants of health, and how they impact the risk of cardiovascular disease and adverse outcomes in order to avert future CVD morbidity and mortality,” Dr. Mieres added.

Looking ahead, the writing group said future CVD prevention guidelines could be strengthened by including culturally-specific lifestyle recommendations.

They also said community-based approaches, faith-based community partnerships, and peer support to encourage a healthy lifestyle could play a key role in preventing CVD among all women.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Cardiovascular Disease and Stroke in Women and Underrepresented Populations Committee of the Council on Clinical Cardiology, the Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifelong Congenital Heart Disease and Heart Health in the Young, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.

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

In a new scientific statement, the American Heart Association highlighted the importance of incorporating nonbiological risk factors and social determinants of health in cardiovascular disease (CVD) risk assessment for women, particularly women from different racial and ethnic backgrounds.
 

CVD risk assessment in women is multifaceted and goes well beyond traditional risk factors to include sex-specific biological risk factors, as well as social, behavioral, and environmental factors, the writing group noted.

They said a greater focus on addressing all CVD risk factors among women from underrepresented races and ethnicities is warranted to avert future CVD.

The scientific statement was published online in Circulation.
 

Look beyond traditional risk factors

“Risk assessment is the first step in preventing heart disease, yet there are many limitations to traditional risk factors and their ability to comprehensively estimate a woman’s risk for cardiovascular disease,” Jennifer H. Mieres, MD, vice chair of the writing group and professor of cardiology at Hofstra University, Hempstead, N.Y., said in a news release. 

“The delivery of equitable cardiovascular health care for women depends on improving the knowledge and awareness of all members of the healthcare team about the full spectrum of cardiovascular risk factors for women, including female-specific and female-predominant risk factors,” Dr. Mieres added.

Female-specific factors that should be included in CVD risk assessment include pregnancy-related conditions such as preeclampsia, preterm delivery, and gestational diabetes, the writing group said.

Other factors include menstrual cycle history; types of birth control and/or hormone replacement therapy used; polycystic ovarian syndrome (PCOS), which affects 10% of women of reproductive age and is associated with increased CVD risk; and autoimmune disorders, depression, and PTSD, all of which are more common in women and are also associated with higher risk for CVD.

The statement also highlights the key role that social determinants of health (SDOH) play in the development of CVD in women, particularly women from diverse racial and ethnic backgrounds. SDOH include education level, economic stability, neighborhood safety, working conditions, environmental hazards, and access to quality health care.

“It is critical that risk assessment be expanded to include [SDOH] as risk factors if we are to improve health outcomes in all women,” Laxmi Mehta, MD, chair of the writing group and director of preventative cardiology and women’s cardiovascular health at Ohio State University Wexner Medical Center, Columbus, said in the news release.

“It is also important for the health care team to consider [SDOH] when working with women on shared decisions about cardiovascular disease prevention and treatment,” Dr. Mehta noted.
 

No one-size-fits-all approach

The statement highlighted significant differences in CVD risk among women of different racial and ethnic backgrounds and provides detailed CV risk factor profiles for non-Hispanic Black, Hispanic/Latinx, Asian and American Indian/Alaska Native women.

It noted that language barriers, discrimination, acculturation, and health care access disproportionately affect women of underrepresented racial and ethnic groups. These factors result in a higher prevalence of CVD and significant challenges in CVD diagnosis and treatment.

“When customizing CVD prevention and treatment strategies to improve cardiovascular health for women, a one-size-fits-all approach is unlikely to be successful,” Dr. Mieres said.

“We must be cognizant of the complex interplay of sex, race and ethnicity, as well as social determinants of health, and how they impact the risk of cardiovascular disease and adverse outcomes in order to avert future CVD morbidity and mortality,” Dr. Mieres added.

Looking ahead, the writing group said future CVD prevention guidelines could be strengthened by including culturally-specific lifestyle recommendations.

They also said community-based approaches, faith-based community partnerships, and peer support to encourage a healthy lifestyle could play a key role in preventing CVD among all women.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA’s Cardiovascular Disease and Stroke in Women and Underrepresented Populations Committee of the Council on Clinical Cardiology, the Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifelong Congenital Heart Disease and Heart Health in the Young, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.

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

The American Society of Echocardiography (ASE) has issued guidance on all critical aspects of training for cardiology and anesthesiology trainees and postgraduate echocardiographers who plan to specialize in interventional echocardiography (IE).

The guideline outlines requirements of the training institution, the duration and core competencies of training, minimal procedural volume for competency in IE, and knowledge of specific structural health disease (SHD) procedures.

The 16-page guideline was published online  in the Journal of the American Society of Echocardiography.
 

Specific skill set

IE is the primary imaging modality used to support and guide SHD interventions, such as heart valve replacements and other cardiac catheterization procedures, the writing group notes.

They say the “emerging specialty” of IE requires a specific set of skills to support an array of transcatheter therapies, with successful outcomes highly dependent on the skill of the echocardiography team.

“IE techniques are unique since imaging is performed in real-time, it is highly dependent on 3D and non-standard views, and it has immediate and profound implications for patient management,” Stephen H. Little, MD, ASE president and co-chair of the guideline writing group, says in a news release.

“Additionally, IE requires candid, accurate, and timely communication with other members of the multidisciplinary SHD team,” Dr. Little adds.

The new ASE guideline expands on the 2019 statement on echocardiography training put forward by the American College of Cardiology, American Heart Association, and ASE, by focusing specifically on interventional echocardiographers.

It outlines core competencies common to all transcatheter therapies, as well as specific transcatheter procedures. It provides consensus recommendations for specific knowledge, experience, and skills to be learned and demonstrated within an IE training program or during postgraduate training.

A “core principle” in the guideline states that the length of IE training or achieved number of procedures performed are less important than the demonstration of procedure-specific competencies within the milestone domains of knowledge, skill, and communication.

“Transcatheter therapies for SHD continue to grow at a rapid pace, which means that the demand for skilled interventional echocardiographers has steadily increased,” Vera H. Rigolin, MD, co-chair of the guideline writing, says in the release.

“Training standards are needed to ensure that interventional echocardiographers have the necessary expertise to provide fast, accurate, and high-quality image acquisition and interpretation in real-time,” Dr. Rigolin adds.

In addition, the guidelines states that use of simulation training has a role in IE training.

Virtual and simulation training could shorten the learning curve for trainees and, when combined with remote learning, could permit societies to standardize a teaching curriculum and allow the trainee to complete training in a reasonable timeframe. Simulator training may also improve access to training and thus promote diversity and inclusivity, the writing group says.

The guideline has been endorsed by 21 ASE international partners.

Writing group co-chairs Little and Rigolin have declared no conflicts of interest. A complete list of disclosures for the writing group is available with the original article.

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

The American Society of Echocardiography (ASE) has issued guidance on all critical aspects of training for cardiology and anesthesiology trainees and postgraduate echocardiographers who plan to specialize in interventional echocardiography (IE).

The guideline outlines requirements of the training institution, the duration and core competencies of training, minimal procedural volume for competency in IE, and knowledge of specific structural health disease (SHD) procedures.

The 16-page guideline was published online  in the Journal of the American Society of Echocardiography.
 

Specific skill set

IE is the primary imaging modality used to support and guide SHD interventions, such as heart valve replacements and other cardiac catheterization procedures, the writing group notes.

They say the “emerging specialty” of IE requires a specific set of skills to support an array of transcatheter therapies, with successful outcomes highly dependent on the skill of the echocardiography team.

“IE techniques are unique since imaging is performed in real-time, it is highly dependent on 3D and non-standard views, and it has immediate and profound implications for patient management,” Stephen H. Little, MD, ASE president and co-chair of the guideline writing group, says in a news release.

“Additionally, IE requires candid, accurate, and timely communication with other members of the multidisciplinary SHD team,” Dr. Little adds.

The new ASE guideline expands on the 2019 statement on echocardiography training put forward by the American College of Cardiology, American Heart Association, and ASE, by focusing specifically on interventional echocardiographers.

It outlines core competencies common to all transcatheter therapies, as well as specific transcatheter procedures. It provides consensus recommendations for specific knowledge, experience, and skills to be learned and demonstrated within an IE training program or during postgraduate training.

A “core principle” in the guideline states that the length of IE training or achieved number of procedures performed are less important than the demonstration of procedure-specific competencies within the milestone domains of knowledge, skill, and communication.

“Transcatheter therapies for SHD continue to grow at a rapid pace, which means that the demand for skilled interventional echocardiographers has steadily increased,” Vera H. Rigolin, MD, co-chair of the guideline writing, says in the release.

“Training standards are needed to ensure that interventional echocardiographers have the necessary expertise to provide fast, accurate, and high-quality image acquisition and interpretation in real-time,” Dr. Rigolin adds.

In addition, the guidelines states that use of simulation training has a role in IE training.

Virtual and simulation training could shorten the learning curve for trainees and, when combined with remote learning, could permit societies to standardize a teaching curriculum and allow the trainee to complete training in a reasonable timeframe. Simulator training may also improve access to training and thus promote diversity and inclusivity, the writing group says.

The guideline has been endorsed by 21 ASE international partners.

Writing group co-chairs Little and Rigolin have declared no conflicts of interest. A complete list of disclosures for the writing group is available with the original article.

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

The American Society of Echocardiography (ASE) has issued guidance on all critical aspects of training for cardiology and anesthesiology trainees and postgraduate echocardiographers who plan to specialize in interventional echocardiography (IE).

The guideline outlines requirements of the training institution, the duration and core competencies of training, minimal procedural volume for competency in IE, and knowledge of specific structural health disease (SHD) procedures.

The 16-page guideline was published online  in the Journal of the American Society of Echocardiography.
 

Specific skill set

IE is the primary imaging modality used to support and guide SHD interventions, such as heart valve replacements and other cardiac catheterization procedures, the writing group notes.

They say the “emerging specialty” of IE requires a specific set of skills to support an array of transcatheter therapies, with successful outcomes highly dependent on the skill of the echocardiography team.

“IE techniques are unique since imaging is performed in real-time, it is highly dependent on 3D and non-standard views, and it has immediate and profound implications for patient management,” Stephen H. Little, MD, ASE president and co-chair of the guideline writing group, says in a news release.

“Additionally, IE requires candid, accurate, and timely communication with other members of the multidisciplinary SHD team,” Dr. Little adds.

The new ASE guideline expands on the 2019 statement on echocardiography training put forward by the American College of Cardiology, American Heart Association, and ASE, by focusing specifically on interventional echocardiographers.

It outlines core competencies common to all transcatheter therapies, as well as specific transcatheter procedures. It provides consensus recommendations for specific knowledge, experience, and skills to be learned and demonstrated within an IE training program or during postgraduate training.

A “core principle” in the guideline states that the length of IE training or achieved number of procedures performed are less important than the demonstration of procedure-specific competencies within the milestone domains of knowledge, skill, and communication.

“Transcatheter therapies for SHD continue to grow at a rapid pace, which means that the demand for skilled interventional echocardiographers has steadily increased,” Vera H. Rigolin, MD, co-chair of the guideline writing, says in the release.

“Training standards are needed to ensure that interventional echocardiographers have the necessary expertise to provide fast, accurate, and high-quality image acquisition and interpretation in real-time,” Dr. Rigolin adds.

In addition, the guidelines states that use of simulation training has a role in IE training.

Virtual and simulation training could shorten the learning curve for trainees and, when combined with remote learning, could permit societies to standardize a teaching curriculum and allow the trainee to complete training in a reasonable timeframe. Simulator training may also improve access to training and thus promote diversity and inclusivity, the writing group says.

The guideline has been endorsed by 21 ASE international partners.

Writing group co-chairs Little and Rigolin have declared no conflicts of interest. A complete list of disclosures for the writing group is available with the original article.

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

A round heart, or left ventricle sphericity, predicted cardiomyopathy and atrial fibrillation (AFib) in a deep learning analysis of MRI images from close to 39,000 participants in the UK Biobank, a new study shows.

An increase of 1 standard deviation in the sphericity index (short axis length/long axis length) was associated with a 47% increased incidence of cardiomyopathy and a 20% increased incidence of AFib, independent of clinical factors and traditional MRI measures.

Furthermore, a genetic analysis suggested a shared architecture between sphericity and nonischemic cardiomyopathy, pointing to NICM as a possible causal factor for left ventricle sphericity among individuals with normal LV size and function.

“Physicians have known the heart gets rounder after heart attacks and as we get older,” David Ouyang, MD, a cardiologist in the Smidt Heart Institute at Cedars-Sinai Medical Center, Los Angeles, and a researcher in the division of artificial intelligence in medicine, said in an interview. “We wanted to see if this sphericity is prognostic of future disease even in healthy individuals.”

Although it is too early to recommend heart shape assessment in healthy asymptomatic people, he said, “physicians should be extra careful and think about treatments when they notice a patient’s heart is particularly round.”

The study was published online March 29 in the journal Med.
 

Sphericity index key

The investigators hypothesized that there is variation in LV sphericity within the spectrum of normal LV chamber size and systolic function, and that such variation might be a marker of cardiac risk with genetic influences.

To test this hypothesis, they used automated deep-learning segmentation of cardiac MRI data to estimate and analyze the sphericity index in a cohort of 38,897 individuals participating in the UK Biobank.

After adjustment for age at MRI and sex, an increased sphericity index was associated with an increased risk for cardiomyopathy (hazard ratio, 1.57), AFib (HR, 1.35), and heart failure (HR, 1.37).

No significant association was seen with cardiac arrest.

The team then stratified the cohort into quintiles and compared the top 20%, middle 60%, and bottom 20%. The relationship between the sphericity index and risk extended across the distribution; individuals with higher than median sphericity had increased disease incidence, and those with lower than median sphericity had decreased incidence.

Overall, a single standard deviation in the sphericity index was associated with increased risk of cardiomyopathy (HR, 1.47) and of AFib (HR, 1.20), independent of clinical factors and usual MRI measurements.

In a minimally adjusted model, the sphericity index was a predictor of incident cardiomyopathy, AFib, and heart failure.

Adjustment for clinical factors partially attenuated the heart failure association; additional adjustment for MRI measurements fully attenuated that association and partially attenuated the association with AFib.

However, in all adjusted models, the association with cardiomyopathy showed little attenuation.

Furthermore, the team identified four loci associated with sphericity at genomewide significance – PLN, ANGPT1, PDZRN3, and HLA DR/DQ – and Mendelian randomization supported NICM as a cause of LV sphericity.
 

Looking ahead

“While conventional imaging metrics have significant diagnostic and prognostic value, some of these measurements have been adopted out of convenience or tradition,” the authors noted. “By representing a specific multidimensional remodeling phenotype, sphericity has emerged as a distinct morphologic trait with features not adequately captured by conventional measurements.

“We expect that the search space of potential imaging measurements is vast, and we have only begun to scratch at the surface of disease associations.”

Indeed, Dr. Ouyang said his group is “trying to evaluate the sphericity in echocardiograms or heart ultrasounds, which are more common and cheaper than MRI.”

“The main caveat is translating the information directly to patient care,” Richard C. Becker, MD, director and physician-in-chief of the University of Cincinnati Heart, Lung, and Vascular Institute, said in an interview. “Near-term yield could include using the spherical calculation in routine MRI of the heart, and based on the findings, following patients more closely if there is an abnormal shape. Or performing an MRI and targeted gene testing if there is a family history of cardiomyopathy or [of] an abnormal shape of the heart.”

“Validation of the findings and large-scale evaluation of the genes identified, and how they interact with patient and environmental factors, will be very important,” he added.

Nevertheless, “the study was well done and may serve as a foundation for future research,” Dr. Becker said. “The investigators used several powerful tools, including MRI, genomics, and [artificial intelligence] to draw their conclusions. This is precisely the way that ‘big data’ should be used – in a complementary fashion.”

The study authors and Dr. Becker reported no relevant financial relationships.

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

A round heart, or left ventricle sphericity, predicted cardiomyopathy and atrial fibrillation (AFib) in a deep learning analysis of MRI images from close to 39,000 participants in the UK Biobank, a new study shows.

An increase of 1 standard deviation in the sphericity index (short axis length/long axis length) was associated with a 47% increased incidence of cardiomyopathy and a 20% increased incidence of AFib, independent of clinical factors and traditional MRI measures.

Furthermore, a genetic analysis suggested a shared architecture between sphericity and nonischemic cardiomyopathy, pointing to NICM as a possible causal factor for left ventricle sphericity among individuals with normal LV size and function.

“Physicians have known the heart gets rounder after heart attacks and as we get older,” David Ouyang, MD, a cardiologist in the Smidt Heart Institute at Cedars-Sinai Medical Center, Los Angeles, and a researcher in the division of artificial intelligence in medicine, said in an interview. “We wanted to see if this sphericity is prognostic of future disease even in healthy individuals.”

Although it is too early to recommend heart shape assessment in healthy asymptomatic people, he said, “physicians should be extra careful and think about treatments when they notice a patient’s heart is particularly round.”

The study was published online March 29 in the journal Med.
 

Sphericity index key

The investigators hypothesized that there is variation in LV sphericity within the spectrum of normal LV chamber size and systolic function, and that such variation might be a marker of cardiac risk with genetic influences.

To test this hypothesis, they used automated deep-learning segmentation of cardiac MRI data to estimate and analyze the sphericity index in a cohort of 38,897 individuals participating in the UK Biobank.

After adjustment for age at MRI and sex, an increased sphericity index was associated with an increased risk for cardiomyopathy (hazard ratio, 1.57), AFib (HR, 1.35), and heart failure (HR, 1.37).

No significant association was seen with cardiac arrest.

The team then stratified the cohort into quintiles and compared the top 20%, middle 60%, and bottom 20%. The relationship between the sphericity index and risk extended across the distribution; individuals with higher than median sphericity had increased disease incidence, and those with lower than median sphericity had decreased incidence.

Overall, a single standard deviation in the sphericity index was associated with increased risk of cardiomyopathy (HR, 1.47) and of AFib (HR, 1.20), independent of clinical factors and usual MRI measurements.

In a minimally adjusted model, the sphericity index was a predictor of incident cardiomyopathy, AFib, and heart failure.

Adjustment for clinical factors partially attenuated the heart failure association; additional adjustment for MRI measurements fully attenuated that association and partially attenuated the association with AFib.

However, in all adjusted models, the association with cardiomyopathy showed little attenuation.

Furthermore, the team identified four loci associated with sphericity at genomewide significance – PLN, ANGPT1, PDZRN3, and HLA DR/DQ – and Mendelian randomization supported NICM as a cause of LV sphericity.
 

Looking ahead

“While conventional imaging metrics have significant diagnostic and prognostic value, some of these measurements have been adopted out of convenience or tradition,” the authors noted. “By representing a specific multidimensional remodeling phenotype, sphericity has emerged as a distinct morphologic trait with features not adequately captured by conventional measurements.

“We expect that the search space of potential imaging measurements is vast, and we have only begun to scratch at the surface of disease associations.”

Indeed, Dr. Ouyang said his group is “trying to evaluate the sphericity in echocardiograms or heart ultrasounds, which are more common and cheaper than MRI.”

“The main caveat is translating the information directly to patient care,” Richard C. Becker, MD, director and physician-in-chief of the University of Cincinnati Heart, Lung, and Vascular Institute, said in an interview. “Near-term yield could include using the spherical calculation in routine MRI of the heart, and based on the findings, following patients more closely if there is an abnormal shape. Or performing an MRI and targeted gene testing if there is a family history of cardiomyopathy or [of] an abnormal shape of the heart.”

“Validation of the findings and large-scale evaluation of the genes identified, and how they interact with patient and environmental factors, will be very important,” he added.

Nevertheless, “the study was well done and may serve as a foundation for future research,” Dr. Becker said. “The investigators used several powerful tools, including MRI, genomics, and [artificial intelligence] to draw their conclusions. This is precisely the way that ‘big data’ should be used – in a complementary fashion.”

The study authors and Dr. Becker reported no relevant financial relationships.

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

A round heart, or left ventricle sphericity, predicted cardiomyopathy and atrial fibrillation (AFib) in a deep learning analysis of MRI images from close to 39,000 participants in the UK Biobank, a new study shows.

An increase of 1 standard deviation in the sphericity index (short axis length/long axis length) was associated with a 47% increased incidence of cardiomyopathy and a 20% increased incidence of AFib, independent of clinical factors and traditional MRI measures.

Furthermore, a genetic analysis suggested a shared architecture between sphericity and nonischemic cardiomyopathy, pointing to NICM as a possible causal factor for left ventricle sphericity among individuals with normal LV size and function.

“Physicians have known the heart gets rounder after heart attacks and as we get older,” David Ouyang, MD, a cardiologist in the Smidt Heart Institute at Cedars-Sinai Medical Center, Los Angeles, and a researcher in the division of artificial intelligence in medicine, said in an interview. “We wanted to see if this sphericity is prognostic of future disease even in healthy individuals.”

Although it is too early to recommend heart shape assessment in healthy asymptomatic people, he said, “physicians should be extra careful and think about treatments when they notice a patient’s heart is particularly round.”

The study was published online March 29 in the journal Med.
 

Sphericity index key

The investigators hypothesized that there is variation in LV sphericity within the spectrum of normal LV chamber size and systolic function, and that such variation might be a marker of cardiac risk with genetic influences.

To test this hypothesis, they used automated deep-learning segmentation of cardiac MRI data to estimate and analyze the sphericity index in a cohort of 38,897 individuals participating in the UK Biobank.

After adjustment for age at MRI and sex, an increased sphericity index was associated with an increased risk for cardiomyopathy (hazard ratio, 1.57), AFib (HR, 1.35), and heart failure (HR, 1.37).

No significant association was seen with cardiac arrest.

The team then stratified the cohort into quintiles and compared the top 20%, middle 60%, and bottom 20%. The relationship between the sphericity index and risk extended across the distribution; individuals with higher than median sphericity had increased disease incidence, and those with lower than median sphericity had decreased incidence.

Overall, a single standard deviation in the sphericity index was associated with increased risk of cardiomyopathy (HR, 1.47) and of AFib (HR, 1.20), independent of clinical factors and usual MRI measurements.

In a minimally adjusted model, the sphericity index was a predictor of incident cardiomyopathy, AFib, and heart failure.

Adjustment for clinical factors partially attenuated the heart failure association; additional adjustment for MRI measurements fully attenuated that association and partially attenuated the association with AFib.

However, in all adjusted models, the association with cardiomyopathy showed little attenuation.

Furthermore, the team identified four loci associated with sphericity at genomewide significance – PLN, ANGPT1, PDZRN3, and HLA DR/DQ – and Mendelian randomization supported NICM as a cause of LV sphericity.
 

Looking ahead

“While conventional imaging metrics have significant diagnostic and prognostic value, some of these measurements have been adopted out of convenience or tradition,” the authors noted. “By representing a specific multidimensional remodeling phenotype, sphericity has emerged as a distinct morphologic trait with features not adequately captured by conventional measurements.

“We expect that the search space of potential imaging measurements is vast, and we have only begun to scratch at the surface of disease associations.”

Indeed, Dr. Ouyang said his group is “trying to evaluate the sphericity in echocardiograms or heart ultrasounds, which are more common and cheaper than MRI.”

“The main caveat is translating the information directly to patient care,” Richard C. Becker, MD, director and physician-in-chief of the University of Cincinnati Heart, Lung, and Vascular Institute, said in an interview. “Near-term yield could include using the spherical calculation in routine MRI of the heart, and based on the findings, following patients more closely if there is an abnormal shape. Or performing an MRI and targeted gene testing if there is a family history of cardiomyopathy or [of] an abnormal shape of the heart.”

“Validation of the findings and large-scale evaluation of the genes identified, and how they interact with patient and environmental factors, will be very important,” he added.

Nevertheless, “the study was well done and may serve as a foundation for future research,” Dr. Becker said. “The investigators used several powerful tools, including MRI, genomics, and [artificial intelligence] to draw their conclusions. This is precisely the way that ‘big data’ should be used – in a complementary fashion.”

The study authors and Dr. Becker reported no relevant financial relationships.

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

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

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

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

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

A high salt intake is an important risk factor for atherosclerosis, even in the absence of hypertension, a large study from Sweden concludes.

jirkaejc/Getty Images

The study, including more than 10,000 individuals between the ages of 50 and 64 years from the Swedish Cardiopulmonary bioImage Study, showed a significant link between dietary salt intake and the risk for atherosclerotic lesions in the coronary and carotid arteries, even in participants with normal blood pressure and without known cardiovascular disease.

The finding suggests that salt could be a damaging factor in its own right before the development of hypertension, the authors write. The results were published online in European Heart Journal Open.

It has been known for a long time that salt is linked to hypertension, but the role that salt plays in atherosclerosis has not been examined, first author Jonas Wuopio, MD, Karolinska Institutet, Huddinge, and Clinical Research Center, Falun, Uppsala University, both in Sweden, told this news organization.

“Hardly anyone looks at changes in the arteries’ calcification, the atherosclerotic plaques and the association with salt intake,” Dr. Wuopio said. “We had this exclusive data from our cohort, so we wanted to use it to close this knowledge gap.”

The analysis included 10,788 adults aged 50-64 years, (average age, 58 years; 52% women) who underwent a coronary computed tomography angiography (CCTA) scan. The estimated 24-hour sodium excretion was used to measure sodium intake.

CCTA was used to obtain 3-D images of the coronary arteries to measure the degree of coronary artery calcium as well as detect stenosis in the coronary arteries. Participants also had an ultrasound of the carotid arteries.

After adjusting for age, sex, and study site (the study was done at Uppsala and Malmö, Sweden), the researchers found that rising salt consumption was linked with increasing atherosclerosis in a linear fashion in both the coronary and carotid arteries.

Each 1,000 mg rise in sodium excretion was associated with a 9% increased occurrence of carotid plaque (odds ratio, 1.09; P < .001; confidence interval, 1.06-1.12), a higher coronary artery calcium score (OR, 1.16; P < .001; CI, 1.12-1.19), and a 17% increased occurrence of coronary artery stenosis (OR, 1.17; P < .001; CI, 1.13-1.20).

The association was abolished, though, after adjusting for blood pressure, they note. Their “interpretation is that the increase in blood pressure from sodium intake, even below the level that currently defines arterial hypertension, is an important factor that mediates the interplay between salt intake and the atherosclerotic process,” they write. “As we observed an association in individuals with normal blood pressure, one possible explanation for these findings is that the detrimental pathological processes begin already prior to the development of hypertension,” they note, although they caution that no causal relationships can be gleaned from this cross-sectional study.

They also reported no sign of a “J-curve”; participants with the lowest levels of sodium excretion had the lowest occurrence of both coronary and carotid atherosclerosis, which contradicts findings in some studies that found very low sodium linked to increased cardiovascular disease–related events.

“There have been some controversies among researchers regarding very low intake, where some say very low salt intake can increase the risk of cardiovascular disease, but we could not find this in this study,” Dr. Wuopio said.

“Our study is confirming that excess salt is not a good thing, but the fact that it is linked to atherosclerosis, even in the absence of hypertension, was a bit of a surprise,” he said.

“I will be telling my patients to follow the advice given by the World Health Organization and other medical societies, to limit your intake of salt to approximately 1 teaspoon, even if your blood pressure is normal.”


 

Time to scrutinize salt’s role in atherosclerosis

In an accompanying editorial, Maciej Banach, MD, Medical University of Lodz, and Stanislaw Surma, MD, Faculty of Medical Sciences in Katowice, both in Poland, write that excessive dietary salt intake is a well-documented cardiovascular risk factor, and that the association is explained in most studies by increased blood pressure.

“We should look more extensively on the role of dietary salt, as it affects many pathological mechanisms, by which, especially with the coexistence of other risk factors, atherosclerosis may progress very fast,” they write.

“The results of the study shed new light on the direct relationship between excessive dietary salt intake and the risk of ASCVD [atherosclerotic cardiovascular disease], indicating that salt intake might be a risk factor for atherosclerosis even prior to the development of hypertension,” they conclude.
 

Confirmatory and novel

“Nobody questions the fact that high blood pressure is a powerful risk factor for atherosclerotic disease, but not all studies have suggested that, at least at significantly higher levels of sodium intake, that high salt intake tracks with risk for atherosclerotic disease,” Alon Gitig, MD, assistant professor and director of cardiology, Mount Sinai Doctors-Westchester, Yonkers, New York, told this news organization.

Most of the studies of salt intake in the diet are based on patient self-reports via food frequency questionnaires, which can give a general idea of salt intake, but are often not totally accurate, Dr. Gitig said.

“Here, they measured sodium in the urine and estimated the 24-hour salt intake from that, which is slightly novel,” he said.

Everybody knows that high blood pressure is associated with future cardiovascular disease risk, but what many don’t realize is that that risk starts to increase slightly but significantly above a blood pressure that is already in the range of 115 mm Hg/75 mm Hg, he said.

“The lower you can get your blood pressure down, to around 115-120, the lower your risk for cardiovascular disease,” Dr. Gitig said.

It is possible for most people to lower blood pressure through attention to diet, restricting sodium, performing cardio and weight training exercises, and maintaining a healthy weight, he said.

An example of a cardiovascular health diet is the Dietary Approaches to Stop Hypertension (DASH) diet.

“The DASH diet, consisting of 9 servings of fruits and vegetables a day with few refined carbs, flour and sugar, has been shown in a randomized trial to dramatically reduce blood pressure. There are two reasons for that. One is that the fruits and vegetables have many phytonutrients that are good for arteries. The other is that a large proportion of U.S. adults have insulin resistance, which leads to high blood pressure.  

“The more fruits and vegetables and healthy animal products, and less sugar and flour, the more you are going to improve your insulin resistance, so you can bring your blood pressure down that way,” Dr. Gitig said.

The study was funded by the Swedish Heart-Lung Foundation, the Knut and Alice Wallenberg Foundation, the Swedish Research Council and Vinnova (Sweden’s Innovation agency), the University of Gothenburg and Sahlgrenska University Hospital, the Karolinska Institutet and Stockholm County Council, the Linköping University and University Hospital, the Lund University and Skane University Hospital, the Umea University and University Hospital, and the Uppsala University and University Hospital. Dr. Wuopio and Dr. Gitig report no relevant financial relationships. Dr. Banach reports financial relationships with Adamed, Amgen, Daichii Sankyo, Esperion, KrKa, NewAmsterdam, Polpharma, Novartis, Pfizer, Sanofi, Teva, Viatris, and CMDO at Longevity Group (LU). Dr. Surma reports a financial relationship with Sanofi and Novartis.

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

An updated consensus statement on transcatheter left atrial appendage closure (LAAC) has put a newfound focus on patient selection for the procedure, specifically recommending that the procedure is appropriate for patients with nonvalvular atrial fibrillation who have risk for thromboembolism, aren’t well suited for direct oral anticoagulants (DOACs) and have a good chance of living for at least another year.

The statement, published online in the Journal of the Society for Cardiovascular Angiography & Interventions, also makes recommendations for how much experience operators should have, how many procedures they should perform to keep their skills up, and when and how to use imaging and prescribe DOACs, among other suggestions.

The statement represents the first updated guidance for LAAC since 2015. “Since then this field has really expanded and evolved,” writing group chair Jacqueline Saw, MD, said in an interview. “For instance, the indications are more matured and specific, and the procedural technical steps have matured. Imaging has also advanced, there’s more understanding about postprocedural care and there are also new devices that have been approved.”

Dr. Saw, an interventional cardiologist at Vancouver General Hospital and St. Paul’s Hospital, and a professor at the University of British Columbia in Vancouver, called the statement “a piece that puts everything together.”

“This document really summarizes the whole practice for doing transcatheter procedures,” she added, “so it’s all-in-one document in terms of recommendation of who we do the procedure for, how we should do it, how we should image and guide the procedure, and what complications to look out for and how to manage patients post procedure, be it with antithrombotic therapy and/or device surveillance.”

 13 recommendations

In all, the statement carries 13 recommendations for LAAC. The Society for Cardiovascular Angiography & Interventions and the Heart Rhythm Society commissioned the writing group. The American College of Cardiology and Society of Cardiovascular Computed Tomography have endorsed the statement. The following are among the recommendations:

• Transcatheter LAAC is appropriate for patients with nonvalvular atrial fibrillation with high thromboembolic risk but for whom long-term oral anticoagulation may be contraindicated and who have at least 1 year’s life expectancy.
• Operators should have performed at least 50 prior left-sided ablations or structural procedures and at least 25 transseptal punctures (TSPs). Interventional-imaging physicians should have experience in guiding 25 or more TSPs before supporting LAAC procedures independently.
• To maintain skills, operators should do 25 or more TSPs and at least 12 LAACs over each 2-year period.
• On-site cardiovascular surgery backup should be available for new programs and for operators early in their learning curve.
• Baseline imaging with transesophageal echocardiography (TEE) or cardiac computed tomography should be performed before LAAC.
• Intraprocedural imaging guidance with TEE or intracardiac echocardiography.
• Follow labeling of each specific LAAC device for technical aspects of the procedure.
• Familiarity with avoiding, recognizing, and managing LAAC complications.
• Predischarge 2-dimensional TEE to rule out pericardial effusion and device embolization.
• Anticoagulation for device-related thrombus.
• Make all efforts to minimize peridevice leaks during implantation because their clinical impact and management isn’t well understood.
• Antithrombotic therapy with warfarin, DOAC, or dual-antiplatelet therapy after LAAC based on the studied regimen and instructions for each specific device, tailored to the bleeding risks for each patient.
• TEE or cardiac computed tomography at 45-90 days after LAAC for device surveillance to assess for peridevice leak and device-related thrombus.

The statement also includes precautionary recommendations. It advises against using routine closure of LAAC-associated iatrogenic atrial septal defects and states that combined procedures with LAAC, such as structural interventions and pulmonary vein isolation, should be avoided because randomized controlled trial data are pending.

“These recommendations are based upon data from updated publications and randomized trial data as well as large registries, including the National Cardiovascular Data Registry, so I think this is a very practical statement that puts all these pieces together for any budding interventionalist doing this procedure and even experienced operations,” Dr. Saw said.

Authors of an accompanying editorial agreed that the “rigorous standards” set out in the statement will help maintain “a high level of procedural safety in the setting of rapid expansion.”

The editorialists, Faisal M. Merchant, MD, of Emory University, Atlanta, and Mohamad Alkhouli, MD, professor of medicine at Mayo Clinic School of Medicine, Rochester, Minn., point out that the incidence of pericardial effusion has decreased from more than 5% in the pivotal Watchman trials to less than 1.5% in the most recent report from the National Cardiovascular Data Registry, which shows that more than 100,000 procedures have been performed in the United States.

But most important as the field moves forward, they stress, is patient selection. The recommendation of limiting patients to those with a life expectancy of 1 year “is a tacit recognition of the fact that the benefits of LAAC take time to accrue, and many older and frail patients are unlikely to derive meaningful benefit.”

Dr. Merchant and Dr. Alkhouli also note that there remains a conundrum in patient selection that remains from the original LAAC trials, which enrolled patients who were eligible for anticoagulation. “Somewhat paradoxically, after its approval, LAAC is mostly prescribed to patients who are not felt to be good anticoagulation candidates.” This leaves physicians “in the precarious position of extrapolating data to patients who were excluded from the original clinical trials.”

Therefore, the consensus statement “is right to put patient selection front and center in its recommendations, but as the field of LAAC comes of age, better evidence to support patient selection will be the real sign of maturity.”

Dr. Saw said she envisions another update over the next 2 years or so as ongoing clinical trials comparing DOAC and LAAC, namely the CHAMPION-AF and OPTION trials, report results.

Dr. Saw and Dr. Merchant, reported no conflicts of interest. Dr. Alkhouli has financial ties to Boston Scientific, Abbott, and Philips.

An updated consensus statement on transcatheter left atrial appendage closure (LAAC) has put a newfound focus on patient selection for the procedure, specifically recommending that the procedure is appropriate for patients with nonvalvular atrial fibrillation who have risk for thromboembolism, aren’t well suited for direct oral anticoagulants (DOACs) and have a good chance of living for at least another year.

The statement, published online in the Journal of the Society for Cardiovascular Angiography & Interventions, also makes recommendations for how much experience operators should have, how many procedures they should perform to keep their skills up, and when and how to use imaging and prescribe DOACs, among other suggestions.

The statement represents the first updated guidance for LAAC since 2015. “Since then this field has really expanded and evolved,” writing group chair Jacqueline Saw, MD, said in an interview. “For instance, the indications are more matured and specific, and the procedural technical steps have matured. Imaging has also advanced, there’s more understanding about postprocedural care and there are also new devices that have been approved.”

Dr. Saw, an interventional cardiologist at Vancouver General Hospital and St. Paul’s Hospital, and a professor at the University of British Columbia in Vancouver, called the statement “a piece that puts everything together.”

“This document really summarizes the whole practice for doing transcatheter procedures,” she added, “so it’s all-in-one document in terms of recommendation of who we do the procedure for, how we should do it, how we should image and guide the procedure, and what complications to look out for and how to manage patients post procedure, be it with antithrombotic therapy and/or device surveillance.”

 13 recommendations

In all, the statement carries 13 recommendations for LAAC. The Society for Cardiovascular Angiography & Interventions and the Heart Rhythm Society commissioned the writing group. The American College of Cardiology and Society of Cardiovascular Computed Tomography have endorsed the statement. The following are among the recommendations:

• Transcatheter LAAC is appropriate for patients with nonvalvular atrial fibrillation with high thromboembolic risk but for whom long-term oral anticoagulation may be contraindicated and who have at least 1 year’s life expectancy.
• Operators should have performed at least 50 prior left-sided ablations or structural procedures and at least 25 transseptal punctures (TSPs). Interventional-imaging physicians should have experience in guiding 25 or more TSPs before supporting LAAC procedures independently.
• To maintain skills, operators should do 25 or more TSPs and at least 12 LAACs over each 2-year period.
• On-site cardiovascular surgery backup should be available for new programs and for operators early in their learning curve.
• Baseline imaging with transesophageal echocardiography (TEE) or cardiac computed tomography should be performed before LAAC.
• Intraprocedural imaging guidance with TEE or intracardiac echocardiography.
• Follow labeling of each specific LAAC device for technical aspects of the procedure.
• Familiarity with avoiding, recognizing, and managing LAAC complications.
• Predischarge 2-dimensional TEE to rule out pericardial effusion and device embolization.
• Anticoagulation for device-related thrombus.
• Make all efforts to minimize peridevice leaks during implantation because their clinical impact and management isn’t well understood.
• Antithrombotic therapy with warfarin, DOAC, or dual-antiplatelet therapy after LAAC based on the studied regimen and instructions for each specific device, tailored to the bleeding risks for each patient.
• TEE or cardiac computed tomography at 45-90 days after LAAC for device surveillance to assess for peridevice leak and device-related thrombus.

The statement also includes precautionary recommendations. It advises against using routine closure of LAAC-associated iatrogenic atrial septal defects and states that combined procedures with LAAC, such as structural interventions and pulmonary vein isolation, should be avoided because randomized controlled trial data are pending.

“These recommendations are based upon data from updated publications and randomized trial data as well as large registries, including the National Cardiovascular Data Registry, so I think this is a very practical statement that puts all these pieces together for any budding interventionalist doing this procedure and even experienced operations,” Dr. Saw said.

Authors of an accompanying editorial agreed that the “rigorous standards” set out in the statement will help maintain “a high level of procedural safety in the setting of rapid expansion.”

The editorialists, Faisal M. Merchant, MD, of Emory University, Atlanta, and Mohamad Alkhouli, MD, professor of medicine at Mayo Clinic School of Medicine, Rochester, Minn., point out that the incidence of pericardial effusion has decreased from more than 5% in the pivotal Watchman trials to less than 1.5% in the most recent report from the National Cardiovascular Data Registry, which shows that more than 100,000 procedures have been performed in the United States.

But most important as the field moves forward, they stress, is patient selection. The recommendation of limiting patients to those with a life expectancy of 1 year “is a tacit recognition of the fact that the benefits of LAAC take time to accrue, and many older and frail patients are unlikely to derive meaningful benefit.”

Dr. Merchant and Dr. Alkhouli also note that there remains a conundrum in patient selection that remains from the original LAAC trials, which enrolled patients who were eligible for anticoagulation. “Somewhat paradoxically, after its approval, LAAC is mostly prescribed to patients who are not felt to be good anticoagulation candidates.” This leaves physicians “in the precarious position of extrapolating data to patients who were excluded from the original clinical trials.”

Therefore, the consensus statement “is right to put patient selection front and center in its recommendations, but as the field of LAAC comes of age, better evidence to support patient selection will be the real sign of maturity.”

Dr. Saw said she envisions another update over the next 2 years or so as ongoing clinical trials comparing DOAC and LAAC, namely the CHAMPION-AF and OPTION trials, report results.

Dr. Saw and Dr. Merchant, reported no conflicts of interest. Dr. Alkhouli has financial ties to Boston Scientific, Abbott, and Philips.

An updated consensus statement on transcatheter left atrial appendage closure (LAAC) has put a newfound focus on patient selection for the procedure, specifically recommending that the procedure is appropriate for patients with nonvalvular atrial fibrillation who have risk for thromboembolism, aren’t well suited for direct oral anticoagulants (DOACs) and have a good chance of living for at least another year.

The statement, published online in the Journal of the Society for Cardiovascular Angiography & Interventions, also makes recommendations for how much experience operators should have, how many procedures they should perform to keep their skills up, and when and how to use imaging and prescribe DOACs, among other suggestions.

The statement represents the first updated guidance for LAAC since 2015. “Since then this field has really expanded and evolved,” writing group chair Jacqueline Saw, MD, said in an interview. “For instance, the indications are more matured and specific, and the procedural technical steps have matured. Imaging has also advanced, there’s more understanding about postprocedural care and there are also new devices that have been approved.”

Dr. Saw, an interventional cardiologist at Vancouver General Hospital and St. Paul’s Hospital, and a professor at the University of British Columbia in Vancouver, called the statement “a piece that puts everything together.”

“This document really summarizes the whole practice for doing transcatheter procedures,” she added, “so it’s all-in-one document in terms of recommendation of who we do the procedure for, how we should do it, how we should image and guide the procedure, and what complications to look out for and how to manage patients post procedure, be it with antithrombotic therapy and/or device surveillance.”

 13 recommendations

In all, the statement carries 13 recommendations for LAAC. The Society for Cardiovascular Angiography & Interventions and the Heart Rhythm Society commissioned the writing group. The American College of Cardiology and Society of Cardiovascular Computed Tomography have endorsed the statement. The following are among the recommendations:

• Transcatheter LAAC is appropriate for patients with nonvalvular atrial fibrillation with high thromboembolic risk but for whom long-term oral anticoagulation may be contraindicated and who have at least 1 year’s life expectancy.
• Operators should have performed at least 50 prior left-sided ablations or structural procedures and at least 25 transseptal punctures (TSPs). Interventional-imaging physicians should have experience in guiding 25 or more TSPs before supporting LAAC procedures independently.
• To maintain skills, operators should do 25 or more TSPs and at least 12 LAACs over each 2-year period.
• On-site cardiovascular surgery backup should be available for new programs and for operators early in their learning curve.
• Baseline imaging with transesophageal echocardiography (TEE) or cardiac computed tomography should be performed before LAAC.
• Intraprocedural imaging guidance with TEE or intracardiac echocardiography.
• Follow labeling of each specific LAAC device for technical aspects of the procedure.
• Familiarity with avoiding, recognizing, and managing LAAC complications.
• Predischarge 2-dimensional TEE to rule out pericardial effusion and device embolization.
• Anticoagulation for device-related thrombus.
• Make all efforts to minimize peridevice leaks during implantation because their clinical impact and management isn’t well understood.
• Antithrombotic therapy with warfarin, DOAC, or dual-antiplatelet therapy after LAAC based on the studied regimen and instructions for each specific device, tailored to the bleeding risks for each patient.
• TEE or cardiac computed tomography at 45-90 days after LAAC for device surveillance to assess for peridevice leak and device-related thrombus.

The statement also includes precautionary recommendations. It advises against using routine closure of LAAC-associated iatrogenic atrial septal defects and states that combined procedures with LAAC, such as structural interventions and pulmonary vein isolation, should be avoided because randomized controlled trial data are pending.

“These recommendations are based upon data from updated publications and randomized trial data as well as large registries, including the National Cardiovascular Data Registry, so I think this is a very practical statement that puts all these pieces together for any budding interventionalist doing this procedure and even experienced operations,” Dr. Saw said.

Authors of an accompanying editorial agreed that the “rigorous standards” set out in the statement will help maintain “a high level of procedural safety in the setting of rapid expansion.”

The editorialists, Faisal M. Merchant, MD, of Emory University, Atlanta, and Mohamad Alkhouli, MD, professor of medicine at Mayo Clinic School of Medicine, Rochester, Minn., point out that the incidence of pericardial effusion has decreased from more than 5% in the pivotal Watchman trials to less than 1.5% in the most recent report from the National Cardiovascular Data Registry, which shows that more than 100,000 procedures have been performed in the United States.

But most important as the field moves forward, they stress, is patient selection. The recommendation of limiting patients to those with a life expectancy of 1 year “is a tacit recognition of the fact that the benefits of LAAC take time to accrue, and many older and frail patients are unlikely to derive meaningful benefit.”

Dr. Merchant and Dr. Alkhouli also note that there remains a conundrum in patient selection that remains from the original LAAC trials, which enrolled patients who were eligible for anticoagulation. “Somewhat paradoxically, after its approval, LAAC is mostly prescribed to patients who are not felt to be good anticoagulation candidates.” This leaves physicians “in the precarious position of extrapolating data to patients who were excluded from the original clinical trials.”

Therefore, the consensus statement “is right to put patient selection front and center in its recommendations, but as the field of LAAC comes of age, better evidence to support patient selection will be the real sign of maturity.”

Dr. Saw said she envisions another update over the next 2 years or so as ongoing clinical trials comparing DOAC and LAAC, namely the CHAMPION-AF and OPTION trials, report results.

Dr. Saw and Dr. Merchant, reported no conflicts of interest. Dr. Alkhouli has financial ties to Boston Scientific, Abbott, and Philips.

It remained an open question in 2018, on the unveiling of the COAPT trial’s 2-year primary results, whether the striking reductions in mortality and heart-failure (HF) hospitalization observed for transcatheter edge-to-edge repair (TEER) with the MitraClip (Abbott) would be durable with longer follow-up.

The trial had enrolled an especially sick population of symptomatic patients with mitral regurgitation (MR) secondary to HF.

As it turns out, the therapy’s benefits at 2 years were indeed durable, at least out to 5 years, investigators reported March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The results were simultaneously published in the New England Journal of Medicine.

Patients who received the MitraClip on top of intensive medical therapy, compared with a group assigned to medical management alone, benefited significantly at 5 years with risk reductions of 51% for HF hospitalization, 28% for death from any cause, and 47% for the composite of the two events.

Still, mortality at 5 years among the 614 randomized patients was steep at 57.3% in the MitraClip group and 67.2% for those assigned to meds only, underscoring the need for early identification of patients appropriate for the device therapy, Gregg W. Stone, MD, said during his presentation.

Dr. Stone, of the Icahn School of Medicine at Mount Sinai, New York, is a COAPT co-principal investigator and lead author of the 5-year outcomes publication.

Exclusions based on LV dimension

The COAPT trial included 614 patients with HF and symptomatic MR despite guideline-directed medical therapy. They were required to have moderate to severe (3+) or severe (4+) MR confirmed by an echocardiographic core laboratory and a left ventricular ejection fraction (LVEF) of 20%-50%.

Among the exclusion criteria were an LV end-systolic diameter greater than 70 mm, severe pulmonary hypertension, and moderate to severe symptomatic right ventricular failure.

The systolic LV dimension exclusion helped address the persistent question of whether “severe mitral regurgitation is a marker of a bad left ventricle or ... contributes to the pathophysiology” of MR and its poor outcomes, Dr. Stone said.

The 51% reduction in risk for time-to-first HF hospitalization among patients assigned to TEER “accrued very early,” Dr. Stone pointed out. “You can see the curves start to separate almost immediately after you reduce left atrial pressure and volume overload with the MitraClip.”

The curves stopped diverging after about 3 years because of crossover from the control group, he said. Still, “we had shown a substantial absolute 17% reduction in mortality at 2 years” with MitraClip. “That has continued out to 5 years, with a statistically significant 28% relative reduction,” he continued, and the absolute risk reduction reaching 10%.

Patients in the control group who crossed over “basically assumed the death and heart failure hospitalization rate of the MitraClip group,” Dr. Stone said. That wasn’t surprising “because most of the patients enrolled in the trial originally had chronic heart failure.” It’s “confirmation of the principal results of the trial.”
 

Comparison With MITRA-FR

“We know that MITRA-FR was a negative trial,” observed Wayne B. Batchelor, MD, an invited discussant following Dr. Stone’s presentation, referring to an earlier similar trial that showed no advantage for MitraClip. Compared with MITRA-FR, COAPT “has created an entirely different story.”

The marked reductions in mortality and risk for adverse events and low number-needed-to-treat with MitraClip are “really remarkable,” said Dr. Batchelor, who is with the Inova Heart and Vascular Institute, Falls Church, Va.

But the high absolute mortality for patients in the COAPT control group “speaks volumes to me and tells us that we’ve got to identify our patients well early,” he agreed, and to “implement transcatheter edge-to-edge therapy in properly selected patients on guideline-directed medical therapy in order to avoid that.”

The trial findings “suggest that we’re reducing HF hospitalization,” he said, “so this is an extremely potent therapy, potentially.

“The dramatic difference between the treated arm and the medical therapy arm in this trial makes me feel that this therapy is here to stay,” Dr. Batchelor concluded. “We just have to figure out how to deploy it properly in the right patients.”

The COAPT trial presents “a practice-changing paradigm,” said Suzanne J. Baron, MD, of Lahey Hospital & Medical Center, Burlington, Mass., another invited discussant.

The crossover data “really jumped out,” she added. “Waiting to treat patients with TEER may be harmful, so if we’re going to consider treating earlier, how do we identify the right patient?” Dr. Baron asked, especially given the negative MITRA-FR results.

MITRA-FR didn’t follow patients beyond 2 years, Dr. Stone noted. Still, “we do think that the main difference was that COAPT enrolled a patient population with more severe MR and slightly less LV dysfunction, at least in terms of the LV not being as dilated, so they didn’t have end-stage LV disease. Whereas in MITRA-FR, more of the patients had only moderate mitral regurgitation.” And big dilated left ventricles “are less likely to benefit.”

There were also differences between the studies in technique and background medical therapies, he added.

The Food and Drug Administration has approved – and payers are paying – for the treatment of patients who meet the COAPT criteria, “in whom we can be very confident they have a benefit,” Dr. Stone said.

“The real question is: Where are the edges where we should consider this? LVEF slightly less than 20% or slightly greater than 50%? Or primary atrial functional mitral regurgitation? There are registry data to suggest that they would benefit,” he said, but “we need more data.”

COAPT was supported by Abbott. Dr. Stone disclosed receiving speaker honoraria from Abbott and consulting fees or equity from Neovasc, Ancora, Valfix, and Cardiac Success; and that Mount Sinai receives research funding from Abbott. Disclosures for the other authors are available at nejm.org. Dr. Batchelor has disclosed receiving consultant fees or honoraria from Abbott, Boston Scientific, Idorsia, and V-Wave Medical, and having other ties with Medtronic. Dr. Baron has disclosed receiving consultant fees or honoraria from Abiomed, Biotronik, Boston Scientific, Edwards Lifesciences, Medtronic, Shockwave, and Zoll Medical, and conducting research or receiving research grants from Abiomed and Boston Scientific.
 

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

It remained an open question in 2018, on the unveiling of the COAPT trial’s 2-year primary results, whether the striking reductions in mortality and heart-failure (HF) hospitalization observed for transcatheter edge-to-edge repair (TEER) with the MitraClip (Abbott) would be durable with longer follow-up.

The trial had enrolled an especially sick population of symptomatic patients with mitral regurgitation (MR) secondary to HF.

As it turns out, the therapy’s benefits at 2 years were indeed durable, at least out to 5 years, investigators reported March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The results were simultaneously published in the New England Journal of Medicine.

Patients who received the MitraClip on top of intensive medical therapy, compared with a group assigned to medical management alone, benefited significantly at 5 years with risk reductions of 51% for HF hospitalization, 28% for death from any cause, and 47% for the composite of the two events.

Still, mortality at 5 years among the 614 randomized patients was steep at 57.3% in the MitraClip group and 67.2% for those assigned to meds only, underscoring the need for early identification of patients appropriate for the device therapy, Gregg W. Stone, MD, said during his presentation.

Dr. Stone, of the Icahn School of Medicine at Mount Sinai, New York, is a COAPT co-principal investigator and lead author of the 5-year outcomes publication.

Exclusions based on LV dimension

The COAPT trial included 614 patients with HF and symptomatic MR despite guideline-directed medical therapy. They were required to have moderate to severe (3+) or severe (4+) MR confirmed by an echocardiographic core laboratory and a left ventricular ejection fraction (LVEF) of 20%-50%.

Among the exclusion criteria were an LV end-systolic diameter greater than 70 mm, severe pulmonary hypertension, and moderate to severe symptomatic right ventricular failure.

The systolic LV dimension exclusion helped address the persistent question of whether “severe mitral regurgitation is a marker of a bad left ventricle or ... contributes to the pathophysiology” of MR and its poor outcomes, Dr. Stone said.

The 51% reduction in risk for time-to-first HF hospitalization among patients assigned to TEER “accrued very early,” Dr. Stone pointed out. “You can see the curves start to separate almost immediately after you reduce left atrial pressure and volume overload with the MitraClip.”

The curves stopped diverging after about 3 years because of crossover from the control group, he said. Still, “we had shown a substantial absolute 17% reduction in mortality at 2 years” with MitraClip. “That has continued out to 5 years, with a statistically significant 28% relative reduction,” he continued, and the absolute risk reduction reaching 10%.

Patients in the control group who crossed over “basically assumed the death and heart failure hospitalization rate of the MitraClip group,” Dr. Stone said. That wasn’t surprising “because most of the patients enrolled in the trial originally had chronic heart failure.” It’s “confirmation of the principal results of the trial.”
 

Comparison With MITRA-FR

“We know that MITRA-FR was a negative trial,” observed Wayne B. Batchelor, MD, an invited discussant following Dr. Stone’s presentation, referring to an earlier similar trial that showed no advantage for MitraClip. Compared with MITRA-FR, COAPT “has created an entirely different story.”

The marked reductions in mortality and risk for adverse events and low number-needed-to-treat with MitraClip are “really remarkable,” said Dr. Batchelor, who is with the Inova Heart and Vascular Institute, Falls Church, Va.

But the high absolute mortality for patients in the COAPT control group “speaks volumes to me and tells us that we’ve got to identify our patients well early,” he agreed, and to “implement transcatheter edge-to-edge therapy in properly selected patients on guideline-directed medical therapy in order to avoid that.”

The trial findings “suggest that we’re reducing HF hospitalization,” he said, “so this is an extremely potent therapy, potentially.

“The dramatic difference between the treated arm and the medical therapy arm in this trial makes me feel that this therapy is here to stay,” Dr. Batchelor concluded. “We just have to figure out how to deploy it properly in the right patients.”

The COAPT trial presents “a practice-changing paradigm,” said Suzanne J. Baron, MD, of Lahey Hospital & Medical Center, Burlington, Mass., another invited discussant.

The crossover data “really jumped out,” she added. “Waiting to treat patients with TEER may be harmful, so if we’re going to consider treating earlier, how do we identify the right patient?” Dr. Baron asked, especially given the negative MITRA-FR results.

MITRA-FR didn’t follow patients beyond 2 years, Dr. Stone noted. Still, “we do think that the main difference was that COAPT enrolled a patient population with more severe MR and slightly less LV dysfunction, at least in terms of the LV not being as dilated, so they didn’t have end-stage LV disease. Whereas in MITRA-FR, more of the patients had only moderate mitral regurgitation.” And big dilated left ventricles “are less likely to benefit.”

There were also differences between the studies in technique and background medical therapies, he added.

The Food and Drug Administration has approved – and payers are paying – for the treatment of patients who meet the COAPT criteria, “in whom we can be very confident they have a benefit,” Dr. Stone said.

“The real question is: Where are the edges where we should consider this? LVEF slightly less than 20% or slightly greater than 50%? Or primary atrial functional mitral regurgitation? There are registry data to suggest that they would benefit,” he said, but “we need more data.”

COAPT was supported by Abbott. Dr. Stone disclosed receiving speaker honoraria from Abbott and consulting fees or equity from Neovasc, Ancora, Valfix, and Cardiac Success; and that Mount Sinai receives research funding from Abbott. Disclosures for the other authors are available at nejm.org. Dr. Batchelor has disclosed receiving consultant fees or honoraria from Abbott, Boston Scientific, Idorsia, and V-Wave Medical, and having other ties with Medtronic. Dr. Baron has disclosed receiving consultant fees or honoraria from Abiomed, Biotronik, Boston Scientific, Edwards Lifesciences, Medtronic, Shockwave, and Zoll Medical, and conducting research or receiving research grants from Abiomed and Boston Scientific.
 

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

It remained an open question in 2018, on the unveiling of the COAPT trial’s 2-year primary results, whether the striking reductions in mortality and heart-failure (HF) hospitalization observed for transcatheter edge-to-edge repair (TEER) with the MitraClip (Abbott) would be durable with longer follow-up.

The trial had enrolled an especially sick population of symptomatic patients with mitral regurgitation (MR) secondary to HF.

As it turns out, the therapy’s benefits at 2 years were indeed durable, at least out to 5 years, investigators reported March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. The results were simultaneously published in the New England Journal of Medicine.

Patients who received the MitraClip on top of intensive medical therapy, compared with a group assigned to medical management alone, benefited significantly at 5 years with risk reductions of 51% for HF hospitalization, 28% for death from any cause, and 47% for the composite of the two events.

Still, mortality at 5 years among the 614 randomized patients was steep at 57.3% in the MitraClip group and 67.2% for those assigned to meds only, underscoring the need for early identification of patients appropriate for the device therapy, Gregg W. Stone, MD, said during his presentation.

Dr. Stone, of the Icahn School of Medicine at Mount Sinai, New York, is a COAPT co-principal investigator and lead author of the 5-year outcomes publication.

Exclusions based on LV dimension

The COAPT trial included 614 patients with HF and symptomatic MR despite guideline-directed medical therapy. They were required to have moderate to severe (3+) or severe (4+) MR confirmed by an echocardiographic core laboratory and a left ventricular ejection fraction (LVEF) of 20%-50%.

Among the exclusion criteria were an LV end-systolic diameter greater than 70 mm, severe pulmonary hypertension, and moderate to severe symptomatic right ventricular failure.

The systolic LV dimension exclusion helped address the persistent question of whether “severe mitral regurgitation is a marker of a bad left ventricle or ... contributes to the pathophysiology” of MR and its poor outcomes, Dr. Stone said.

The 51% reduction in risk for time-to-first HF hospitalization among patients assigned to TEER “accrued very early,” Dr. Stone pointed out. “You can see the curves start to separate almost immediately after you reduce left atrial pressure and volume overload with the MitraClip.”

The curves stopped diverging after about 3 years because of crossover from the control group, he said. Still, “we had shown a substantial absolute 17% reduction in mortality at 2 years” with MitraClip. “That has continued out to 5 years, with a statistically significant 28% relative reduction,” he continued, and the absolute risk reduction reaching 10%.

Patients in the control group who crossed over “basically assumed the death and heart failure hospitalization rate of the MitraClip group,” Dr. Stone said. That wasn’t surprising “because most of the patients enrolled in the trial originally had chronic heart failure.” It’s “confirmation of the principal results of the trial.”
 

Comparison With MITRA-FR

“We know that MITRA-FR was a negative trial,” observed Wayne B. Batchelor, MD, an invited discussant following Dr. Stone’s presentation, referring to an earlier similar trial that showed no advantage for MitraClip. Compared with MITRA-FR, COAPT “has created an entirely different story.”

The marked reductions in mortality and risk for adverse events and low number-needed-to-treat with MitraClip are “really remarkable,” said Dr. Batchelor, who is with the Inova Heart and Vascular Institute, Falls Church, Va.

But the high absolute mortality for patients in the COAPT control group “speaks volumes to me and tells us that we’ve got to identify our patients well early,” he agreed, and to “implement transcatheter edge-to-edge therapy in properly selected patients on guideline-directed medical therapy in order to avoid that.”

The trial findings “suggest that we’re reducing HF hospitalization,” he said, “so this is an extremely potent therapy, potentially.

“The dramatic difference between the treated arm and the medical therapy arm in this trial makes me feel that this therapy is here to stay,” Dr. Batchelor concluded. “We just have to figure out how to deploy it properly in the right patients.”

The COAPT trial presents “a practice-changing paradigm,” said Suzanne J. Baron, MD, of Lahey Hospital & Medical Center, Burlington, Mass., another invited discussant.

The crossover data “really jumped out,” she added. “Waiting to treat patients with TEER may be harmful, so if we’re going to consider treating earlier, how do we identify the right patient?” Dr. Baron asked, especially given the negative MITRA-FR results.

MITRA-FR didn’t follow patients beyond 2 years, Dr. Stone noted. Still, “we do think that the main difference was that COAPT enrolled a patient population with more severe MR and slightly less LV dysfunction, at least in terms of the LV not being as dilated, so they didn’t have end-stage LV disease. Whereas in MITRA-FR, more of the patients had only moderate mitral regurgitation.” And big dilated left ventricles “are less likely to benefit.”

There were also differences between the studies in technique and background medical therapies, he added.

The Food and Drug Administration has approved – and payers are paying – for the treatment of patients who meet the COAPT criteria, “in whom we can be very confident they have a benefit,” Dr. Stone said.

“The real question is: Where are the edges where we should consider this? LVEF slightly less than 20% or slightly greater than 50%? Or primary atrial functional mitral regurgitation? There are registry data to suggest that they would benefit,” he said, but “we need more data.”

COAPT was supported by Abbott. Dr. Stone disclosed receiving speaker honoraria from Abbott and consulting fees or equity from Neovasc, Ancora, Valfix, and Cardiac Success; and that Mount Sinai receives research funding from Abbott. Disclosures for the other authors are available at nejm.org. Dr. Batchelor has disclosed receiving consultant fees or honoraria from Abbott, Boston Scientific, Idorsia, and V-Wave Medical, and having other ties with Medtronic. Dr. Baron has disclosed receiving consultant fees or honoraria from Abiomed, Biotronik, Boston Scientific, Edwards Lifesciences, Medtronic, Shockwave, and Zoll Medical, and conducting research or receiving research grants from Abiomed and Boston Scientific.
 

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

The relatively recent innovation of heart transplantation after circulatory death of the donor is increasing the number of donor hearts available and leading to many more lives on the heart transplant waiting list being saved. Experts agree it’s a major and very welcome advance in medicine.

However, some of the processes involved in one approach to donation after circulatory death has raised ethical concerns and questions about whether they violate the “dead donor rule” – a principle that requires patients be declared dead before removal of life-sustaining organs for transplant.  

Rasi Bhadramani/iStock/Getty Images

Experts in the fields of transplantation and medical ethics have yet to reach consensus, causing problems for the transplant community, who worry that this could cause a loss of confidence in the entire transplant process.
 

A new pathway for heart transplantation

The traditional approach to transplantation is to retrieve organs from a donor who has been declared brain dead, known as “donation after brain death (DBD).” These patients have usually suffered a catastrophic brain injury but survived to get to intensive care.

As the brain swells because of injury, it becomes evident that all brain function is lost, and the patient is declared brain dead. However, breathing is maintained by the ventilator and the heart is still beating. Because the organs are being oxygenated, there is no immediate rush to retrieve the organs and the heart can be evaluated for its suitability for transplant in a calm and methodical way before it is removed.  

However, there is a massive shortage of organs, especially hearts, partially because of the limited number of donors who are declared brain dead in that setting.

In recent years, another pathway for organ transplantation has become available: “donation after circulatory death (DCD).” These patients also have suffered a catastrophic brain injury considered to be nonsurvivable, but unlike the DBD situation, the brain still has some function, so the patient does not meet the criteria for brain death. 

Still, because the patient is considered to have no chance of a meaningful recovery, the family often recognizes the futility of treatment and agrees to the withdrawal of life support. When this happens, the heart normally stops beating after a period of time. There is then a “stand-off time” – normally 5 minutes – after which death is declared and the organs can be removed. 

The difficulty with this approach, however, is that because the heart has been stopped, it has been deprived of oxygen, potentially causing injury. While DCD has been practiced for several years to retrieve organs such as the kidney, liver, lungs, and pancreas, the heart is more difficult as it is more susceptible to oxygen deprivation. And for the heart to be assessed for transplant suitability, it should ideally be beating, so it has to be reperfused and restarted quickly after death has been declared.

For many years it was thought the oxygen deprivation that occurs after circulatory death would be too much to provide a functional organ. But researchers in the United Kingdom and Australia developed techniques to overcome this problem, and early DCD heart transplants took place in 2014 in Australia, and in 2015 in the United Kingdom.

Heart transplantation after circulatory death has now become a routine part of the transplant program in many countries, including the United States, Spain, Belgium, the Netherlands, and Austria.

In the United States, 348 DCD heart transplants were performed in 2022, with numbers expected to reach 700 to 800 this year as more centers come online.

It is expected that most countries with heart transplant programs will follow suit and the number of donor hearts will increase by up to 30% worldwide because of DCD.  

Currently, there are about 8,000 heart transplants worldwide each year and with DCD this could rise to about 10,000, potentially an extra 2,000 lives saved each year, experts estimate.  

Two different approaches to DCD heart transplantation have been developed.
 

The direct procurement approach

The Australian group, based at St. Vincent’s Hospital in Sydney, developed a technique referred to as “direct procurement”: after the standoff period and declaration of circulatory death, the chest is opened, and the heart is removed. New technology, the Organ Care System (OCS) heart box (Transmedics), is then used to reperfuse and restart the heart outside the body so its suitability for transplant can be assessed.

The heart is kept perfused and beating in the OCS box while it is being transported to the recipient. This has enabled longer transit times than the traditional way of transporting the nonbeating heart on ice.

Peter MacDonald, MD, PhD, from the St Vincent’s group that developed this approach, said, “Most people thought a heart from a DCD donor would not survive transport – that the injury to the heart from the combination of life support withdrawal, stand-off time, and cold storage would be too much. But we modeled the process in the lab and were able to show that we were able to get the heart beating again after withdrawal of life support.”

Dr. McDonald noted that “the recipient of their first human DCD heart transplant using this machine in 2014 is still alive and well.” The Australian group has now done 85 of these DCD heart transplants, and they have increased the number of heart transplant procedures at St. Vincent’s Hospital by 25%.
 

Normothermic regional perfusion (NRP)  

The U.K. group, based at the Royal Papworth Hospital in Cambridge, England, developed a different approach to DCD: After the standoff period and the declaration of circulatory death, the donor is connected to a heart/lung machine using extracorporeal membrane oxygenation (ECMO) so that the heart is perfused and starts beating again inside the body. This approach is known as normothermic regional perfusion (NRP).

Marius Berman, MD, surgical lead for Transplantation and Mechanical Circulatory Support at Papworth, explained that the NRP approach allows the heart to be perfused and restarted faster than direct procurement, resulting in a shorter ischemic time. The heart can be evaluated thoroughly for suitability for transplantation in situ before committing to transplantation, and because the heart is less damaged, it can be transported on ice without use of the OCS box.

“DCD is more complicated than DBD, because the heart has stopped and has to be restarted. Retrieval teams have to be very experienced,” Dr. Berman noted. “This is more of an issue for the direct procurement approach, where the chest has to be opened and the heart retrieved as fast as possible. It is a rush. The longer time without the heart being perfused correlates to an increased incidence of primary graft dysfunction. With NRP, we can get the heart started again more quickly, which is crucial.”

Stephen Large, MBBS, another cardiothoracic surgeon with the Papworth team, added that they have reduced ischemic time to about 15 minutes. “That’s considerably shorter than reperfusing the heart outside the body,” he said. “This results in a healthier organ for the recipient.” 

The NRP approach is also less expensive than direct procurement as one OCS box costs about $75,000.

He pointed out that the NRP approach can also be used for heart transplants in children and even small babies, while currently the direct procurement technique is not typically suitable for children because the OCS box was not designed for small hearts. 

DCD, using either technique, has increased the heart transplant rate by 40% at Papworth, and is being used at all seven transplant centers in the United Kingdom, “a world first,” noted Dr. Large.

The Papworth team recently published its 5-year experience with 25 NRP transplants and 85 direct procurement transplants. Survival in recipients was no different, although there was some suggestion that the NRP hearts may have been in slightly better condition, possibly being more resistant to immunological rejection.
 

Ethical concerns about NRP

Restarting the circulation during the NRP process has raised ethical concerns.

When the NRP technique was first used in the United States, these ethical questions were raised by several groups, including the American College of Physicians (ACP).

Harry Peled, MD, Providence St. Jude Medical Center, Fullerton, Calif., coauthor of a recent Viewpoint on the issue, is board-certified in both cardiology and critical care, and said he is a supporter of DCD using direct procurement, but he does not believe that NRP is ethical at present. He is not part of the ACP, but said his views align with those of the organization.

There are two ethical problems with NRP, he said. The first is whether by restarting the circulation, the NRP process violates the U.S. definition of death, and retrieval of organs would therefore violate the dead donor rule. 

“American law states that death is the irreversible cessation of brain function or of circulatory function. But with NRP, the circulation is artificially restored, so the cessation of circulatory function is not irreversible,” Dr. Peled pointed out.

“I have no problem with DCD using direct procurement as we are not restarting the circulation. But NRP is restarting the circulation and that is a problem for me,” Dr. Peled said. “I would argue that by performing NRP, we are resuscitating the patient.”

The second ethical problem with NRP is concern about whether, during the process, there would be any circulation to the brain, and if so, would this be enough to restore some brain function? Before NRP is started, the main arch vessel arteries to the head are clamped to prevent flow to the brain, but there are worries that some blood flow may still be possible through small collateral vessels.

“We have established that these patients do not have enough brain function for a meaningful life, which is why a decision has been made to remove life support, but they have not been declared brain dead,” Dr. Peled said.

With direct procurement, the circulation is not restarted so there is no chance that any brain function will be restored, he said. “But with NRP, because the arch vessels have to be clamped to prevent brain circulation, that is admitting there is concern that brain function may be restored if circulation to the brain is reestablished, and brain function is compatible with life. As we do not know whether there is any meaningful circulation to the brain via the small collaterals, there is, in effect, a risk of bringing the patient back to life.”

The other major concern for some is whether even a very small amount of circulation to the brain would be enough to support consciousness, and “we don’t know that for certain,” Dr. Peled said.
 

The argument for NRP

Nader Moazami, MD, professor of cardiovascular surgery, NYU Langone Health, New York, is one of the more vocal proponents of NRP for DCD heart transplantation in the United States, and has coauthored responses to these ethical concerns.

“People are confusing many issues to produce an argument against NRP,” he said.

“Our position is that death has already been declared based on the lack of circulatory function for over 5 minutes and this has been with the full agreement of the family, knowing that the patient has no chance of a meaningful life. No one is thinking of trying to resuscitate the patient. It has already been established that any future efforts to resuscitate are futile. In this case, we are not resuscitating the patient by restarting the circulation. It is just regional perfusion of the organs.”

Dr. Moazami pointed out this concept was accepted for the practice of abdominal DCD when it first started in the United States in the 1990s where cold perfusion was used to preserve the abdominal organs before they were retrieved from the body.

“The new approach of using NRP is similar except that it involves circulating warm blood, which will preserve organs better and result in higher quality organs for the recipient.”

On the issue of concern about possible circulation to the brain, Dr. Moazami said: “The ethical critics of NRP are questioning whether the brain may not be dead. We are arguing that the patient has already been declared dead as they have had a circulatory death. You cannot die twice.”

He maintained that the clamping of the arch vessels to the head will ensure that when the circulation is restarted “the natural process of circulatory death leading to brain death will continue to progress.” 

On the concerns about possible collateral flow to the brain, Dr. Moazami said there is no evidence that this occurs. “Prominent neurologists have said it is impossible for collaterals to provide any meaningful blood flow to the brain in this situation. And even if there is small amount of blood flow to the brain, this would be insufficient to maintain any meaningful brain function.”

But Dr. Peled argues that this has not been proved. “Even though we don’t think there is enough circulation to the brain for any function with NRP, we don’t know that with 100% certainty,” he said. “In my view, if there is a possibility of even the smallest amount of brain flow, we are going against the dead donor rule. We are rewriting the rules of death.”

Dr. Moazami countered: “Nothing in life is 100%, particularly in medicine. With that argument can you also prove with 100% certainty to me that there is absolutely no brain function with regular direct procurement DCD?  We know that brain death has started, but the question is: Has it been completed? We don’t know the answer to this question with 100% certainty, but that is the case for regular direct procurement DCD as well, and that has been accepted by almost everyone.

“The whole issue revolves around when are we comfortable that death has occurred,” he said. “Those against NRP are concerned that organs are being taken before the patient is dead. But the key point is that the patient has already been declared dead.”

Since there is some concern over the ethics of NRP, why not just stick to DCD with direct procurement?

Dr. Moazami argued that NRP results in healthier organs. “NRP allows more successful heart transplants, liver transplants, lung transplants. It preserves all the organs better,” he said. “This will have a big impact on recipients – they would obviously much prefer a healthier organ. In addition, the process is easier and cheaper, so more centers will be able to do it, therefore more transplants will get done and more lives will be saved if NRP is used.”

He added: “I am a physician taking care of sick patients. I believe I have to respect the wishes of the donor and the donor family; make sure I’m not doing any harm to the donor; and ensure the best quality possible of the organ I am retrieving to best serve the recipient. I am happy I am doing this by using NRP for DCD heart transplantation.”

But Dr. Peled argued that while NRP may have some possible advantages over direct procurement, that does not justify allowing a process to go ahead that is unethical.

“The fact that NRP may result in some benefits doesn’t justify violating the dead donor rule or the possibility, however small, of causing pain to the donor. If it’s unethical, it’s unethical. Full stop,” he said.

“I feel that NRP is not respecting the rights of our patients and that the process does not have adequate transparency. We took it to our local ethics committee, and they decided not to approve NRP in our health care system. I agree with this decision,” Dr. Peled said.  

“The trouble is different experts and different countries are not in agreement about this,” he added. “Reasonable, well-informed people are in disagreement. I do not believe we can have a standard of care where there is not consensus.”
 

Cautious nod

In a 2022 consensus statement, the International Society for Heart and Lung Transplantation (ISHLT) gave a cautious nod toward DCD and NRP, dependent on local recommendations.

The ISHLT conclusion reads: “With appropriate consideration of the ethical principles involved in organ donation, DCD can be undertaken in a morally permissible manner. In all cases, the introduction of DCD programs should be in accordance with local legal regulations. Countries lacking a DCD pathway should be encouraged to develop national ethical, professional, and legal frameworks to address both public and professional concerns.”

The author of a recent editorial on the subject, Ulrich P. Jorde, MD, head of the heart transplant program at Montefiore Medical Center, New York, said, “DCD is a great step forward. People regularly die on the heart transplant waiting list. DCD will increase the supply of donor hearts by 20% to 30%.”

However, he noted that while most societies have agreed on a protocol for organ donation based on brain death, the situation is more complicated with circulatory death.

“Different countries have different definitions of circulatory death. How long do we have to wait after the heart has stopped beating before the patient is declared dead? Most countries have agreed on 5 minutes, but other countries have imposed different periods and as such, different definitions of death.

“The ISHLT statement says that restarting the circulation is acceptable if death has been certified according to prevailing law and surgical interventions are undertaken to preclude any restoration of cerebral circulation. But our problem is that different regional societies have different definitions of circulatory, death which makes the situation confusing.”

Dr. Jorde added: “We also have to weigh the wishes of the donor and their family. If family, advocating what are presumed to be the donor’s wishes, have decided that DCD would be acceptable and they understand the concept and wish to donate the organs after circulatory death, this should be strongly considered under the concept of self-determination, a basic human right.”
 

Variations in practice around the world 

This ethical debate has led to large variations in practice around the world, with some countries, such as Spain, allowing both methods of DCD, while Australia allows direct procurement but not NRP, and Germany currently does not allow DCD at all.

In the United States, things are even more complicated, with some states allowing NRP while others don’t. Even within states, some hospitals and transplant organizations allow NRP, and others don’t. 

David A. D’Alessandro, MD, cardiac surgeon at Massachusetts General Hospital, Boston, uses only the direct procurement approach as his region does not allow NRP.

“The direct procurement approach is not controversial and to me that’s a big advantage. I believe we need to agree on the ethics first, and then get into a debate about which technique is better,” he told this news organization.

Dr. D’Alessandro and his group recently published the results of their study, with direct procurement DCD heart transplantation showing similar short-term clinical outcomes to DBD.

“We are only doing direct procurement and we are seeing good results that appear to be comparable to DBD. That is good enough for me,” he said.

Dr. D’Alessandro estimates that in the United States both types of DCD procedures are currently being done about equally.

“Anything we can do to increase the amount of hearts available for transplantation is a big deal,” he said. “At the moment, only the very sickest patients get a heart transplant, and many patients die on the transplant waiting list. Very sadly, many young people die every year from a circulatory death after having life support withdrawn. Before DCD, these beautiful functional organs were not able to be used. Now we have a way of saving lives with these organs.”

Dr. D’Alessandro noted that more and more centers in the United States are starting to perform DCD heart transplants. 

“Not every transplant center may join in as the DCD procedures are very resource-intensive and time-consuming. For low-volume transplant centers, it may not be worth the expense and anguish to do DCD heart transplants. But bigger centers will need to engage in DCD to remain competitive. My guess is that 50%-70% of U.S. transplant centers will do DCD in future.”

He said he thinks it is a “medical shortcoming” that agreement cannot be reached on the ethics of NRP. “In an ideal world everyone would be on the same page. It makes me a bit uncomfortable that some people think it’s okay and some people don’t.”

Adam DeVore, MD, a cardiologist at Duke University Medical Center, Durham, N.C., the first U.S. center to perform an adult DCD heart transplant, reported that his institution uses both methods, with the choice sometimes depending on how far the heart must travel.

“If the recipient is near, NRP may be chosen as the heart is transported on ice, but if it needs to go further away we are more likely to choose direct procurement and use of the OCS box,” he said. 

“I am really proud of what we’ve been able to do, helping to introduce DCD in the U.S.,” Dr. DeVore said. “This is having a massive benefit in increasing the number of hearts for donation with great outcomes.”  

But he acknowledged that the whole concept of DCD is somewhat controversial.  

“The idea of brain death really came about for the purpose of heart donation. The two things are very intricately tied. Trying to do heart donation without brain death having been declared is foreign to people. Also, in DCD there is the issue of [this]: When life support is removed, how long do we wait before death can be declared? That could be in conflict with how long the organ needs to remain viable. We are going through the process now of looking at these questions. There is a lot of variation in the U.S. about the withdrawal of care and the declaration of death, which is not completely standardized.

“But the concept of circulatory death itself is accepted after the withdrawal of life support. I think it’s the rush to take the organs out that makes it more difficult.”

Dr. DeVore said the field is moving forward now. “As the process has become more common, people have become more comfortable, probably because of the big difference it will make to saving lives. But we do need to try and standardize best practices.”

A recent Canadian review of the ethics of DCD concluded that the direct procurement approach would be in alignment with current medical guidelines, but that further work is required to evaluate the consistency of NRP with current Canadian death determination policy and to ensure the absence of brain perfusion during this process.

In the United Kingdom, the definition of death is brain-based, and brain death is defined on a neurological basis.

Dr. Stephen Large from Papworth explained that this recognizes the presence of brain-stem death through brain stem reflex testing after the withdrawal of life support, cardiorespiratory arrest and 5 further minutes of ischemia. As long as NRP does not restore intracranial (brainstem) perfusion after death has been confirmed, then it is consistent with laws for death determination and therefore both direct procurement and NRP are permissible.

However, the question over possible collateral flow to the brain has led the United Kingdom to pause the NRP technique as routine practice while this is investigated further. So, at the present time, the vast majority of DCD heart transplants are being conducted using the direct procurement approach.

But the United Kingdom is facing the bigger challenge: national funding that will soon end. “The DCD program in the U.K. has been extremely successful, increasing heart transplant rates by up to 28%,” Dr. Berman said. “Everybody wants it to continue. But at present the DCD program only has national funding in the U.K. until March 2023. We don’t know what will happen after that.”

The current model in the United Kingdom consists of three specialized DCD heart retrieval teams, a national protocol of direct organ procurement and delivery of DCD hearts to all seven transplant programs, both adult and pediatric.

If the national funding is not extended, “we will go back to individual hospitals trying to fund their own programs. That will be a serious threat to the program and could result in a large reduction in heart transplants,” said Dr. Berman.
 

Definition of death  

The crux of the issue with regard to NRP seems to be variations in how death is defined and the interpretation of those definitions.  

DCD donors will have had many tests indicating severe brain damage, a neurologist will have declared the prognosis is futile, and relatives will have agreed to withdraw life support, Dr. Jorde said. “The heart stops beating, and the stand-off time means that blood flow to the brain ceases completely for at least 5 minutes before circulatory death is declared. This is enough on its own to stop brain function.”

Dr. Large made the point that by the time the circulation is reestablished with NRP, more time has elapsed, and the brain will have been without perfusion for much longer than 5 minutes, so it would be “physiologically almost impossible” for there to be any blood flow to the brain.

“Because these brains are already very damaged before life support was removed, the intracranial pressure is high, which will further discourage blood flow to the brain,” he said. Then the donor goes through a period of anoxic heart arrest, up to 16 minutes at a minimum of no blood supply, enough on its own to stop meaningful brain function. 

“It’s asking an awful lot to believe that there might be any brain function left,” he said. “And if, on reestablishing the circulation with NRP, there is any blood in the collaterals, the pressure of such flow is so low it won’t enter the brain.”

Dr. Large also pointed out that the fact that the United Kingdom requires a neurologic definition for brain-stem death makes the process easier. 

In Australia, St. Vincent’s cardiologist Dr. MacDonald noted that death is defined as the irreversible cessation of circulation, so the NRP procedure is not allowed.

“With NRP, there is an ethical dilemma over whether the patient has legally died or not. Different countries have different ways of defining death. Perhaps society will have to review of the definition of death,” he suggested. Death is a process, “but for organ donation, we have to choose a moment in time of that process that satisfies everyone – when there is no prospect of recovery of the donor but the organs can still be utilized without harming the donor.” 

Dr. MacDonald said the field is in transition. “I don’t want to argue that one technique is better than the other; I think it’s good to have access to both techniques. Anything that will increase the number of transplants we can do is a good thing.”
 

Collaborative decision

Everyone seems to agree that there should be an effort to try to define death in a uniform way worldwide, and that international, national and local regulations are aligned with each other.

Dr. Jorde said: “It is of critical importance that local guidelines are streamlined, firstly in any one given country and then globally, and these things must be discussed transparently within society with all stakeholders – doctors, patients, citizens.”

Dr. Peled, from Providence St. Jude in California, concurred: “There is the possibility that we could change the definition of death, but that cannot be a decision based solely on transplant organizations. It has to be a collaborative decision with a large input from groups who do not have an interest in the procurement of organs.”

He added: “The dialogue so far has been civil, and everybody is trying to do the right thing. My hope is that as a civilized society we will figure out a way forward. At present, there is significant controversy about NRP, and families need to know that. My main concern is that if there is any lack of transparency in getting informed consent, then this risks people losing trust in the donation system.” 

Dr. Moazami, from NYU Langone, said the controversy has cast a cloud over the practice of NRP throughout the world. “We need to get it sorted out.”

He said he believes the way forward is to settle the question of whether there is any meaningful blood flow to the brain with the NRP technique.

“This is where the research has to focus. I believe this concern is hypothetical, but I am happy to do the studies to confirm that. Then, the issue should come to a rest. I think that is the right way forward – to do the studies rather than enforcing a moratorium on the practice because of a hypothetical concern.”

These studies on blood flow to the brain are now getting started in both the United Kingdom and the United States.

The U.K. study is being run by Antonio Rubino, MD, consultant in cardiothoracic anesthesia and intensive care at Papworth Hospital NHS Foundation and clinical lead, organ donation. Dr. Rubino explained that the study will assess cerebral blood flow using CT angiography of the brain. “We hypothesize that this will provide evidence to indicate that brain blood flow is not present during NRP and promote trust in the use of NRP in routine practice,” he said.

Dr. Large said: “Rather than having these tortured arguments, we will do the measurements. For the sake of society in this situation, I think it’s good to stop and take a breath. We must measure this, and we are doing just that.”

If there is any blood flow at all, Dr. Large said they will then have to seek expert guidance. “Say we find there is 50 mL of blood flow and normal blood flow is 1,500 mL/min. We will need expert guidance on whether it is remotely possible to be sentient on that. I would say it would be extraordinarily unlikely.”  

Dr. Berman summarized the situation: “DCD is increasing the availability of hearts for transplant. This is saving lives, reducing the number of patients on the waiting list, and reducing hospital stays for patients unable to leave the hospital without a transplant. It is definitely here to stay. It is crucial that it gets funded properly, and it is also crucial that we resolve the NRP ethical issues as soon as possible.”

He is hopeful that some of these issues will be resolved this year.

Dr. MacDonald reported he has received “in-kind” support from Transmedics through provision of research modules for preclinical research studies. Dr. D’Alessandro reported he is on the speakers bureau for Abiomed, not relevant to this article. No other relevant disclosures were reported.
 

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

The relatively recent innovation of heart transplantation after circulatory death of the donor is increasing the number of donor hearts available and leading to many more lives on the heart transplant waiting list being saved. Experts agree it’s a major and very welcome advance in medicine.

However, some of the processes involved in one approach to donation after circulatory death has raised ethical concerns and questions about whether they violate the “dead donor rule” – a principle that requires patients be declared dead before removal of life-sustaining organs for transplant.  

Rasi Bhadramani/iStock/Getty Images

Experts in the fields of transplantation and medical ethics have yet to reach consensus, causing problems for the transplant community, who worry that this could cause a loss of confidence in the entire transplant process.
 

A new pathway for heart transplantation

The traditional approach to transplantation is to retrieve organs from a donor who has been declared brain dead, known as “donation after brain death (DBD).” These patients have usually suffered a catastrophic brain injury but survived to get to intensive care.

As the brain swells because of injury, it becomes evident that all brain function is lost, and the patient is declared brain dead. However, breathing is maintained by the ventilator and the heart is still beating. Because the organs are being oxygenated, there is no immediate rush to retrieve the organs and the heart can be evaluated for its suitability for transplant in a calm and methodical way before it is removed.  

However, there is a massive shortage of organs, especially hearts, partially because of the limited number of donors who are declared brain dead in that setting.

In recent years, another pathway for organ transplantation has become available: “donation after circulatory death (DCD).” These patients also have suffered a catastrophic brain injury considered to be nonsurvivable, but unlike the DBD situation, the brain still has some function, so the patient does not meet the criteria for brain death. 

Still, because the patient is considered to have no chance of a meaningful recovery, the family often recognizes the futility of treatment and agrees to the withdrawal of life support. When this happens, the heart normally stops beating after a period of time. There is then a “stand-off time” – normally 5 minutes – after which death is declared and the organs can be removed. 

The difficulty with this approach, however, is that because the heart has been stopped, it has been deprived of oxygen, potentially causing injury. While DCD has been practiced for several years to retrieve organs such as the kidney, liver, lungs, and pancreas, the heart is more difficult as it is more susceptible to oxygen deprivation. And for the heart to be assessed for transplant suitability, it should ideally be beating, so it has to be reperfused and restarted quickly after death has been declared.

For many years it was thought the oxygen deprivation that occurs after circulatory death would be too much to provide a functional organ. But researchers in the United Kingdom and Australia developed techniques to overcome this problem, and early DCD heart transplants took place in 2014 in Australia, and in 2015 in the United Kingdom.

Heart transplantation after circulatory death has now become a routine part of the transplant program in many countries, including the United States, Spain, Belgium, the Netherlands, and Austria.

In the United States, 348 DCD heart transplants were performed in 2022, with numbers expected to reach 700 to 800 this year as more centers come online.

It is expected that most countries with heart transplant programs will follow suit and the number of donor hearts will increase by up to 30% worldwide because of DCD.  

Currently, there are about 8,000 heart transplants worldwide each year and with DCD this could rise to about 10,000, potentially an extra 2,000 lives saved each year, experts estimate.  

Two different approaches to DCD heart transplantation have been developed.
 

The direct procurement approach

The Australian group, based at St. Vincent’s Hospital in Sydney, developed a technique referred to as “direct procurement”: after the standoff period and declaration of circulatory death, the chest is opened, and the heart is removed. New technology, the Organ Care System (OCS) heart box (Transmedics), is then used to reperfuse and restart the heart outside the body so its suitability for transplant can be assessed.

The heart is kept perfused and beating in the OCS box while it is being transported to the recipient. This has enabled longer transit times than the traditional way of transporting the nonbeating heart on ice.

Peter MacDonald, MD, PhD, from the St Vincent’s group that developed this approach, said, “Most people thought a heart from a DCD donor would not survive transport – that the injury to the heart from the combination of life support withdrawal, stand-off time, and cold storage would be too much. But we modeled the process in the lab and were able to show that we were able to get the heart beating again after withdrawal of life support.”

Dr. McDonald noted that “the recipient of their first human DCD heart transplant using this machine in 2014 is still alive and well.” The Australian group has now done 85 of these DCD heart transplants, and they have increased the number of heart transplant procedures at St. Vincent’s Hospital by 25%.
 

Normothermic regional perfusion (NRP)  

The U.K. group, based at the Royal Papworth Hospital in Cambridge, England, developed a different approach to DCD: After the standoff period and the declaration of circulatory death, the donor is connected to a heart/lung machine using extracorporeal membrane oxygenation (ECMO) so that the heart is perfused and starts beating again inside the body. This approach is known as normothermic regional perfusion (NRP).

Marius Berman, MD, surgical lead for Transplantation and Mechanical Circulatory Support at Papworth, explained that the NRP approach allows the heart to be perfused and restarted faster than direct procurement, resulting in a shorter ischemic time. The heart can be evaluated thoroughly for suitability for transplantation in situ before committing to transplantation, and because the heart is less damaged, it can be transported on ice without use of the OCS box.

“DCD is more complicated than DBD, because the heart has stopped and has to be restarted. Retrieval teams have to be very experienced,” Dr. Berman noted. “This is more of an issue for the direct procurement approach, where the chest has to be opened and the heart retrieved as fast as possible. It is a rush. The longer time without the heart being perfused correlates to an increased incidence of primary graft dysfunction. With NRP, we can get the heart started again more quickly, which is crucial.”

Stephen Large, MBBS, another cardiothoracic surgeon with the Papworth team, added that they have reduced ischemic time to about 15 minutes. “That’s considerably shorter than reperfusing the heart outside the body,” he said. “This results in a healthier organ for the recipient.” 

The NRP approach is also less expensive than direct procurement as one OCS box costs about $75,000.

He pointed out that the NRP approach can also be used for heart transplants in children and even small babies, while currently the direct procurement technique is not typically suitable for children because the OCS box was not designed for small hearts. 

DCD, using either technique, has increased the heart transplant rate by 40% at Papworth, and is being used at all seven transplant centers in the United Kingdom, “a world first,” noted Dr. Large.

The Papworth team recently published its 5-year experience with 25 NRP transplants and 85 direct procurement transplants. Survival in recipients was no different, although there was some suggestion that the NRP hearts may have been in slightly better condition, possibly being more resistant to immunological rejection.
 

Ethical concerns about NRP

Restarting the circulation during the NRP process has raised ethical concerns.

When the NRP technique was first used in the United States, these ethical questions were raised by several groups, including the American College of Physicians (ACP).

Harry Peled, MD, Providence St. Jude Medical Center, Fullerton, Calif., coauthor of a recent Viewpoint on the issue, is board-certified in both cardiology and critical care, and said he is a supporter of DCD using direct procurement, but he does not believe that NRP is ethical at present. He is not part of the ACP, but said his views align with those of the organization.

There are two ethical problems with NRP, he said. The first is whether by restarting the circulation, the NRP process violates the U.S. definition of death, and retrieval of organs would therefore violate the dead donor rule. 

“American law states that death is the irreversible cessation of brain function or of circulatory function. But with NRP, the circulation is artificially restored, so the cessation of circulatory function is not irreversible,” Dr. Peled pointed out.

“I have no problem with DCD using direct procurement as we are not restarting the circulation. But NRP is restarting the circulation and that is a problem for me,” Dr. Peled said. “I would argue that by performing NRP, we are resuscitating the patient.”

The second ethical problem with NRP is concern about whether, during the process, there would be any circulation to the brain, and if so, would this be enough to restore some brain function? Before NRP is started, the main arch vessel arteries to the head are clamped to prevent flow to the brain, but there are worries that some blood flow may still be possible through small collateral vessels.

“We have established that these patients do not have enough brain function for a meaningful life, which is why a decision has been made to remove life support, but they have not been declared brain dead,” Dr. Peled said.

With direct procurement, the circulation is not restarted so there is no chance that any brain function will be restored, he said. “But with NRP, because the arch vessels have to be clamped to prevent brain circulation, that is admitting there is concern that brain function may be restored if circulation to the brain is reestablished, and brain function is compatible with life. As we do not know whether there is any meaningful circulation to the brain via the small collaterals, there is, in effect, a risk of bringing the patient back to life.”

The other major concern for some is whether even a very small amount of circulation to the brain would be enough to support consciousness, and “we don’t know that for certain,” Dr. Peled said.
 

The argument for NRP

Nader Moazami, MD, professor of cardiovascular surgery, NYU Langone Health, New York, is one of the more vocal proponents of NRP for DCD heart transplantation in the United States, and has coauthored responses to these ethical concerns.

“People are confusing many issues to produce an argument against NRP,” he said.

“Our position is that death has already been declared based on the lack of circulatory function for over 5 minutes and this has been with the full agreement of the family, knowing that the patient has no chance of a meaningful life. No one is thinking of trying to resuscitate the patient. It has already been established that any future efforts to resuscitate are futile. In this case, we are not resuscitating the patient by restarting the circulation. It is just regional perfusion of the organs.”

Dr. Moazami pointed out this concept was accepted for the practice of abdominal DCD when it first started in the United States in the 1990s where cold perfusion was used to preserve the abdominal organs before they were retrieved from the body.

“The new approach of using NRP is similar except that it involves circulating warm blood, which will preserve organs better and result in higher quality organs for the recipient.”

On the issue of concern about possible circulation to the brain, Dr. Moazami said: “The ethical critics of NRP are questioning whether the brain may not be dead. We are arguing that the patient has already been declared dead as they have had a circulatory death. You cannot die twice.”

He maintained that the clamping of the arch vessels to the head will ensure that when the circulation is restarted “the natural process of circulatory death leading to brain death will continue to progress.” 

On the concerns about possible collateral flow to the brain, Dr. Moazami said there is no evidence that this occurs. “Prominent neurologists have said it is impossible for collaterals to provide any meaningful blood flow to the brain in this situation. And even if there is small amount of blood flow to the brain, this would be insufficient to maintain any meaningful brain function.”

But Dr. Peled argues that this has not been proved. “Even though we don’t think there is enough circulation to the brain for any function with NRP, we don’t know that with 100% certainty,” he said. “In my view, if there is a possibility of even the smallest amount of brain flow, we are going against the dead donor rule. We are rewriting the rules of death.”

Dr. Moazami countered: “Nothing in life is 100%, particularly in medicine. With that argument can you also prove with 100% certainty to me that there is absolutely no brain function with regular direct procurement DCD?  We know that brain death has started, but the question is: Has it been completed? We don’t know the answer to this question with 100% certainty, but that is the case for regular direct procurement DCD as well, and that has been accepted by almost everyone.

“The whole issue revolves around when are we comfortable that death has occurred,” he said. “Those against NRP are concerned that organs are being taken before the patient is dead. But the key point is that the patient has already been declared dead.”

Since there is some concern over the ethics of NRP, why not just stick to DCD with direct procurement?

Dr. Moazami argued that NRP results in healthier organs. “NRP allows more successful heart transplants, liver transplants, lung transplants. It preserves all the organs better,” he said. “This will have a big impact on recipients – they would obviously much prefer a healthier organ. In addition, the process is easier and cheaper, so more centers will be able to do it, therefore more transplants will get done and more lives will be saved if NRP is used.”

He added: “I am a physician taking care of sick patients. I believe I have to respect the wishes of the donor and the donor family; make sure I’m not doing any harm to the donor; and ensure the best quality possible of the organ I am retrieving to best serve the recipient. I am happy I am doing this by using NRP for DCD heart transplantation.”

But Dr. Peled argued that while NRP may have some possible advantages over direct procurement, that does not justify allowing a process to go ahead that is unethical.

“The fact that NRP may result in some benefits doesn’t justify violating the dead donor rule or the possibility, however small, of causing pain to the donor. If it’s unethical, it’s unethical. Full stop,” he said.

“I feel that NRP is not respecting the rights of our patients and that the process does not have adequate transparency. We took it to our local ethics committee, and they decided not to approve NRP in our health care system. I agree with this decision,” Dr. Peled said.  

“The trouble is different experts and different countries are not in agreement about this,” he added. “Reasonable, well-informed people are in disagreement. I do not believe we can have a standard of care where there is not consensus.”
 

Cautious nod

In a 2022 consensus statement, the International Society for Heart and Lung Transplantation (ISHLT) gave a cautious nod toward DCD and NRP, dependent on local recommendations.

The ISHLT conclusion reads: “With appropriate consideration of the ethical principles involved in organ donation, DCD can be undertaken in a morally permissible manner. In all cases, the introduction of DCD programs should be in accordance with local legal regulations. Countries lacking a DCD pathway should be encouraged to develop national ethical, professional, and legal frameworks to address both public and professional concerns.”

The author of a recent editorial on the subject, Ulrich P. Jorde, MD, head of the heart transplant program at Montefiore Medical Center, New York, said, “DCD is a great step forward. People regularly die on the heart transplant waiting list. DCD will increase the supply of donor hearts by 20% to 30%.”

However, he noted that while most societies have agreed on a protocol for organ donation based on brain death, the situation is more complicated with circulatory death.

“Different countries have different definitions of circulatory death. How long do we have to wait after the heart has stopped beating before the patient is declared dead? Most countries have agreed on 5 minutes, but other countries have imposed different periods and as such, different definitions of death.

“The ISHLT statement says that restarting the circulation is acceptable if death has been certified according to prevailing law and surgical interventions are undertaken to preclude any restoration of cerebral circulation. But our problem is that different regional societies have different definitions of circulatory, death which makes the situation confusing.”

Dr. Jorde added: “We also have to weigh the wishes of the donor and their family. If family, advocating what are presumed to be the donor’s wishes, have decided that DCD would be acceptable and they understand the concept and wish to donate the organs after circulatory death, this should be strongly considered under the concept of self-determination, a basic human right.”
 

Variations in practice around the world 

This ethical debate has led to large variations in practice around the world, with some countries, such as Spain, allowing both methods of DCD, while Australia allows direct procurement but not NRP, and Germany currently does not allow DCD at all.

In the United States, things are even more complicated, with some states allowing NRP while others don’t. Even within states, some hospitals and transplant organizations allow NRP, and others don’t. 

David A. D’Alessandro, MD, cardiac surgeon at Massachusetts General Hospital, Boston, uses only the direct procurement approach as his region does not allow NRP.

“The direct procurement approach is not controversial and to me that’s a big advantage. I believe we need to agree on the ethics first, and then get into a debate about which technique is better,” he told this news organization.

Dr. D’Alessandro and his group recently published the results of their study, with direct procurement DCD heart transplantation showing similar short-term clinical outcomes to DBD.

“We are only doing direct procurement and we are seeing good results that appear to be comparable to DBD. That is good enough for me,” he said.

Dr. D’Alessandro estimates that in the United States both types of DCD procedures are currently being done about equally.

“Anything we can do to increase the amount of hearts available for transplantation is a big deal,” he said. “At the moment, only the very sickest patients get a heart transplant, and many patients die on the transplant waiting list. Very sadly, many young people die every year from a circulatory death after having life support withdrawn. Before DCD, these beautiful functional organs were not able to be used. Now we have a way of saving lives with these organs.”

Dr. D’Alessandro noted that more and more centers in the United States are starting to perform DCD heart transplants. 

“Not every transplant center may join in as the DCD procedures are very resource-intensive and time-consuming. For low-volume transplant centers, it may not be worth the expense and anguish to do DCD heart transplants. But bigger centers will need to engage in DCD to remain competitive. My guess is that 50%-70% of U.S. transplant centers will do DCD in future.”

He said he thinks it is a “medical shortcoming” that agreement cannot be reached on the ethics of NRP. “In an ideal world everyone would be on the same page. It makes me a bit uncomfortable that some people think it’s okay and some people don’t.”

Adam DeVore, MD, a cardiologist at Duke University Medical Center, Durham, N.C., the first U.S. center to perform an adult DCD heart transplant, reported that his institution uses both methods, with the choice sometimes depending on how far the heart must travel.

“If the recipient is near, NRP may be chosen as the heart is transported on ice, but if it needs to go further away we are more likely to choose direct procurement and use of the OCS box,” he said. 

“I am really proud of what we’ve been able to do, helping to introduce DCD in the U.S.,” Dr. DeVore said. “This is having a massive benefit in increasing the number of hearts for donation with great outcomes.”  

But he acknowledged that the whole concept of DCD is somewhat controversial.  

“The idea of brain death really came about for the purpose of heart donation. The two things are very intricately tied. Trying to do heart donation without brain death having been declared is foreign to people. Also, in DCD there is the issue of [this]: When life support is removed, how long do we wait before death can be declared? That could be in conflict with how long the organ needs to remain viable. We are going through the process now of looking at these questions. There is a lot of variation in the U.S. about the withdrawal of care and the declaration of death, which is not completely standardized.

“But the concept of circulatory death itself is accepted after the withdrawal of life support. I think it’s the rush to take the organs out that makes it more difficult.”

Dr. DeVore said the field is moving forward now. “As the process has become more common, people have become more comfortable, probably because of the big difference it will make to saving lives. But we do need to try and standardize best practices.”

A recent Canadian review of the ethics of DCD concluded that the direct procurement approach would be in alignment with current medical guidelines, but that further work is required to evaluate the consistency of NRP with current Canadian death determination policy and to ensure the absence of brain perfusion during this process.

In the United Kingdom, the definition of death is brain-based, and brain death is defined on a neurological basis.

Dr. Stephen Large from Papworth explained that this recognizes the presence of brain-stem death through brain stem reflex testing after the withdrawal of life support, cardiorespiratory arrest and 5 further minutes of ischemia. As long as NRP does not restore intracranial (brainstem) perfusion after death has been confirmed, then it is consistent with laws for death determination and therefore both direct procurement and NRP are permissible.

However, the question over possible collateral flow to the brain has led the United Kingdom to pause the NRP technique as routine practice while this is investigated further. So, at the present time, the vast majority of DCD heart transplants are being conducted using the direct procurement approach.

But the United Kingdom is facing the bigger challenge: national funding that will soon end. “The DCD program in the U.K. has been extremely successful, increasing heart transplant rates by up to 28%,” Dr. Berman said. “Everybody wants it to continue. But at present the DCD program only has national funding in the U.K. until March 2023. We don’t know what will happen after that.”

The current model in the United Kingdom consists of three specialized DCD heart retrieval teams, a national protocol of direct organ procurement and delivery of DCD hearts to all seven transplant programs, both adult and pediatric.

If the national funding is not extended, “we will go back to individual hospitals trying to fund their own programs. That will be a serious threat to the program and could result in a large reduction in heart transplants,” said Dr. Berman.
 

Definition of death  

The crux of the issue with regard to NRP seems to be variations in how death is defined and the interpretation of those definitions.  

DCD donors will have had many tests indicating severe brain damage, a neurologist will have declared the prognosis is futile, and relatives will have agreed to withdraw life support, Dr. Jorde said. “The heart stops beating, and the stand-off time means that blood flow to the brain ceases completely for at least 5 minutes before circulatory death is declared. This is enough on its own to stop brain function.”

Dr. Large made the point that by the time the circulation is reestablished with NRP, more time has elapsed, and the brain will have been without perfusion for much longer than 5 minutes, so it would be “physiologically almost impossible” for there to be any blood flow to the brain.

“Because these brains are already very damaged before life support was removed, the intracranial pressure is high, which will further discourage blood flow to the brain,” he said. Then the donor goes through a period of anoxic heart arrest, up to 16 minutes at a minimum of no blood supply, enough on its own to stop meaningful brain function. 

“It’s asking an awful lot to believe that there might be any brain function left,” he said. “And if, on reestablishing the circulation with NRP, there is any blood in the collaterals, the pressure of such flow is so low it won’t enter the brain.”

Dr. Large also pointed out that the fact that the United Kingdom requires a neurologic definition for brain-stem death makes the process easier. 

In Australia, St. Vincent’s cardiologist Dr. MacDonald noted that death is defined as the irreversible cessation of circulation, so the NRP procedure is not allowed.

“With NRP, there is an ethical dilemma over whether the patient has legally died or not. Different countries have different ways of defining death. Perhaps society will have to review of the definition of death,” he suggested. Death is a process, “but for organ donation, we have to choose a moment in time of that process that satisfies everyone – when there is no prospect of recovery of the donor but the organs can still be utilized without harming the donor.” 

Dr. MacDonald said the field is in transition. “I don’t want to argue that one technique is better than the other; I think it’s good to have access to both techniques. Anything that will increase the number of transplants we can do is a good thing.”
 

Collaborative decision

Everyone seems to agree that there should be an effort to try to define death in a uniform way worldwide, and that international, national and local regulations are aligned with each other.

Dr. Jorde said: “It is of critical importance that local guidelines are streamlined, firstly in any one given country and then globally, and these things must be discussed transparently within society with all stakeholders – doctors, patients, citizens.”

Dr. Peled, from Providence St. Jude in California, concurred: “There is the possibility that we could change the definition of death, but that cannot be a decision based solely on transplant organizations. It has to be a collaborative decision with a large input from groups who do not have an interest in the procurement of organs.”

He added: “The dialogue so far has been civil, and everybody is trying to do the right thing. My hope is that as a civilized society we will figure out a way forward. At present, there is significant controversy about NRP, and families need to know that. My main concern is that if there is any lack of transparency in getting informed consent, then this risks people losing trust in the donation system.” 

Dr. Moazami, from NYU Langone, said the controversy has cast a cloud over the practice of NRP throughout the world. “We need to get it sorted out.”

He said he believes the way forward is to settle the question of whether there is any meaningful blood flow to the brain with the NRP technique.

“This is where the research has to focus. I believe this concern is hypothetical, but I am happy to do the studies to confirm that. Then, the issue should come to a rest. I think that is the right way forward – to do the studies rather than enforcing a moratorium on the practice because of a hypothetical concern.”

These studies on blood flow to the brain are now getting started in both the United Kingdom and the United States.

The U.K. study is being run by Antonio Rubino, MD, consultant in cardiothoracic anesthesia and intensive care at Papworth Hospital NHS Foundation and clinical lead, organ donation. Dr. Rubino explained that the study will assess cerebral blood flow using CT angiography of the brain. “We hypothesize that this will provide evidence to indicate that brain blood flow is not present during NRP and promote trust in the use of NRP in routine practice,” he said.

Dr. Large said: “Rather than having these tortured arguments, we will do the measurements. For the sake of society in this situation, I think it’s good to stop and take a breath. We must measure this, and we are doing just that.”

If there is any blood flow at all, Dr. Large said they will then have to seek expert guidance. “Say we find there is 50 mL of blood flow and normal blood flow is 1,500 mL/min. We will need expert guidance on whether it is remotely possible to be sentient on that. I would say it would be extraordinarily unlikely.”  

Dr. Berman summarized the situation: “DCD is increasing the availability of hearts for transplant. This is saving lives, reducing the number of patients on the waiting list, and reducing hospital stays for patients unable to leave the hospital without a transplant. It is definitely here to stay. It is crucial that it gets funded properly, and it is also crucial that we resolve the NRP ethical issues as soon as possible.”

He is hopeful that some of these issues will be resolved this year.

Dr. MacDonald reported he has received “in-kind” support from Transmedics through provision of research modules for preclinical research studies. Dr. D’Alessandro reported he is on the speakers bureau for Abiomed, not relevant to this article. No other relevant disclosures were reported.
 

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

The relatively recent innovation of heart transplantation after circulatory death of the donor is increasing the number of donor hearts available and leading to many more lives on the heart transplant waiting list being saved. Experts agree it’s a major and very welcome advance in medicine.

However, some of the processes involved in one approach to donation after circulatory death has raised ethical concerns and questions about whether they violate the “dead donor rule” – a principle that requires patients be declared dead before removal of life-sustaining organs for transplant.  

Rasi Bhadramani/iStock/Getty Images

Experts in the fields of transplantation and medical ethics have yet to reach consensus, causing problems for the transplant community, who worry that this could cause a loss of confidence in the entire transplant process.
 

A new pathway for heart transplantation

The traditional approach to transplantation is to retrieve organs from a donor who has been declared brain dead, known as “donation after brain death (DBD).” These patients have usually suffered a catastrophic brain injury but survived to get to intensive care.

As the brain swells because of injury, it becomes evident that all brain function is lost, and the patient is declared brain dead. However, breathing is maintained by the ventilator and the heart is still beating. Because the organs are being oxygenated, there is no immediate rush to retrieve the organs and the heart can be evaluated for its suitability for transplant in a calm and methodical way before it is removed.  

However, there is a massive shortage of organs, especially hearts, partially because of the limited number of donors who are declared brain dead in that setting.

In recent years, another pathway for organ transplantation has become available: “donation after circulatory death (DCD).” These patients also have suffered a catastrophic brain injury considered to be nonsurvivable, but unlike the DBD situation, the brain still has some function, so the patient does not meet the criteria for brain death. 

Still, because the patient is considered to have no chance of a meaningful recovery, the family often recognizes the futility of treatment and agrees to the withdrawal of life support. When this happens, the heart normally stops beating after a period of time. There is then a “stand-off time” – normally 5 minutes – after which death is declared and the organs can be removed. 

The difficulty with this approach, however, is that because the heart has been stopped, it has been deprived of oxygen, potentially causing injury. While DCD has been practiced for several years to retrieve organs such as the kidney, liver, lungs, and pancreas, the heart is more difficult as it is more susceptible to oxygen deprivation. And for the heart to be assessed for transplant suitability, it should ideally be beating, so it has to be reperfused and restarted quickly after death has been declared.

For many years it was thought the oxygen deprivation that occurs after circulatory death would be too much to provide a functional organ. But researchers in the United Kingdom and Australia developed techniques to overcome this problem, and early DCD heart transplants took place in 2014 in Australia, and in 2015 in the United Kingdom.

Heart transplantation after circulatory death has now become a routine part of the transplant program in many countries, including the United States, Spain, Belgium, the Netherlands, and Austria.

In the United States, 348 DCD heart transplants were performed in 2022, with numbers expected to reach 700 to 800 this year as more centers come online.

It is expected that most countries with heart transplant programs will follow suit and the number of donor hearts will increase by up to 30% worldwide because of DCD.  

Currently, there are about 8,000 heart transplants worldwide each year and with DCD this could rise to about 10,000, potentially an extra 2,000 lives saved each year, experts estimate.  

Two different approaches to DCD heart transplantation have been developed.
 

The direct procurement approach

The Australian group, based at St. Vincent’s Hospital in Sydney, developed a technique referred to as “direct procurement”: after the standoff period and declaration of circulatory death, the chest is opened, and the heart is removed. New technology, the Organ Care System (OCS) heart box (Transmedics), is then used to reperfuse and restart the heart outside the body so its suitability for transplant can be assessed.

The heart is kept perfused and beating in the OCS box while it is being transported to the recipient. This has enabled longer transit times than the traditional way of transporting the nonbeating heart on ice.

Peter MacDonald, MD, PhD, from the St Vincent’s group that developed this approach, said, “Most people thought a heart from a DCD donor would not survive transport – that the injury to the heart from the combination of life support withdrawal, stand-off time, and cold storage would be too much. But we modeled the process in the lab and were able to show that we were able to get the heart beating again after withdrawal of life support.”

Dr. McDonald noted that “the recipient of their first human DCD heart transplant using this machine in 2014 is still alive and well.” The Australian group has now done 85 of these DCD heart transplants, and they have increased the number of heart transplant procedures at St. Vincent’s Hospital by 25%.
 

Normothermic regional perfusion (NRP)  

The U.K. group, based at the Royal Papworth Hospital in Cambridge, England, developed a different approach to DCD: After the standoff period and the declaration of circulatory death, the donor is connected to a heart/lung machine using extracorporeal membrane oxygenation (ECMO) so that the heart is perfused and starts beating again inside the body. This approach is known as normothermic regional perfusion (NRP).

Marius Berman, MD, surgical lead for Transplantation and Mechanical Circulatory Support at Papworth, explained that the NRP approach allows the heart to be perfused and restarted faster than direct procurement, resulting in a shorter ischemic time. The heart can be evaluated thoroughly for suitability for transplantation in situ before committing to transplantation, and because the heart is less damaged, it can be transported on ice without use of the OCS box.

“DCD is more complicated than DBD, because the heart has stopped and has to be restarted. Retrieval teams have to be very experienced,” Dr. Berman noted. “This is more of an issue for the direct procurement approach, where the chest has to be opened and the heart retrieved as fast as possible. It is a rush. The longer time without the heart being perfused correlates to an increased incidence of primary graft dysfunction. With NRP, we can get the heart started again more quickly, which is crucial.”

Stephen Large, MBBS, another cardiothoracic surgeon with the Papworth team, added that they have reduced ischemic time to about 15 minutes. “That’s considerably shorter than reperfusing the heart outside the body,” he said. “This results in a healthier organ for the recipient.” 

The NRP approach is also less expensive than direct procurement as one OCS box costs about $75,000.

He pointed out that the NRP approach can also be used for heart transplants in children and even small babies, while currently the direct procurement technique is not typically suitable for children because the OCS box was not designed for small hearts. 

DCD, using either technique, has increased the heart transplant rate by 40% at Papworth, and is being used at all seven transplant centers in the United Kingdom, “a world first,” noted Dr. Large.

The Papworth team recently published its 5-year experience with 25 NRP transplants and 85 direct procurement transplants. Survival in recipients was no different, although there was some suggestion that the NRP hearts may have been in slightly better condition, possibly being more resistant to immunological rejection.
 

Ethical concerns about NRP

Restarting the circulation during the NRP process has raised ethical concerns.

When the NRP technique was first used in the United States, these ethical questions were raised by several groups, including the American College of Physicians (ACP).

Harry Peled, MD, Providence St. Jude Medical Center, Fullerton, Calif., coauthor of a recent Viewpoint on the issue, is board-certified in both cardiology and critical care, and said he is a supporter of DCD using direct procurement, but he does not believe that NRP is ethical at present. He is not part of the ACP, but said his views align with those of the organization.

There are two ethical problems with NRP, he said. The first is whether by restarting the circulation, the NRP process violates the U.S. definition of death, and retrieval of organs would therefore violate the dead donor rule. 

“American law states that death is the irreversible cessation of brain function or of circulatory function. But with NRP, the circulation is artificially restored, so the cessation of circulatory function is not irreversible,” Dr. Peled pointed out.

“I have no problem with DCD using direct procurement as we are not restarting the circulation. But NRP is restarting the circulation and that is a problem for me,” Dr. Peled said. “I would argue that by performing NRP, we are resuscitating the patient.”

The second ethical problem with NRP is concern about whether, during the process, there would be any circulation to the brain, and if so, would this be enough to restore some brain function? Before NRP is started, the main arch vessel arteries to the head are clamped to prevent flow to the brain, but there are worries that some blood flow may still be possible through small collateral vessels.

“We have established that these patients do not have enough brain function for a meaningful life, which is why a decision has been made to remove life support, but they have not been declared brain dead,” Dr. Peled said.

With direct procurement, the circulation is not restarted so there is no chance that any brain function will be restored, he said. “But with NRP, because the arch vessels have to be clamped to prevent brain circulation, that is admitting there is concern that brain function may be restored if circulation to the brain is reestablished, and brain function is compatible with life. As we do not know whether there is any meaningful circulation to the brain via the small collaterals, there is, in effect, a risk of bringing the patient back to life.”

The other major concern for some is whether even a very small amount of circulation to the brain would be enough to support consciousness, and “we don’t know that for certain,” Dr. Peled said.
 

The argument for NRP

Nader Moazami, MD, professor of cardiovascular surgery, NYU Langone Health, New York, is one of the more vocal proponents of NRP for DCD heart transplantation in the United States, and has coauthored responses to these ethical concerns.

“People are confusing many issues to produce an argument against NRP,” he said.

“Our position is that death has already been declared based on the lack of circulatory function for over 5 minutes and this has been with the full agreement of the family, knowing that the patient has no chance of a meaningful life. No one is thinking of trying to resuscitate the patient. It has already been established that any future efforts to resuscitate are futile. In this case, we are not resuscitating the patient by restarting the circulation. It is just regional perfusion of the organs.”

Dr. Moazami pointed out this concept was accepted for the practice of abdominal DCD when it first started in the United States in the 1990s where cold perfusion was used to preserve the abdominal organs before they were retrieved from the body.

“The new approach of using NRP is similar except that it involves circulating warm blood, which will preserve organs better and result in higher quality organs for the recipient.”

On the issue of concern about possible circulation to the brain, Dr. Moazami said: “The ethical critics of NRP are questioning whether the brain may not be dead. We are arguing that the patient has already been declared dead as they have had a circulatory death. You cannot die twice.”

He maintained that the clamping of the arch vessels to the head will ensure that when the circulation is restarted “the natural process of circulatory death leading to brain death will continue to progress.” 

On the concerns about possible collateral flow to the brain, Dr. Moazami said there is no evidence that this occurs. “Prominent neurologists have said it is impossible for collaterals to provide any meaningful blood flow to the brain in this situation. And even if there is small amount of blood flow to the brain, this would be insufficient to maintain any meaningful brain function.”

But Dr. Peled argues that this has not been proved. “Even though we don’t think there is enough circulation to the brain for any function with NRP, we don’t know that with 100% certainty,” he said. “In my view, if there is a possibility of even the smallest amount of brain flow, we are going against the dead donor rule. We are rewriting the rules of death.”

Dr. Moazami countered: “Nothing in life is 100%, particularly in medicine. With that argument can you also prove with 100% certainty to me that there is absolutely no brain function with regular direct procurement DCD?  We know that brain death has started, but the question is: Has it been completed? We don’t know the answer to this question with 100% certainty, but that is the case for regular direct procurement DCD as well, and that has been accepted by almost everyone.

“The whole issue revolves around when are we comfortable that death has occurred,” he said. “Those against NRP are concerned that organs are being taken before the patient is dead. But the key point is that the patient has already been declared dead.”

Since there is some concern over the ethics of NRP, why not just stick to DCD with direct procurement?

Dr. Moazami argued that NRP results in healthier organs. “NRP allows more successful heart transplants, liver transplants, lung transplants. It preserves all the organs better,” he said. “This will have a big impact on recipients – they would obviously much prefer a healthier organ. In addition, the process is easier and cheaper, so more centers will be able to do it, therefore more transplants will get done and more lives will be saved if NRP is used.”

He added: “I am a physician taking care of sick patients. I believe I have to respect the wishes of the donor and the donor family; make sure I’m not doing any harm to the donor; and ensure the best quality possible of the organ I am retrieving to best serve the recipient. I am happy I am doing this by using NRP for DCD heart transplantation.”

But Dr. Peled argued that while NRP may have some possible advantages over direct procurement, that does not justify allowing a process to go ahead that is unethical.

“The fact that NRP may result in some benefits doesn’t justify violating the dead donor rule or the possibility, however small, of causing pain to the donor. If it’s unethical, it’s unethical. Full stop,” he said.

“I feel that NRP is not respecting the rights of our patients and that the process does not have adequate transparency. We took it to our local ethics committee, and they decided not to approve NRP in our health care system. I agree with this decision,” Dr. Peled said.  

“The trouble is different experts and different countries are not in agreement about this,” he added. “Reasonable, well-informed people are in disagreement. I do not believe we can have a standard of care where there is not consensus.”
 

Cautious nod

In a 2022 consensus statement, the International Society for Heart and Lung Transplantation (ISHLT) gave a cautious nod toward DCD and NRP, dependent on local recommendations.

The ISHLT conclusion reads: “With appropriate consideration of the ethical principles involved in organ donation, DCD can be undertaken in a morally permissible manner. In all cases, the introduction of DCD programs should be in accordance with local legal regulations. Countries lacking a DCD pathway should be encouraged to develop national ethical, professional, and legal frameworks to address both public and professional concerns.”

The author of a recent editorial on the subject, Ulrich P. Jorde, MD, head of the heart transplant program at Montefiore Medical Center, New York, said, “DCD is a great step forward. People regularly die on the heart transplant waiting list. DCD will increase the supply of donor hearts by 20% to 30%.”

However, he noted that while most societies have agreed on a protocol for organ donation based on brain death, the situation is more complicated with circulatory death.

“Different countries have different definitions of circulatory death. How long do we have to wait after the heart has stopped beating before the patient is declared dead? Most countries have agreed on 5 minutes, but other countries have imposed different periods and as such, different definitions of death.

“The ISHLT statement says that restarting the circulation is acceptable if death has been certified according to prevailing law and surgical interventions are undertaken to preclude any restoration of cerebral circulation. But our problem is that different regional societies have different definitions of circulatory, death which makes the situation confusing.”

Dr. Jorde added: “We also have to weigh the wishes of the donor and their family. If family, advocating what are presumed to be the donor’s wishes, have decided that DCD would be acceptable and they understand the concept and wish to donate the organs after circulatory death, this should be strongly considered under the concept of self-determination, a basic human right.”
 

Variations in practice around the world 

This ethical debate has led to large variations in practice around the world, with some countries, such as Spain, allowing both methods of DCD, while Australia allows direct procurement but not NRP, and Germany currently does not allow DCD at all.

In the United States, things are even more complicated, with some states allowing NRP while others don’t. Even within states, some hospitals and transplant organizations allow NRP, and others don’t. 

David A. D’Alessandro, MD, cardiac surgeon at Massachusetts General Hospital, Boston, uses only the direct procurement approach as his region does not allow NRP.

“The direct procurement approach is not controversial and to me that’s a big advantage. I believe we need to agree on the ethics first, and then get into a debate about which technique is better,” he told this news organization.

Dr. D’Alessandro and his group recently published the results of their study, with direct procurement DCD heart transplantation showing similar short-term clinical outcomes to DBD.

“We are only doing direct procurement and we are seeing good results that appear to be comparable to DBD. That is good enough for me,” he said.

Dr. D’Alessandro estimates that in the United States both types of DCD procedures are currently being done about equally.

“Anything we can do to increase the amount of hearts available for transplantation is a big deal,” he said. “At the moment, only the very sickest patients get a heart transplant, and many patients die on the transplant waiting list. Very sadly, many young people die every year from a circulatory death after having life support withdrawn. Before DCD, these beautiful functional organs were not able to be used. Now we have a way of saving lives with these organs.”

Dr. D’Alessandro noted that more and more centers in the United States are starting to perform DCD heart transplants. 

“Not every transplant center may join in as the DCD procedures are very resource-intensive and time-consuming. For low-volume transplant centers, it may not be worth the expense and anguish to do DCD heart transplants. But bigger centers will need to engage in DCD to remain competitive. My guess is that 50%-70% of U.S. transplant centers will do DCD in future.”

He said he thinks it is a “medical shortcoming” that agreement cannot be reached on the ethics of NRP. “In an ideal world everyone would be on the same page. It makes me a bit uncomfortable that some people think it’s okay and some people don’t.”

Adam DeVore, MD, a cardiologist at Duke University Medical Center, Durham, N.C., the first U.S. center to perform an adult DCD heart transplant, reported that his institution uses both methods, with the choice sometimes depending on how far the heart must travel.

“If the recipient is near, NRP may be chosen as the heart is transported on ice, but if it needs to go further away we are more likely to choose direct procurement and use of the OCS box,” he said. 

“I am really proud of what we’ve been able to do, helping to introduce DCD in the U.S.,” Dr. DeVore said. “This is having a massive benefit in increasing the number of hearts for donation with great outcomes.”  

But he acknowledged that the whole concept of DCD is somewhat controversial.  

“The idea of brain death really came about for the purpose of heart donation. The two things are very intricately tied. Trying to do heart donation without brain death having been declared is foreign to people. Also, in DCD there is the issue of [this]: When life support is removed, how long do we wait before death can be declared? That could be in conflict with how long the organ needs to remain viable. We are going through the process now of looking at these questions. There is a lot of variation in the U.S. about the withdrawal of care and the declaration of death, which is not completely standardized.

“But the concept of circulatory death itself is accepted after the withdrawal of life support. I think it’s the rush to take the organs out that makes it more difficult.”

Dr. DeVore said the field is moving forward now. “As the process has become more common, people have become more comfortable, probably because of the big difference it will make to saving lives. But we do need to try and standardize best practices.”

A recent Canadian review of the ethics of DCD concluded that the direct procurement approach would be in alignment with current medical guidelines, but that further work is required to evaluate the consistency of NRP with current Canadian death determination policy and to ensure the absence of brain perfusion during this process.

In the United Kingdom, the definition of death is brain-based, and brain death is defined on a neurological basis.

Dr. Stephen Large from Papworth explained that this recognizes the presence of brain-stem death through brain stem reflex testing after the withdrawal of life support, cardiorespiratory arrest and 5 further minutes of ischemia. As long as NRP does not restore intracranial (brainstem) perfusion after death has been confirmed, then it is consistent with laws for death determination and therefore both direct procurement and NRP are permissible.

However, the question over possible collateral flow to the brain has led the United Kingdom to pause the NRP technique as routine practice while this is investigated further. So, at the present time, the vast majority of DCD heart transplants are being conducted using the direct procurement approach.

But the United Kingdom is facing the bigger challenge: national funding that will soon end. “The DCD program in the U.K. has been extremely successful, increasing heart transplant rates by up to 28%,” Dr. Berman said. “Everybody wants it to continue. But at present the DCD program only has national funding in the U.K. until March 2023. We don’t know what will happen after that.”

The current model in the United Kingdom consists of three specialized DCD heart retrieval teams, a national protocol of direct organ procurement and delivery of DCD hearts to all seven transplant programs, both adult and pediatric.

If the national funding is not extended, “we will go back to individual hospitals trying to fund their own programs. That will be a serious threat to the program and could result in a large reduction in heart transplants,” said Dr. Berman.
 

Definition of death  

The crux of the issue with regard to NRP seems to be variations in how death is defined and the interpretation of those definitions.  

DCD donors will have had many tests indicating severe brain damage, a neurologist will have declared the prognosis is futile, and relatives will have agreed to withdraw life support, Dr. Jorde said. “The heart stops beating, and the stand-off time means that blood flow to the brain ceases completely for at least 5 minutes before circulatory death is declared. This is enough on its own to stop brain function.”

Dr. Large made the point that by the time the circulation is reestablished with NRP, more time has elapsed, and the brain will have been without perfusion for much longer than 5 minutes, so it would be “physiologically almost impossible” for there to be any blood flow to the brain.

“Because these brains are already very damaged before life support was removed, the intracranial pressure is high, which will further discourage blood flow to the brain,” he said. Then the donor goes through a period of anoxic heart arrest, up to 16 minutes at a minimum of no blood supply, enough on its own to stop meaningful brain function. 

“It’s asking an awful lot to believe that there might be any brain function left,” he said. “And if, on reestablishing the circulation with NRP, there is any blood in the collaterals, the pressure of such flow is so low it won’t enter the brain.”

Dr. Large also pointed out that the fact that the United Kingdom requires a neurologic definition for brain-stem death makes the process easier. 

In Australia, St. Vincent’s cardiologist Dr. MacDonald noted that death is defined as the irreversible cessation of circulation, so the NRP procedure is not allowed.

“With NRP, there is an ethical dilemma over whether the patient has legally died or not. Different countries have different ways of defining death. Perhaps society will have to review of the definition of death,” he suggested. Death is a process, “but for organ donation, we have to choose a moment in time of that process that satisfies everyone – when there is no prospect of recovery of the donor but the organs can still be utilized without harming the donor.” 

Dr. MacDonald said the field is in transition. “I don’t want to argue that one technique is better than the other; I think it’s good to have access to both techniques. Anything that will increase the number of transplants we can do is a good thing.”
 

Collaborative decision

Everyone seems to agree that there should be an effort to try to define death in a uniform way worldwide, and that international, national and local regulations are aligned with each other.

Dr. Jorde said: “It is of critical importance that local guidelines are streamlined, firstly in any one given country and then globally, and these things must be discussed transparently within society with all stakeholders – doctors, patients, citizens.”

Dr. Peled, from Providence St. Jude in California, concurred: “There is the possibility that we could change the definition of death, but that cannot be a decision based solely on transplant organizations. It has to be a collaborative decision with a large input from groups who do not have an interest in the procurement of organs.”

He added: “The dialogue so far has been civil, and everybody is trying to do the right thing. My hope is that as a civilized society we will figure out a way forward. At present, there is significant controversy about NRP, and families need to know that. My main concern is that if there is any lack of transparency in getting informed consent, then this risks people losing trust in the donation system.” 

Dr. Moazami, from NYU Langone, said the controversy has cast a cloud over the practice of NRP throughout the world. “We need to get it sorted out.”

He said he believes the way forward is to settle the question of whether there is any meaningful blood flow to the brain with the NRP technique.

“This is where the research has to focus. I believe this concern is hypothetical, but I am happy to do the studies to confirm that. Then, the issue should come to a rest. I think that is the right way forward – to do the studies rather than enforcing a moratorium on the practice because of a hypothetical concern.”

These studies on blood flow to the brain are now getting started in both the United Kingdom and the United States.

The U.K. study is being run by Antonio Rubino, MD, consultant in cardiothoracic anesthesia and intensive care at Papworth Hospital NHS Foundation and clinical lead, organ donation. Dr. Rubino explained that the study will assess cerebral blood flow using CT angiography of the brain. “We hypothesize that this will provide evidence to indicate that brain blood flow is not present during NRP and promote trust in the use of NRP in routine practice,” he said.

Dr. Large said: “Rather than having these tortured arguments, we will do the measurements. For the sake of society in this situation, I think it’s good to stop and take a breath. We must measure this, and we are doing just that.”

If there is any blood flow at all, Dr. Large said they will then have to seek expert guidance. “Say we find there is 50 mL of blood flow and normal blood flow is 1,500 mL/min. We will need expert guidance on whether it is remotely possible to be sentient on that. I would say it would be extraordinarily unlikely.”  

Dr. Berman summarized the situation: “DCD is increasing the availability of hearts for transplant. This is saving lives, reducing the number of patients on the waiting list, and reducing hospital stays for patients unable to leave the hospital without a transplant. It is definitely here to stay. It is crucial that it gets funded properly, and it is also crucial that we resolve the NRP ethical issues as soon as possible.”

He is hopeful that some of these issues will be resolved this year.

Dr. MacDonald reported he has received “in-kind” support from Transmedics through provision of research modules for preclinical research studies. Dr. D’Alessandro reported he is on the speakers bureau for Abiomed, not relevant to this article. No other relevant disclosures were reported.
 

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

WASHINGTON – Left atrial appendage closure can be performed safely and effectively in older patients, those with end-stage renal disease, and likely others not included in the pivotal clinical trials, according to a series of new studies, including a late-breaker, presented on the both older and newer Watchman devices at the Cardiovascular Research Technologies conference.

In the case of the late-breaking clinical trial report, which included more than 60,000 patients, the goal was to look at the safety of the Watchman FLX, which is the newest of the devices in real-world practice, according to Samir R. Kapadia, MD, chairman of the department of cardiovascular medicine at the Cleveland Clinic.

Ted Bosworth/MDedge News

In the SURPASS registry, the number of patients discharged on the Watchman FLX climbed from zero in August 2020, when data accrual began, to 66,894 by March 2022. For the current analysis, 45-day follow-up was available for 61,963 patients and 1-year follow-up was available for 18,233.

Based on this number of patients treated by more than 2,300 clinicians at more than 740 sites, the SURPASS registry establishes that Watchman FLX “can be accomplished safely with clinical outcomes similar to pivotal trials at 45 days and 1 year,” Dr. Kapadia reported.
 

No surprises found in real-world outcome

At 7 days or hospital discharge (whichever came last), the rate of all-cause death was 0.18%, the rate of ischemic stroke was 0.13%, and there were no systemic emboli. By 45 days, the rate of all-cause death (0.84%) and stroke of any kind (0.32%) remained less than 1% and there were still no systemic emboli. Major bleeding events, of which about one-third occurred during hospitalization, had reached 3.34% by day 45.

By 1 year, all-cause mortality had risen to 8.3%, the stroke rate was 1.6%, and major bleeding reached 6.7%. The rate of systemic emboli remained very low (0.1%). The rates of death and stroke rose at a slow but steady rate throughout the 1-year follow-up. In contrast, major bleeding events rose steeply in the first 90 days and were followed by a much slower accrual subsequently.

At 1 year, 84.4% of patients had a complete seal. Leaks ≤ 3 mm were observed in 12.1%. The remaining leaks were larger, but just 0.7% had a leak > 5 mm.

Relative to the first-generation Watchman, the Watchman FLX has numerous design changes, including a shorter profile, more struts, and a reduced metal exposure. Most of these changes were performed to make the device easier to deploy.

When the SURPASS data are compared to the pivotal trials with Watchman FLX or to the Ewolution and National Cardiovascular Data (NCD) registries, which were created to monitor efficacy and safety with the earlier generation Watchman, the outcomes are similar or, in many cases, numerically favorable for such outcomes as bleeding and rates of stroke.

In addition to providing reassurance for the real-world safety of Watchman FLX, Dr. Kapadia said that these data establish reasonable benchmarks for centers tracking in-hospital and 1-year outcomes.

Dr. Kapadia also reported that outcomes overall in SURPASS were similar in women and men with the exception of major bleeding, a finding common to other interventional studies.

The late-breaker panelists generally agreed that SURPASS provides a robust set of data by which to be reassured, but David J. Cohen, MD, director of Clinical and Outcomes Research at the Cardiovascular Research Foundation in New York, said that he thinks the rate of bleeding is unnecessarily high.

“You really need to figure out a way to get the rate of bleeding at 45 days down,” Dr. Cohen said. He called for studies of anticoagulation in the post-procedural period that offer a better benefit-to-risk ratio.
 

Elderly patients benefit equally from Watchman

Yet, Watchman devices are generally regarded as a success story, and this has led investigators to evaluate safety in patients not well represented or explicitly excluded from clinical trials, such as the elderly and those with end-stage renal disease (ESRD). New data derived from experience in both of these groups were presented at the conference, which was sponsored by MedStar Heart & Vascular Institute.

To tease out the relative safety of Watchman in octogenarians, Samian Sulaiman, MD, a cardiology fellow at West Virginia University Heart and Vascular Institute, Morgantown, performed a competing risk analysis to study the relative benefit of Watchman devices after controlling for the greater overall risk of complications in the elderly.

In raw data comparisons of those 80 years of age or older to those younger in published trials, the not-surprising result is that overall rates of death and ischemic events are far higher in the elderly, according to Dr. Sulaiman, but it’s an “unfair comparison,” he said.

“It is easy to mistakenly conclude that left atrial appendage closure is associated with worse outcomes, but older patients have far higher rates of these events independent of other factors,” Dr. Sulaiman noted.

In fact, in his comparison of 472 older patients to 1,404 younger patients, the seal rates at 45 days, 6 months, and 12 months are almost identical. Moreover, after the extensive adjustments performed for competing risk analysis, the rates of death, stroke, and bleeding were also almost identical for those 80 years or older whether or not they received a Watchman.

Although he acknowledged the risk for residual confounding, Dr. Sulaiman concluded that elderly patients derive about the same benefits as younger patients from the Watchman. He concluded age alone should not be a factor in selecting candidates for this device.
 

ESRD is not Watchman contraindication

A similar point was made about ESRD based on analysis of 237 patients who received either an earlier generation Watchman or the Watchman FLX. Initiated in Spain, the study was amended to collect data from centers elsewhere in Europe, the United States, and Australia.

Successful implantation was achieved in 99.2% of the patients, reported Armando Perez de Prado, MD, PhD, head of interventional cardiology at the University of Leon, Spain.

Ted Bosworth/MDedge News

WASHINGTON – Left atrial appendage closure can be performed safely and effectively in older patients, those with end-stage renal disease, and likely others not included in the pivotal clinical trials, according to a series of new studies, including a late-breaker, presented on the both older and newer Watchman devices at the Cardiovascular Research Technologies conference.

In the case of the late-breaking clinical trial report, which included more than 60,000 patients, the goal was to look at the safety of the Watchman FLX, which is the newest of the devices in real-world practice, according to Samir R. Kapadia, MD, chairman of the department of cardiovascular medicine at the Cleveland Clinic.

Ted Bosworth/MDedge News

In the SURPASS registry, the number of patients discharged on the Watchman FLX climbed from zero in August 2020, when data accrual began, to 66,894 by March 2022. For the current analysis, 45-day follow-up was available for 61,963 patients and 1-year follow-up was available for 18,233.

Based on this number of patients treated by more than 2,300 clinicians at more than 740 sites, the SURPASS registry establishes that Watchman FLX “can be accomplished safely with clinical outcomes similar to pivotal trials at 45 days and 1 year,” Dr. Kapadia reported.
 

No surprises found in real-world outcome

At 7 days or hospital discharge (whichever came last), the rate of all-cause death was 0.18%, the rate of ischemic stroke was 0.13%, and there were no systemic emboli. By 45 days, the rate of all-cause death (0.84%) and stroke of any kind (0.32%) remained less than 1% and there were still no systemic emboli. Major bleeding events, of which about one-third occurred during hospitalization, had reached 3.34% by day 45.

By 1 year, all-cause mortality had risen to 8.3%, the stroke rate was 1.6%, and major bleeding reached 6.7%. The rate of systemic emboli remained very low (0.1%). The rates of death and stroke rose at a slow but steady rate throughout the 1-year follow-up. In contrast, major bleeding events rose steeply in the first 90 days and were followed by a much slower accrual subsequently.

At 1 year, 84.4% of patients had a complete seal. Leaks ≤ 3 mm were observed in 12.1%. The remaining leaks were larger, but just 0.7% had a leak > 5 mm.

Relative to the first-generation Watchman, the Watchman FLX has numerous design changes, including a shorter profile, more struts, and a reduced metal exposure. Most of these changes were performed to make the device easier to deploy.

When the SURPASS data are compared to the pivotal trials with Watchman FLX or to the Ewolution and National Cardiovascular Data (NCD) registries, which were created to monitor efficacy and safety with the earlier generation Watchman, the outcomes are similar or, in many cases, numerically favorable for such outcomes as bleeding and rates of stroke.

In addition to providing reassurance for the real-world safety of Watchman FLX, Dr. Kapadia said that these data establish reasonable benchmarks for centers tracking in-hospital and 1-year outcomes.

Dr. Kapadia also reported that outcomes overall in SURPASS were similar in women and men with the exception of major bleeding, a finding common to other interventional studies.

The late-breaker panelists generally agreed that SURPASS provides a robust set of data by which to be reassured, but David J. Cohen, MD, director of Clinical and Outcomes Research at the Cardiovascular Research Foundation in New York, said that he thinks the rate of bleeding is unnecessarily high.

“You really need to figure out a way to get the rate of bleeding at 45 days down,” Dr. Cohen said. He called for studies of anticoagulation in the post-procedural period that offer a better benefit-to-risk ratio.
 

Elderly patients benefit equally from Watchman

Yet, Watchman devices are generally regarded as a success story, and this has led investigators to evaluate safety in patients not well represented or explicitly excluded from clinical trials, such as the elderly and those with end-stage renal disease (ESRD). New data derived from experience in both of these groups were presented at the conference, which was sponsored by MedStar Heart & Vascular Institute.

To tease out the relative safety of Watchman in octogenarians, Samian Sulaiman, MD, a cardiology fellow at West Virginia University Heart and Vascular Institute, Morgantown, performed a competing risk analysis to study the relative benefit of Watchman devices after controlling for the greater overall risk of complications in the elderly.

In raw data comparisons of those 80 years of age or older to those younger in published trials, the not-surprising result is that overall rates of death and ischemic events are far higher in the elderly, according to Dr. Sulaiman, but it’s an “unfair comparison,” he said.

“It is easy to mistakenly conclude that left atrial appendage closure is associated with worse outcomes, but older patients have far higher rates of these events independent of other factors,” Dr. Sulaiman noted.

In fact, in his comparison of 472 older patients to 1,404 younger patients, the seal rates at 45 days, 6 months, and 12 months are almost identical. Moreover, after the extensive adjustments performed for competing risk analysis, the rates of death, stroke, and bleeding were also almost identical for those 80 years or older whether or not they received a Watchman.

Although he acknowledged the risk for residual confounding, Dr. Sulaiman concluded that elderly patients derive about the same benefits as younger patients from the Watchman. He concluded age alone should not be a factor in selecting candidates for this device.
 

ESRD is not Watchman contraindication

A similar point was made about ESRD based on analysis of 237 patients who received either an earlier generation Watchman or the Watchman FLX. Initiated in Spain, the study was amended to collect data from centers elsewhere in Europe, the United States, and Australia.

Successful implantation was achieved in 99.2% of the patients, reported Armando Perez de Prado, MD, PhD, head of interventional cardiology at the University of Leon, Spain.

Ted Bosworth/MDedge News

WASHINGTON – Left atrial appendage closure can be performed safely and effectively in older patients, those with end-stage renal disease, and likely others not included in the pivotal clinical trials, according to a series of new studies, including a late-breaker, presented on the both older and newer Watchman devices at the Cardiovascular Research Technologies conference.

In the case of the late-breaking clinical trial report, which included more than 60,000 patients, the goal was to look at the safety of the Watchman FLX, which is the newest of the devices in real-world practice, according to Samir R. Kapadia, MD, chairman of the department of cardiovascular medicine at the Cleveland Clinic.

Ted Bosworth/MDedge News

In the SURPASS registry, the number of patients discharged on the Watchman FLX climbed from zero in August 2020, when data accrual began, to 66,894 by March 2022. For the current analysis, 45-day follow-up was available for 61,963 patients and 1-year follow-up was available for 18,233.

Based on this number of patients treated by more than 2,300 clinicians at more than 740 sites, the SURPASS registry establishes that Watchman FLX “can be accomplished safely with clinical outcomes similar to pivotal trials at 45 days and 1 year,” Dr. Kapadia reported.
 

No surprises found in real-world outcome

At 7 days or hospital discharge (whichever came last), the rate of all-cause death was 0.18%, the rate of ischemic stroke was 0.13%, and there were no systemic emboli. By 45 days, the rate of all-cause death (0.84%) and stroke of any kind (0.32%) remained less than 1% and there were still no systemic emboli. Major bleeding events, of which about one-third occurred during hospitalization, had reached 3.34% by day 45.

By 1 year, all-cause mortality had risen to 8.3%, the stroke rate was 1.6%, and major bleeding reached 6.7%. The rate of systemic emboli remained very low (0.1%). The rates of death and stroke rose at a slow but steady rate throughout the 1-year follow-up. In contrast, major bleeding events rose steeply in the first 90 days and were followed by a much slower accrual subsequently.

At 1 year, 84.4% of patients had a complete seal. Leaks ≤ 3 mm were observed in 12.1%. The remaining leaks were larger, but just 0.7% had a leak > 5 mm.

Relative to the first-generation Watchman, the Watchman FLX has numerous design changes, including a shorter profile, more struts, and a reduced metal exposure. Most of these changes were performed to make the device easier to deploy.

When the SURPASS data are compared to the pivotal trials with Watchman FLX or to the Ewolution and National Cardiovascular Data (NCD) registries, which were created to monitor efficacy and safety with the earlier generation Watchman, the outcomes are similar or, in many cases, numerically favorable for such outcomes as bleeding and rates of stroke.

In addition to providing reassurance for the real-world safety of Watchman FLX, Dr. Kapadia said that these data establish reasonable benchmarks for centers tracking in-hospital and 1-year outcomes.

Dr. Kapadia also reported that outcomes overall in SURPASS were similar in women and men with the exception of major bleeding, a finding common to other interventional studies.

The late-breaker panelists generally agreed that SURPASS provides a robust set of data by which to be reassured, but David J. Cohen, MD, director of Clinical and Outcomes Research at the Cardiovascular Research Foundation in New York, said that he thinks the rate of bleeding is unnecessarily high.

“You really need to figure out a way to get the rate of bleeding at 45 days down,” Dr. Cohen said. He called for studies of anticoagulation in the post-procedural period that offer a better benefit-to-risk ratio.
 

Elderly patients benefit equally from Watchman

Yet, Watchman devices are generally regarded as a success story, and this has led investigators to evaluate safety in patients not well represented or explicitly excluded from clinical trials, such as the elderly and those with end-stage renal disease (ESRD). New data derived from experience in both of these groups were presented at the conference, which was sponsored by MedStar Heart & Vascular Institute.

To tease out the relative safety of Watchman in octogenarians, Samian Sulaiman, MD, a cardiology fellow at West Virginia University Heart and Vascular Institute, Morgantown, performed a competing risk analysis to study the relative benefit of Watchman devices after controlling for the greater overall risk of complications in the elderly.

In raw data comparisons of those 80 years of age or older to those younger in published trials, the not-surprising result is that overall rates of death and ischemic events are far higher in the elderly, according to Dr. Sulaiman, but it’s an “unfair comparison,” he said.

“It is easy to mistakenly conclude that left atrial appendage closure is associated with worse outcomes, but older patients have far higher rates of these events independent of other factors,” Dr. Sulaiman noted.

In fact, in his comparison of 472 older patients to 1,404 younger patients, the seal rates at 45 days, 6 months, and 12 months are almost identical. Moreover, after the extensive adjustments performed for competing risk analysis, the rates of death, stroke, and bleeding were also almost identical for those 80 years or older whether or not they received a Watchman.

Although he acknowledged the risk for residual confounding, Dr. Sulaiman concluded that elderly patients derive about the same benefits as younger patients from the Watchman. He concluded age alone should not be a factor in selecting candidates for this device.
 

ESRD is not Watchman contraindication

A similar point was made about ESRD based on analysis of 237 patients who received either an earlier generation Watchman or the Watchman FLX. Initiated in Spain, the study was amended to collect data from centers elsewhere in Europe, the United States, and Australia.

Successful implantation was achieved in 99.2% of the patients, reported Armando Perez de Prado, MD, PhD, head of interventional cardiology at the University of Leon, Spain.

Ted Bosworth/MDedge News