Bruce Jancin

Transcatheter replacement of a failing surgical bioprosthetic valve showed durably favorable valve hemodynamics coupled with markedly improved patient functional status and excellent quality of life benefits at 5 years of follow-up in the prospective multicenter PARTNER 2 ViV Registry, Rebecca T. Hahn, MD, reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

She provided an update on previously reported 3-year outcomes in 365 patients at high to extreme surgical risk who underwent transcatheter aortic valve replacement (TAVR) with a 23-mm or 26-mm Sapien XT valve to address a failing surgical aortic bioprosthesis. The ViV (valve-in-valve) results are quite encouraging, she said at the meeting sponsored by the Cardiovascular Research Foundation.

“I think that this information is changing our algorithm for how we initially make treatment decisions in our patients,” according to the cardiologist.

“We now know that we can salvage a surgical bioprosthetic valve failure with a transcatheter procedure that is relatively safe and has good outcomes out to 5 years – and that’s with a second-generation TAVR valve, not even the third-generation valve,” observed Dr. Hahn, director of interventional echocardiography at New York–Presbyterian/Columbia University Medical Center and professor of clinical medicine at Columbia University, both in New York.

Interventionalists consider the third-generation valve, the Sapien 3, a superior platform compared to the Sapien 2 in use when the PARTNERS 2 ViV Registry started, she added.

At 5 years of follow-up since TAVR valve implantation, the all-cause mortality rate was 50.6%, up significantly from 32.7% at 3 years. However, this high mortality comes as no surprise given that registry participants had a profound comorbidity burden, as reflected in their mean Society of Thoracic Surgeons risk score of 9.1% at the time of TAVR. Of note, the 5-year mortality in surgically high- to extreme-risk patients in the ViV registry was comparable with the 45.9% rate at 5 years following TAVR of a native valve in intermediate-risk patients in the PARTNER 2b trial and superior to the 73% rate with TAVR of a native aortic valve in inoperable patients in PARTNER 2a, the cardiologist said.

The 5-year stroke rate in the ViV registry was 10.1%, up from 6.2% at 3 years. The cumulative incidence of death or stroke through 5 years was 53.8%.

Mortality was significantly lower in recipients of a 26-mm Sapien 2 valve than with the 23-mm version, at 40% at 5 years versus 53%. Recipients of the smaller valve were more often male, had a higher prevalence of coronary artery disease, a higher surgical risk score, a significantly smaller baseline aortic valve area, and a higher mean gradient. Dr. Hahn and her coinvestigators are now examining their data to determine if surgical valve size/patient mismatch was a major driver of adverse outcomes, as has been reported in some other datasets.

At 5 years, the rate of structural valve deterioration–related hemodynamic valve deterioration (SVD-HVD) or bioprosthetic valve failure (BVF) using the soon-to-be-published Valve Academic Research Consortium–3 definitions was 6.6%. The rates of each class of valve deterioration at 5 years in this high- to extreme-risk population were 1.2 per 100 patient-years for SVD-HVD, 0.88 per 100 patient-years for all BVF, and 0.4 per 100 patient-years for SVD-related BVF.

Fully 51% of 5-year survivors were NYHA functional class I, whereas more than 90% of patients were class III or IV at baseline. The mean gradient was 16.8 mm Hg at 5 years, the Doppler velocity index was 0.35, and the mean Kansas City Cardiomyopathy Questionnaire overall summary score was 74.2, all closely similar to the values at 3 years. That dramatic and sustained improvement in the Kansas City Cardiomyopathy Questionnaire from a baseline of 43.1 points is larger than ever seen in any clinical trial of native valve TAVR, Dr. Hahn noted.

For discussant Vinayak N. Bapat, MD a cardiothoracic surgeon at the Minneapolis Heart Institute Foundation, the 5-year PARTNER 2 follow-up data contains a clear take-home message: “These data show that, when we as surgeons are putting in small valves, we ought to put in valves that are expandable.”

Discussant Jeroen J. Bax, MD, had one major caveat regarding the PARTNER 2 ViV Registry findings: They focused on high-surgical-risk patients.

“I think we would all agree that in high-risk patients, valve-in-valve is a better option than redo surgery. But in young, low-risk patients who are getting a bioprosthetic valve – and we’re going to be seeing more and more of them because over 90% of patients in Europe getting aortic valve surgery now are getting a bioprosthetic valve – we really don’t know what the best option is,” said Dr. Bax, professor of cardiology at the University of Leiden (the Netherlands).

He suggested a randomized trial of TAVR versus redo surgery in low-risk patients with failing bioprosthetic valves is in order, particularly in light of concerns raised by a recent report from a French national patient registry. These were “high-quality, real-world data,” Dr. Bax said, and while they showed better early outcomes for TAVR ViV than with redo surgery, there was a crossing of the curves for heart failure hospitalization already by 2 years.

“We need to look closely at younger, low-risk patients,” he concluded.

The PARTNER 2 ViV Registry is funded by Edwards Lifesciences. Dr. Hahn reported receiving research support from Philips Healthcare and 3Mensio and honoraria from Boston Scientific, Edwards Lifesciences, and Philips Healthcare.

[email protected]

SOURCE: Hahn RT. TCT 2020, Late breaker.

Transcatheter replacement of a failing surgical bioprosthetic valve showed durably favorable valve hemodynamics coupled with markedly improved patient functional status and excellent quality of life benefits at 5 years of follow-up in the prospective multicenter PARTNER 2 ViV Registry, Rebecca T. Hahn, MD, reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

She provided an update on previously reported 3-year outcomes in 365 patients at high to extreme surgical risk who underwent transcatheter aortic valve replacement (TAVR) with a 23-mm or 26-mm Sapien XT valve to address a failing surgical aortic bioprosthesis. The ViV (valve-in-valve) results are quite encouraging, she said at the meeting sponsored by the Cardiovascular Research Foundation.

“I think that this information is changing our algorithm for how we initially make treatment decisions in our patients,” according to the cardiologist.

“We now know that we can salvage a surgical bioprosthetic valve failure with a transcatheter procedure that is relatively safe and has good outcomes out to 5 years – and that’s with a second-generation TAVR valve, not even the third-generation valve,” observed Dr. Hahn, director of interventional echocardiography at New York–Presbyterian/Columbia University Medical Center and professor of clinical medicine at Columbia University, both in New York.

Interventionalists consider the third-generation valve, the Sapien 3, a superior platform compared to the Sapien 2 in use when the PARTNERS 2 ViV Registry started, she added.

At 5 years of follow-up since TAVR valve implantation, the all-cause mortality rate was 50.6%, up significantly from 32.7% at 3 years. However, this high mortality comes as no surprise given that registry participants had a profound comorbidity burden, as reflected in their mean Society of Thoracic Surgeons risk score of 9.1% at the time of TAVR. Of note, the 5-year mortality in surgically high- to extreme-risk patients in the ViV registry was comparable with the 45.9% rate at 5 years following TAVR of a native valve in intermediate-risk patients in the PARTNER 2b trial and superior to the 73% rate with TAVR of a native aortic valve in inoperable patients in PARTNER 2a, the cardiologist said.

The 5-year stroke rate in the ViV registry was 10.1%, up from 6.2% at 3 years. The cumulative incidence of death or stroke through 5 years was 53.8%.

Mortality was significantly lower in recipients of a 26-mm Sapien 2 valve than with the 23-mm version, at 40% at 5 years versus 53%. Recipients of the smaller valve were more often male, had a higher prevalence of coronary artery disease, a higher surgical risk score, a significantly smaller baseline aortic valve area, and a higher mean gradient. Dr. Hahn and her coinvestigators are now examining their data to determine if surgical valve size/patient mismatch was a major driver of adverse outcomes, as has been reported in some other datasets.

At 5 years, the rate of structural valve deterioration–related hemodynamic valve deterioration (SVD-HVD) or bioprosthetic valve failure (BVF) using the soon-to-be-published Valve Academic Research Consortium–3 definitions was 6.6%. The rates of each class of valve deterioration at 5 years in this high- to extreme-risk population were 1.2 per 100 patient-years for SVD-HVD, 0.88 per 100 patient-years for all BVF, and 0.4 per 100 patient-years for SVD-related BVF.

Fully 51% of 5-year survivors were NYHA functional class I, whereas more than 90% of patients were class III or IV at baseline. The mean gradient was 16.8 mm Hg at 5 years, the Doppler velocity index was 0.35, and the mean Kansas City Cardiomyopathy Questionnaire overall summary score was 74.2, all closely similar to the values at 3 years. That dramatic and sustained improvement in the Kansas City Cardiomyopathy Questionnaire from a baseline of 43.1 points is larger than ever seen in any clinical trial of native valve TAVR, Dr. Hahn noted.

For discussant Vinayak N. Bapat, MD a cardiothoracic surgeon at the Minneapolis Heart Institute Foundation, the 5-year PARTNER 2 follow-up data contains a clear take-home message: “These data show that, when we as surgeons are putting in small valves, we ought to put in valves that are expandable.”

Discussant Jeroen J. Bax, MD, had one major caveat regarding the PARTNER 2 ViV Registry findings: They focused on high-surgical-risk patients.

“I think we would all agree that in high-risk patients, valve-in-valve is a better option than redo surgery. But in young, low-risk patients who are getting a bioprosthetic valve – and we’re going to be seeing more and more of them because over 90% of patients in Europe getting aortic valve surgery now are getting a bioprosthetic valve – we really don’t know what the best option is,” said Dr. Bax, professor of cardiology at the University of Leiden (the Netherlands).

He suggested a randomized trial of TAVR versus redo surgery in low-risk patients with failing bioprosthetic valves is in order, particularly in light of concerns raised by a recent report from a French national patient registry. These were “high-quality, real-world data,” Dr. Bax said, and while they showed better early outcomes for TAVR ViV than with redo surgery, there was a crossing of the curves for heart failure hospitalization already by 2 years.

“We need to look closely at younger, low-risk patients,” he concluded.

The PARTNER 2 ViV Registry is funded by Edwards Lifesciences. Dr. Hahn reported receiving research support from Philips Healthcare and 3Mensio and honoraria from Boston Scientific, Edwards Lifesciences, and Philips Healthcare.

[email protected]

SOURCE: Hahn RT. TCT 2020, Late breaker.

Transcatheter replacement of a failing surgical bioprosthetic valve showed durably favorable valve hemodynamics coupled with markedly improved patient functional status and excellent quality of life benefits at 5 years of follow-up in the prospective multicenter PARTNER 2 ViV Registry, Rebecca T. Hahn, MD, reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

She provided an update on previously reported 3-year outcomes in 365 patients at high to extreme surgical risk who underwent transcatheter aortic valve replacement (TAVR) with a 23-mm or 26-mm Sapien XT valve to address a failing surgical aortic bioprosthesis. The ViV (valve-in-valve) results are quite encouraging, she said at the meeting sponsored by the Cardiovascular Research Foundation.

“I think that this information is changing our algorithm for how we initially make treatment decisions in our patients,” according to the cardiologist.

“We now know that we can salvage a surgical bioprosthetic valve failure with a transcatheter procedure that is relatively safe and has good outcomes out to 5 years – and that’s with a second-generation TAVR valve, not even the third-generation valve,” observed Dr. Hahn, director of interventional echocardiography at New York–Presbyterian/Columbia University Medical Center and professor of clinical medicine at Columbia University, both in New York.

Interventionalists consider the third-generation valve, the Sapien 3, a superior platform compared to the Sapien 2 in use when the PARTNERS 2 ViV Registry started, she added.

At 5 years of follow-up since TAVR valve implantation, the all-cause mortality rate was 50.6%, up significantly from 32.7% at 3 years. However, this high mortality comes as no surprise given that registry participants had a profound comorbidity burden, as reflected in their mean Society of Thoracic Surgeons risk score of 9.1% at the time of TAVR. Of note, the 5-year mortality in surgically high- to extreme-risk patients in the ViV registry was comparable with the 45.9% rate at 5 years following TAVR of a native valve in intermediate-risk patients in the PARTNER 2b trial and superior to the 73% rate with TAVR of a native aortic valve in inoperable patients in PARTNER 2a, the cardiologist said.

The 5-year stroke rate in the ViV registry was 10.1%, up from 6.2% at 3 years. The cumulative incidence of death or stroke through 5 years was 53.8%.

Mortality was significantly lower in recipients of a 26-mm Sapien 2 valve than with the 23-mm version, at 40% at 5 years versus 53%. Recipients of the smaller valve were more often male, had a higher prevalence of coronary artery disease, a higher surgical risk score, a significantly smaller baseline aortic valve area, and a higher mean gradient. Dr. Hahn and her coinvestigators are now examining their data to determine if surgical valve size/patient mismatch was a major driver of adverse outcomes, as has been reported in some other datasets.

At 5 years, the rate of structural valve deterioration–related hemodynamic valve deterioration (SVD-HVD) or bioprosthetic valve failure (BVF) using the soon-to-be-published Valve Academic Research Consortium–3 definitions was 6.6%. The rates of each class of valve deterioration at 5 years in this high- to extreme-risk population were 1.2 per 100 patient-years for SVD-HVD, 0.88 per 100 patient-years for all BVF, and 0.4 per 100 patient-years for SVD-related BVF.

Fully 51% of 5-year survivors were NYHA functional class I, whereas more than 90% of patients were class III or IV at baseline. The mean gradient was 16.8 mm Hg at 5 years, the Doppler velocity index was 0.35, and the mean Kansas City Cardiomyopathy Questionnaire overall summary score was 74.2, all closely similar to the values at 3 years. That dramatic and sustained improvement in the Kansas City Cardiomyopathy Questionnaire from a baseline of 43.1 points is larger than ever seen in any clinical trial of native valve TAVR, Dr. Hahn noted.

For discussant Vinayak N. Bapat, MD a cardiothoracic surgeon at the Minneapolis Heart Institute Foundation, the 5-year PARTNER 2 follow-up data contains a clear take-home message: “These data show that, when we as surgeons are putting in small valves, we ought to put in valves that are expandable.”

Discussant Jeroen J. Bax, MD, had one major caveat regarding the PARTNER 2 ViV Registry findings: They focused on high-surgical-risk patients.

“I think we would all agree that in high-risk patients, valve-in-valve is a better option than redo surgery. But in young, low-risk patients who are getting a bioprosthetic valve – and we’re going to be seeing more and more of them because over 90% of patients in Europe getting aortic valve surgery now are getting a bioprosthetic valve – we really don’t know what the best option is,” said Dr. Bax, professor of cardiology at the University of Leiden (the Netherlands).

He suggested a randomized trial of TAVR versus redo surgery in low-risk patients with failing bioprosthetic valves is in order, particularly in light of concerns raised by a recent report from a French national patient registry. These were “high-quality, real-world data,” Dr. Bax said, and while they showed better early outcomes for TAVR ViV than with redo surgery, there was a crossing of the curves for heart failure hospitalization already by 2 years.

“We need to look closely at younger, low-risk patients,” he concluded.

The PARTNER 2 ViV Registry is funded by Edwards Lifesciences. Dr. Hahn reported receiving research support from Philips Healthcare and 3Mensio and honoraria from Boston Scientific, Edwards Lifesciences, and Philips Healthcare.

[email protected]

SOURCE: Hahn RT. TCT 2020, Late breaker.

European dermatologists shifted en masse to teledermatology during the first wave of the COVID-19 pandemic, and most of them disliked the videoconferencing experience intensely, according to the findings of a survey presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“The results of our survey clearly show 7 out of 10 participating dermatologists declared that they were not happy with teledermatology, and most of them declared that they were not at all happy,” according to Mariano Suppa, MD, PhD, of the department of dermatology and venereology, Free University of Brussels.

“It was very interesting: it was not just about the lack of a good quality of consultation, but was also related to some extent to a lack of respect from some patients, and also a lack of empathy. The majority of survey respondents felt [attacked] by their own patients because they were proposing teledermatology. So, yes, we were forced to go to teledermatology, and I think we will be again to some extent, but clearly we’re not happy about it,” he elaborated in response to a question from session chair Brigitte Dreno, MD, professor of dermatology and vice dean of the faculty of medicine at the University of Nantes (France).

The survey, conducted by the EADV communication committee, assessed the pandemic’s impact on European dermatologists’ professional practices and personal lives through 30 brief questions, with space at the end for additional open-ended comments. In the comments section, many dermatologists vented about their income loss, the disorganized response to round one of the pandemic, and most of all about teledermatology. Common complaints were that teledermatology required a huge consumption of energy and constituted a major intrusion upon the physicians’ personal lives. And then there was the common theme of unkind treatment by some patients.

The survey was sent twice in June 2020 to more than 4,800 EADV members. It was completed by 490 dermatologists from 39 countries. Dr. Suppa attributed the low response rate to physician weariness of the topic due to saturation news media coverage of the pandemic.

Sixty-nine percent of responding dermatologists were women. Fifty-two percent of participants were over age 50, 81% lived in a city, and 53% worked in a university or public hospital or clinic. Twelve percent lived alone.

Impact on professional practice

Many European dermatologists were on the front lines in dealing with the first wave of COVID-19. Twenty-eight percent worked in a COVID-19 unit. Forty-eight percent of dermatologists performed COVID-19 tests, and those who didn’t either had no patient contact or couldn’t get test kits. Thirty-five percent of dermatologists saw patients who presented with skin signs of COVID-19. Four percent of survey respondents became infected.

Seventy percent rescheduled or canceled all or most patient appointments. Clinical care was prioritized: during the peak of the pandemic, 76% of dermatologists saw only urgent cases – mostly potentially serious rashes – and dermato-oncology patients. Seventy-six percent of dermatologists performed teledermatology, although by June 60% of respondents reported seeing at least three-quarters of their patients face-to-face.

Twenty-three percent of dermatologists reported having lost most or all of their income during March through June, and another 26% lost about half.
 

Impact on dermatologists’ personal lives

About half of survey respondents reported feeling stressed, and a similar percentage checked the box marked ‘anxiety.’ Nine percent reported depressive symptoms, 15% mentioned feeling anger, 17% uselessness, and 2% admitted suicidal ideation. But 30% of dermatologists reported experiencing no negative psychological effects whatsoever stemming from the pandemic.

Sixteen percent of dermatologists reported drinking more alcohol during sequestration.

But respondents cited positive effects as well: a renewed appreciation of the importance of time, and enjoyment of the additional time spent with family and alone. Many dermatologists relished the opportunity to spend more time cooking, reading literature, doing research, listening to or playing music, and practicing yoga or meditation. And dermatologists took solace and pride in being members of the vital medical community.

Dr. Dreno asked if the survey revealed evidence of underdiagnosis and undertreatment of dermatologic diseases during the pandemic. Dr. Suppa replied that the survey didn’t address that issue, but it’s his personal opinion that this was no doubt the case. Roughly one-quarter of dermatologists canceled all appointments, and when dermatology clinics became filled beginning in June, he and his colleagues saw a number of cases of delayed-diagnosis advanced skin cancer.

“I think that the diseases that were really penalized were the chronic inflammatory diseases, such as psoriasis, hidradenitis suppurativa, and also atopic dermatitis. We were doing a lot of telephone consultations for those patients at that time, and we saw in June that for those particular patients there was an unmet need in the pandemic because some of them really needed to have been seen. I think this is a lesson we should learn for the second wave that we’re unfortunately facing right now: We need to adopt restrictive measures to avoid spreading the pandemic, yes, for sure, but we need to keep in mind that there is not just COVID-19, but also other important diseases,” Dr. Suppa said.

A second EADV survey will be performed during the fall/winter wave of the pandemic.

Dr. Suppa reported having no financial conflicts regarding the EADV-funded survey.
 

[email protected]

SOURCE: Suppa M. EADV 2020. Presentation D3T03.4D

European dermatologists shifted en masse to teledermatology during the first wave of the COVID-19 pandemic, and most of them disliked the videoconferencing experience intensely, according to the findings of a survey presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“The results of our survey clearly show 7 out of 10 participating dermatologists declared that they were not happy with teledermatology, and most of them declared that they were not at all happy,” according to Mariano Suppa, MD, PhD, of the department of dermatology and venereology, Free University of Brussels.

“It was very interesting: it was not just about the lack of a good quality of consultation, but was also related to some extent to a lack of respect from some patients, and also a lack of empathy. The majority of survey respondents felt [attacked] by their own patients because they were proposing teledermatology. So, yes, we were forced to go to teledermatology, and I think we will be again to some extent, but clearly we’re not happy about it,” he elaborated in response to a question from session chair Brigitte Dreno, MD, professor of dermatology and vice dean of the faculty of medicine at the University of Nantes (France).

The survey, conducted by the EADV communication committee, assessed the pandemic’s impact on European dermatologists’ professional practices and personal lives through 30 brief questions, with space at the end for additional open-ended comments. In the comments section, many dermatologists vented about their income loss, the disorganized response to round one of the pandemic, and most of all about teledermatology. Common complaints were that teledermatology required a huge consumption of energy and constituted a major intrusion upon the physicians’ personal lives. And then there was the common theme of unkind treatment by some patients.

The survey was sent twice in June 2020 to more than 4,800 EADV members. It was completed by 490 dermatologists from 39 countries. Dr. Suppa attributed the low response rate to physician weariness of the topic due to saturation news media coverage of the pandemic.

Sixty-nine percent of responding dermatologists were women. Fifty-two percent of participants were over age 50, 81% lived in a city, and 53% worked in a university or public hospital or clinic. Twelve percent lived alone.

Impact on professional practice

Many European dermatologists were on the front lines in dealing with the first wave of COVID-19. Twenty-eight percent worked in a COVID-19 unit. Forty-eight percent of dermatologists performed COVID-19 tests, and those who didn’t either had no patient contact or couldn’t get test kits. Thirty-five percent of dermatologists saw patients who presented with skin signs of COVID-19. Four percent of survey respondents became infected.

Seventy percent rescheduled or canceled all or most patient appointments. Clinical care was prioritized: during the peak of the pandemic, 76% of dermatologists saw only urgent cases – mostly potentially serious rashes – and dermato-oncology patients. Seventy-six percent of dermatologists performed teledermatology, although by June 60% of respondents reported seeing at least three-quarters of their patients face-to-face.

Twenty-three percent of dermatologists reported having lost most or all of their income during March through June, and another 26% lost about half.
 

Impact on dermatologists’ personal lives

About half of survey respondents reported feeling stressed, and a similar percentage checked the box marked ‘anxiety.’ Nine percent reported depressive symptoms, 15% mentioned feeling anger, 17% uselessness, and 2% admitted suicidal ideation. But 30% of dermatologists reported experiencing no negative psychological effects whatsoever stemming from the pandemic.

Sixteen percent of dermatologists reported drinking more alcohol during sequestration.

But respondents cited positive effects as well: a renewed appreciation of the importance of time, and enjoyment of the additional time spent with family and alone. Many dermatologists relished the opportunity to spend more time cooking, reading literature, doing research, listening to or playing music, and practicing yoga or meditation. And dermatologists took solace and pride in being members of the vital medical community.

Dr. Dreno asked if the survey revealed evidence of underdiagnosis and undertreatment of dermatologic diseases during the pandemic. Dr. Suppa replied that the survey didn’t address that issue, but it’s his personal opinion that this was no doubt the case. Roughly one-quarter of dermatologists canceled all appointments, and when dermatology clinics became filled beginning in June, he and his colleagues saw a number of cases of delayed-diagnosis advanced skin cancer.

“I think that the diseases that were really penalized were the chronic inflammatory diseases, such as psoriasis, hidradenitis suppurativa, and also atopic dermatitis. We were doing a lot of telephone consultations for those patients at that time, and we saw in June that for those particular patients there was an unmet need in the pandemic because some of them really needed to have been seen. I think this is a lesson we should learn for the second wave that we’re unfortunately facing right now: We need to adopt restrictive measures to avoid spreading the pandemic, yes, for sure, but we need to keep in mind that there is not just COVID-19, but also other important diseases,” Dr. Suppa said.

A second EADV survey will be performed during the fall/winter wave of the pandemic.

Dr. Suppa reported having no financial conflicts regarding the EADV-funded survey.
 

[email protected]

SOURCE: Suppa M. EADV 2020. Presentation D3T03.4D

European dermatologists shifted en masse to teledermatology during the first wave of the COVID-19 pandemic, and most of them disliked the videoconferencing experience intensely, according to the findings of a survey presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“The results of our survey clearly show 7 out of 10 participating dermatologists declared that they were not happy with teledermatology, and most of them declared that they were not at all happy,” according to Mariano Suppa, MD, PhD, of the department of dermatology and venereology, Free University of Brussels.

“It was very interesting: it was not just about the lack of a good quality of consultation, but was also related to some extent to a lack of respect from some patients, and also a lack of empathy. The majority of survey respondents felt [attacked] by their own patients because they were proposing teledermatology. So, yes, we were forced to go to teledermatology, and I think we will be again to some extent, but clearly we’re not happy about it,” he elaborated in response to a question from session chair Brigitte Dreno, MD, professor of dermatology and vice dean of the faculty of medicine at the University of Nantes (France).

The survey, conducted by the EADV communication committee, assessed the pandemic’s impact on European dermatologists’ professional practices and personal lives through 30 brief questions, with space at the end for additional open-ended comments. In the comments section, many dermatologists vented about their income loss, the disorganized response to round one of the pandemic, and most of all about teledermatology. Common complaints were that teledermatology required a huge consumption of energy and constituted a major intrusion upon the physicians’ personal lives. And then there was the common theme of unkind treatment by some patients.

The survey was sent twice in June 2020 to more than 4,800 EADV members. It was completed by 490 dermatologists from 39 countries. Dr. Suppa attributed the low response rate to physician weariness of the topic due to saturation news media coverage of the pandemic.

Sixty-nine percent of responding dermatologists were women. Fifty-two percent of participants were over age 50, 81% lived in a city, and 53% worked in a university or public hospital or clinic. Twelve percent lived alone.

Impact on professional practice

Many European dermatologists were on the front lines in dealing with the first wave of COVID-19. Twenty-eight percent worked in a COVID-19 unit. Forty-eight percent of dermatologists performed COVID-19 tests, and those who didn’t either had no patient contact or couldn’t get test kits. Thirty-five percent of dermatologists saw patients who presented with skin signs of COVID-19. Four percent of survey respondents became infected.

Seventy percent rescheduled or canceled all or most patient appointments. Clinical care was prioritized: during the peak of the pandemic, 76% of dermatologists saw only urgent cases – mostly potentially serious rashes – and dermato-oncology patients. Seventy-six percent of dermatologists performed teledermatology, although by June 60% of respondents reported seeing at least three-quarters of their patients face-to-face.

Twenty-three percent of dermatologists reported having lost most or all of their income during March through June, and another 26% lost about half.
 

Impact on dermatologists’ personal lives

About half of survey respondents reported feeling stressed, and a similar percentage checked the box marked ‘anxiety.’ Nine percent reported depressive symptoms, 15% mentioned feeling anger, 17% uselessness, and 2% admitted suicidal ideation. But 30% of dermatologists reported experiencing no negative psychological effects whatsoever stemming from the pandemic.

Sixteen percent of dermatologists reported drinking more alcohol during sequestration.

But respondents cited positive effects as well: a renewed appreciation of the importance of time, and enjoyment of the additional time spent with family and alone. Many dermatologists relished the opportunity to spend more time cooking, reading literature, doing research, listening to or playing music, and practicing yoga or meditation. And dermatologists took solace and pride in being members of the vital medical community.

Dr. Dreno asked if the survey revealed evidence of underdiagnosis and undertreatment of dermatologic diseases during the pandemic. Dr. Suppa replied that the survey didn’t address that issue, but it’s his personal opinion that this was no doubt the case. Roughly one-quarter of dermatologists canceled all appointments, and when dermatology clinics became filled beginning in June, he and his colleagues saw a number of cases of delayed-diagnosis advanced skin cancer.

“I think that the diseases that were really penalized were the chronic inflammatory diseases, such as psoriasis, hidradenitis suppurativa, and also atopic dermatitis. We were doing a lot of telephone consultations for those patients at that time, and we saw in June that for those particular patients there was an unmet need in the pandemic because some of them really needed to have been seen. I think this is a lesson we should learn for the second wave that we’re unfortunately facing right now: We need to adopt restrictive measures to avoid spreading the pandemic, yes, for sure, but we need to keep in mind that there is not just COVID-19, but also other important diseases,” Dr. Suppa said.

A second EADV survey will be performed during the fall/winter wave of the pandemic.

Dr. Suppa reported having no financial conflicts regarding the EADV-funded survey.
 

[email protected]

SOURCE: Suppa M. EADV 2020. Presentation D3T03.4D

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

[email protected]

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

[email protected]

Biologic therapy for psoriasis may protect against severe COVID-19, according to two large observational studies from Italy and France presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

“Biologics seem to be very protective against severe, poor-prognosis COVID-19, but they do not prevent infection with the virus,” reported Giovanni Damiani, MD, a dermatologist at the University of Milan.

This apparent protective effect of biologic agents against severe and even fatal COVID-19 is all the more impressive because the psoriasis patients included in the Italian study – as is true of those elsewhere throughout the world – had relatively high rates of obesity, smoking, and chronic obstructive pulmonary disease, known risk factors for severe COVID-19, he added.

He presented a case-control study including 1,193 adult psoriasis patients on biologics or apremilast (Otezla) at Milan’s San Donato Hospital during the period from Feb. 21 to April 9, 2020. The control group comprised more than 10 million individuals, the entire adult population of the Lombardy region, of which Milan is the capital. This was the hardest-hit area in all of Italy during the first wave of COVID-19.

Twenty-two of the 1,193 psoriasis patients experienced confirmed COVID-19 during the study period. Seventeen were quarantined at home because their disease was mild. Five were hospitalized. But no psoriasis patients were placed in intensive care, and none died.

Psoriasis patients on biologics were significantly more likely than the general Lombardian population to test positive for COVID-19, with an unadjusted odds ratio of 3.43. They were at 9.05-fold increased risk of home quarantine for mild disease, and at 3.59-fold greater risk than controls for hospitalization for COVID-19. However, they were not at significantly increased risk of ICU admission. And while they actually had a 59% relative risk reduction for death, this didn’t achieve statistical significance.

Forty-five percent of the psoriasis patients were on an interleukin-17 (IL-17) inhibitor, 22% were on a tumor necrosis factor–alpha inhibitor, and 20% were taking an IL-12/23 inhibitor. Of note, none of 77 patients on apremilast developed COVID-19, even though it is widely considered a less potent psoriasis therapy than the injectable monoclonal antibody biologics.

The French experience

Anne-Claire Fougerousse, MD, and her French coinvestigators conducted a study designed to address a different question: Is it safe to start psoriasis patients on biologics or older conventional systemic agents such as methotrexate during the pandemic?

She presented a French national cross-sectional study of 1,418 adult psoriasis patients on a biologic or standard systemic therapy during a snapshot in time near the peak of the first wave of the pandemic in France: the period from April 27 to May 7, 2020. The group included 1,188 psoriasis patients on maintenance therapy and 230 who had initiated systemic treatment within the past 4 months. More than one-third of the patients had at least one risk factor for severe COVID-19.

Although testing wasn’t available to confirm all cases, 54 patients developed probable COVID-19 during the study period. Only five required hospitalization. None died. The two hospitalized psoriasis patients admitted to an ICU had obesity as a risk factor for severe COVID-19, as did another of the five hospitalized patients, reported Dr. Fougerousse, a dermatologist at the Bégin Military Teaching Hospital in Saint-Mandé, France. Hospitalization for COVID-19 was required in 0.43% of the French treatment initiators, not significantly different from the 0.34% rate in patients on maintenance systemic therapy. A study limitation was the lack of a control group.

Nonetheless, the data did answer the investigators’ main question: “This is the first data showing no increased incidence of severe COVID-19 in psoriasis patients receiving systemic therapy in the treatment initiation period compared to those on maintenance therapy. This may now allow physicians to initiate conventional systemic or biologic therapy in patients with severe psoriasis on a case-by-case basis in the context of the persistent COVID-19 pandemic,” Dr. Fougerousse concluded.


 

Proposed mechanism of benefit

The Italian study findings that biologics boost the risk of infection with the SARS-CoV-2 virus in psoriasis patients while potentially protecting them against ICU admission and death are backed by a biologically plausible albeit as yet unproven mechanism of action, Dr. Damiani asserted.

He elaborated: A vast body of high-quality clinical trials data demonstrates that these targeted immunosuppressive agents are associated with modestly increased risk of viral infections, including both skin and respiratory tract infections. So there is no reason to suppose these agents would offer protection against the first phase of COVID-19, involving SARS-CoV-2 infection, nor protect against the second (pulmonary phase), whose hallmarks are dyspnea with or without hypoxia. But progression to the third phase, involving hyperinflammation and hypercoagulation – dubbed the cytokine storm – could be a different matter.

“Of particular interest was that our patients on IL-17 inhibitors displayed a really great outcome. Interleukin-17 has procoagulant and prothrombotic effects, organizes bronchoalveolar remodeling, has a profibrotic effect, induces mitochondrial dysfunction, and encourages dendritic cell migration in peribronchial lymph nodes. Therefore, by antagonizing this interleukin, we may have a better prognosis, although further studies are needed to be certain,” Dr. Damiani commented.
 

Publication of his preliminary findings drew the attention of a group of highly respected thought leaders in psoriasis, including James G. Krueger, MD, head of the laboratory for investigative dermatology and codirector of the center for clinical and investigative science at Rockefeller University, New York.

The Italian report prompted them to analyze data from the phase 4, double-blind, randomized ObePso-S study investigating the effects of the IL-17 inhibitor secukinumab (Cosentyx) on systemic inflammatory markers and gene expression in psoriasis patients. The investigators demonstrated that IL-17–mediated inflammation in psoriasis patients was associated with increased expression of the angiotensin-converting enzyme 2 (ACE2) receptor in lesional skin, and that treatment with secukinumab dropped ACE2 expression to levels seen in nonlesional skin. Given that ACE2 is the chief portal of entry for SARS-CoV-2 and that IL-17 exerts systemic proinflammatory effects, it’s plausible that inhibition of IL-17–mediated inflammation via dampening of ACE2 expression in noncutaneous epithelia “could prove to be advantageous in patients with psoriasis who are at risk for SARS-CoV-2 infection,” according to Dr. Krueger and his coinvestigators in the Journal of Allergy and Clinical Immunology.

Dr. Damiani and Dr. Fougerousse reported having no financial conflicts regarding their studies. The secukinumab/ACE2 receptor study was funded by Novartis.
 

[email protected]

No clinically meaningful changes in laboratory values occurred in adolescents during 52 weeks on dupilumab for atopic dermatitis in a large, open-label safety study, Michael J. Cork, MBBS, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

These reassuring results from the ongoing LIBERTY AD PED-OLE study confirm that, as previously established in adults, no blood monitoring is required in adolescents on the monoclonal antibody, which inhibits signaling of interleukins-4 and -13, said Dr. Cork, professor of dermatology and head of Sheffield Dermatology Research at the University of Sheffield (England).

“The practical importance of this finding is that there are no other systemic drugs available that don’t require blood samples. Cyclosporine, methotrexate, and the others used for atopic dermatitis require a lot of blood monitoring, and they’re off-license anyway for use in children and adolescents,” he said in an interview.

Many pediatric patients are afraid of needles and have an intense dislike of blood draws. And in a pandemic, no one wants to come into the office for blood draws if they don’t need to.

“Blood draws are very different from the injection for dupilumab. Taking a blood sample is much more painful for children. The needle in the autoinjector is really, really tiny; you can hardly feel it, and with the autoinjector you can’t even see it,” noted Dr. Cork, who is both a pediatric and adult dermatologist.

This report from the ongoing LIBERTY AD PED-OLE study included 105 patients aged 12-17 years who completed 52 weeks on dupilumab (Dupixent) with assessments of hematologic and serum chemistry parameters at baseline and weeks 16 and 52.

“The results were anticipated, but we want to know the drug is safe in every age group. The immune system is different in different age groups, so we have to be really careful,” Dr. Cork said.

The clinical side-effect profile was the same as in adults, consisting mainly of mild conjunctivitis and injection-site reactions. It’s a much less problematic side effect picture than with the older drugs.

“We’re finding the conjunctivitis to be slightly less severe than in adults, maybe because we’ve learned from the first trials in adults and from clinical experience to use prophylactic therapy. There would be no child going on dupilumab now – and no adult – that I wouldn’t put on prophylactic eye drops with replacement tears. I start them 2 weeks before I start dupilumab,” the dermatologist explained.

He and others with extensive experience using the biologic agent also work closely with an ophthalmologist.

“If we see an eye problem before going on dupilumab we get an assessment and then ophthalmologic monitoring during treatment,” Dr. Cork said.

As a dermatologist specializing in atopic dermatitis, he confessed to feeling deprived over the years as he watched the multitude of targeted biologic agents being developed for psoriasis. When he became involved in the first pediatric clinical trials of dupilumab, he had a realization: “It’s a miraculous treatment.”

“The first child I put on dupilumab spent 70 days in the hospital for IV antibiotics in the prior year. Seventy days! He almost died from MRSA septicemia. His serum IgE was 155,000 kU/L. And his IgE just went down and down and down as the dupilumab took effect. It was just incredible,” he recalled.

Dr. Cork reported receiving research funding from and serving as a consultant to Sanofi and Regeneron, which fund the LIBERTY AD PED-OLE study, as well as numerous other pharmaceutical companies.

[email protected]

SOURCE: Cork MJ. EADV 2020, Abstract 1772.

No clinically meaningful changes in laboratory values occurred in adolescents during 52 weeks on dupilumab for atopic dermatitis in a large, open-label safety study, Michael J. Cork, MBBS, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

These reassuring results from the ongoing LIBERTY AD PED-OLE study confirm that, as previously established in adults, no blood monitoring is required in adolescents on the monoclonal antibody, which inhibits signaling of interleukins-4 and -13, said Dr. Cork, professor of dermatology and head of Sheffield Dermatology Research at the University of Sheffield (England).

“The practical importance of this finding is that there are no other systemic drugs available that don’t require blood samples. Cyclosporine, methotrexate, and the others used for atopic dermatitis require a lot of blood monitoring, and they’re off-license anyway for use in children and adolescents,” he said in an interview.

Many pediatric patients are afraid of needles and have an intense dislike of blood draws. And in a pandemic, no one wants to come into the office for blood draws if they don’t need to.

“Blood draws are very different from the injection for dupilumab. Taking a blood sample is much more painful for children. The needle in the autoinjector is really, really tiny; you can hardly feel it, and with the autoinjector you can’t even see it,” noted Dr. Cork, who is both a pediatric and adult dermatologist.

This report from the ongoing LIBERTY AD PED-OLE study included 105 patients aged 12-17 years who completed 52 weeks on dupilumab (Dupixent) with assessments of hematologic and serum chemistry parameters at baseline and weeks 16 and 52.

“The results were anticipated, but we want to know the drug is safe in every age group. The immune system is different in different age groups, so we have to be really careful,” Dr. Cork said.

The clinical side-effect profile was the same as in adults, consisting mainly of mild conjunctivitis and injection-site reactions. It’s a much less problematic side effect picture than with the older drugs.

“We’re finding the conjunctivitis to be slightly less severe than in adults, maybe because we’ve learned from the first trials in adults and from clinical experience to use prophylactic therapy. There would be no child going on dupilumab now – and no adult – that I wouldn’t put on prophylactic eye drops with replacement tears. I start them 2 weeks before I start dupilumab,” the dermatologist explained.

He and others with extensive experience using the biologic agent also work closely with an ophthalmologist.

“If we see an eye problem before going on dupilumab we get an assessment and then ophthalmologic monitoring during treatment,” Dr. Cork said.

As a dermatologist specializing in atopic dermatitis, he confessed to feeling deprived over the years as he watched the multitude of targeted biologic agents being developed for psoriasis. When he became involved in the first pediatric clinical trials of dupilumab, he had a realization: “It’s a miraculous treatment.”

“The first child I put on dupilumab spent 70 days in the hospital for IV antibiotics in the prior year. Seventy days! He almost died from MRSA septicemia. His serum IgE was 155,000 kU/L. And his IgE just went down and down and down as the dupilumab took effect. It was just incredible,” he recalled.

Dr. Cork reported receiving research funding from and serving as a consultant to Sanofi and Regeneron, which fund the LIBERTY AD PED-OLE study, as well as numerous other pharmaceutical companies.

[email protected]

SOURCE: Cork MJ. EADV 2020, Abstract 1772.

No clinically meaningful changes in laboratory values occurred in adolescents during 52 weeks on dupilumab for atopic dermatitis in a large, open-label safety study, Michael J. Cork, MBBS, PhD, reported at the virtual annual congress of the European Academy of Dermatology and Venereology.

These reassuring results from the ongoing LIBERTY AD PED-OLE study confirm that, as previously established in adults, no blood monitoring is required in adolescents on the monoclonal antibody, which inhibits signaling of interleukins-4 and -13, said Dr. Cork, professor of dermatology and head of Sheffield Dermatology Research at the University of Sheffield (England).

“The practical importance of this finding is that there are no other systemic drugs available that don’t require blood samples. Cyclosporine, methotrexate, and the others used for atopic dermatitis require a lot of blood monitoring, and they’re off-license anyway for use in children and adolescents,” he said in an interview.

Many pediatric patients are afraid of needles and have an intense dislike of blood draws. And in a pandemic, no one wants to come into the office for blood draws if they don’t need to.

“Blood draws are very different from the injection for dupilumab. Taking a blood sample is much more painful for children. The needle in the autoinjector is really, really tiny; you can hardly feel it, and with the autoinjector you can’t even see it,” noted Dr. Cork, who is both a pediatric and adult dermatologist.

This report from the ongoing LIBERTY AD PED-OLE study included 105 patients aged 12-17 years who completed 52 weeks on dupilumab (Dupixent) with assessments of hematologic and serum chemistry parameters at baseline and weeks 16 and 52.

“The results were anticipated, but we want to know the drug is safe in every age group. The immune system is different in different age groups, so we have to be really careful,” Dr. Cork said.

The clinical side-effect profile was the same as in adults, consisting mainly of mild conjunctivitis and injection-site reactions. It’s a much less problematic side effect picture than with the older drugs.

“We’re finding the conjunctivitis to be slightly less severe than in adults, maybe because we’ve learned from the first trials in adults and from clinical experience to use prophylactic therapy. There would be no child going on dupilumab now – and no adult – that I wouldn’t put on prophylactic eye drops with replacement tears. I start them 2 weeks before I start dupilumab,” the dermatologist explained.

He and others with extensive experience using the biologic agent also work closely with an ophthalmologist.

“If we see an eye problem before going on dupilumab we get an assessment and then ophthalmologic monitoring during treatment,” Dr. Cork said.

As a dermatologist specializing in atopic dermatitis, he confessed to feeling deprived over the years as he watched the multitude of targeted biologic agents being developed for psoriasis. When he became involved in the first pediatric clinical trials of dupilumab, he had a realization: “It’s a miraculous treatment.”

“The first child I put on dupilumab spent 70 days in the hospital for IV antibiotics in the prior year. Seventy days! He almost died from MRSA septicemia. His serum IgE was 155,000 kU/L. And his IgE just went down and down and down as the dupilumab took effect. It was just incredible,” he recalled.

Dr. Cork reported receiving research funding from and serving as a consultant to Sanofi and Regeneron, which fund the LIBERTY AD PED-OLE study, as well as numerous other pharmaceutical companies.

[email protected]

SOURCE: Cork MJ. EADV 2020, Abstract 1772.

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

COVID-19–positive patients undergoing an invasive strategy for acute coronary syndrome presented hours later than uninfected historical controls, had a far higher incidence of cardiogenic shock, and their in-hospital mortality rate was four- to fivefold greater, according to data from the Global Multicenter Prospective COVID–ACS Registry. These phenomena are probably interrelated, according to Anthony Gershlick, MBBS, who presented the registry results at the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

“We know that increasing ischemic time leads to bigger infarcts. And we know that bigger infarcts lead to cardiogenic shock, with its known higher mortality,” said Dr. Gershlick, professor of interventional cardiology at the University of Leicester (England).

“These data suggest that patients may have presented late, likely due to COVID concerns, and they had worse outcomes. If these data are borne out, future public information strategies need to be reassuring, proactive, simple, and more effective because we think patients stayed away,” the cardiologist added. “There are important public information messages to be taken from these data about getting patients to come to hospital during such pandemics.”

He presented prospectively collected registry data on 144 patients with confirmed ST-elevation MI (STEMI) and 122 with non-ST–elevation MI (NSTEMI), all COVID-19 positive on presentation at 85 hospitals in the United Kingdom, Europe, and North America during March through August of 2020. Since the initial message to the public early in the pandemic in many places was to try to avoid the hospital, the investigators selected for their no-COVID comparison group the data on more than 22,000 STEMI and NSTEMI patients included in two British national databases covering 2018-2019.

The COVID-positive STEMI patients were significantly younger, had more comorbidities, and had a higher mean heart rate and lower systolic blood pressure at admission than the non-COVID STEMI control group. Their median time from symptom onset to admission was 339 minutes, compared with 178 minutes in controls. Their door-to-balloon time averaged 83 minutes, versus 37 minutes in the era before the pandemic.

“I suspect that’s got something to do with the donning and doffing of personal protective equipment,” he said at the meeting sponsored by the Cardiovascular Research Foundation.

The in-hospital mortality rates were strikingly different: 27.1% in COVID-positive STEMI patients versus 5.7% in controls. Bleeding Academic Research Consortium type 3-5 bleeding was increased as well, by a margin of 2.8% to 0.3%. So was stroke, with a 2.1% in-hospital incidence in COVID-positive STEMI patients and a 0.1% rate in the comparator arm.

“But the biggest headline here for me was that the cardiogenic shock rate was 20.1% in the COVID-positive patients versus 8.7% in the non-COVID STEMI patients,” the cardiologist continued.

The same pattern held true among the COVID-positive NSTEMI patients: They were younger, sicker, and slower to present to the hospital than the non-COVID group. The in-hospital mortality rate was 6.6% in the COVID-positive NSTEMI patients, compared with 1.2% in the reference group. The COVID-positive patients had a 2.5% bleeding rate versus 0.1% in the controls. And the incidence of cardiogenic shock was 5%, compared with 1.4% in the controls from before the pandemic.

“Even though NSTEMI is traditionally regarded as lower risk, this is really quite dramatic. These are sick patients,” Dr. Gershlick observed.

Nearly two-thirds of in-hospital deaths in COVID-positive ACS patients were cardiovascular, and three-quarters of those cardiovascular deaths occurred in patients with cardiogenic shock. Thirty-two percent of deaths in COVID-positive ACS patients were of respiratory causes, and 4.9% were neurologic.

Notably, the ischemic time of patients with cardiogenic shock who died – that is, the time from symptom onset to balloon deployment – averaged 1,271 minutes, compared with 441 minutes in those who died without being in cardiogenic shock.

Session comoderator Sahil A. Parikh, MD, director of endovascular services at Columbia University Medical Center in New York, commented, “One of the striking things that is resonating with me is the high incidence of cardiogenic shock and the mortality. It’s akin to what we’ve seen in New York.”

[email protected]

COVID-19–positive patients undergoing an invasive strategy for acute coronary syndrome presented hours later than uninfected historical controls, had a far higher incidence of cardiogenic shock, and their in-hospital mortality rate was four- to fivefold greater, according to data from the Global Multicenter Prospective COVID–ACS Registry. These phenomena are probably interrelated, according to Anthony Gershlick, MBBS, who presented the registry results at the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

“We know that increasing ischemic time leads to bigger infarcts. And we know that bigger infarcts lead to cardiogenic shock, with its known higher mortality,” said Dr. Gershlick, professor of interventional cardiology at the University of Leicester (England).

“These data suggest that patients may have presented late, likely due to COVID concerns, and they had worse outcomes. If these data are borne out, future public information strategies need to be reassuring, proactive, simple, and more effective because we think patients stayed away,” the cardiologist added. “There are important public information messages to be taken from these data about getting patients to come to hospital during such pandemics.”

He presented prospectively collected registry data on 144 patients with confirmed ST-elevation MI (STEMI) and 122 with non-ST–elevation MI (NSTEMI), all COVID-19 positive on presentation at 85 hospitals in the United Kingdom, Europe, and North America during March through August of 2020. Since the initial message to the public early in the pandemic in many places was to try to avoid the hospital, the investigators selected for their no-COVID comparison group the data on more than 22,000 STEMI and NSTEMI patients included in two British national databases covering 2018-2019.

The COVID-positive STEMI patients were significantly younger, had more comorbidities, and had a higher mean heart rate and lower systolic blood pressure at admission than the non-COVID STEMI control group. Their median time from symptom onset to admission was 339 minutes, compared with 178 minutes in controls. Their door-to-balloon time averaged 83 minutes, versus 37 minutes in the era before the pandemic.

“I suspect that’s got something to do with the donning and doffing of personal protective equipment,” he said at the meeting sponsored by the Cardiovascular Research Foundation.

The in-hospital mortality rates were strikingly different: 27.1% in COVID-positive STEMI patients versus 5.7% in controls. Bleeding Academic Research Consortium type 3-5 bleeding was increased as well, by a margin of 2.8% to 0.3%. So was stroke, with a 2.1% in-hospital incidence in COVID-positive STEMI patients and a 0.1% rate in the comparator arm.

“But the biggest headline here for me was that the cardiogenic shock rate was 20.1% in the COVID-positive patients versus 8.7% in the non-COVID STEMI patients,” the cardiologist continued.

The same pattern held true among the COVID-positive NSTEMI patients: They were younger, sicker, and slower to present to the hospital than the non-COVID group. The in-hospital mortality rate was 6.6% in the COVID-positive NSTEMI patients, compared with 1.2% in the reference group. The COVID-positive patients had a 2.5% bleeding rate versus 0.1% in the controls. And the incidence of cardiogenic shock was 5%, compared with 1.4% in the controls from before the pandemic.

“Even though NSTEMI is traditionally regarded as lower risk, this is really quite dramatic. These are sick patients,” Dr. Gershlick observed.

Nearly two-thirds of in-hospital deaths in COVID-positive ACS patients were cardiovascular, and three-quarters of those cardiovascular deaths occurred in patients with cardiogenic shock. Thirty-two percent of deaths in COVID-positive ACS patients were of respiratory causes, and 4.9% were neurologic.

Notably, the ischemic time of patients with cardiogenic shock who died – that is, the time from symptom onset to balloon deployment – averaged 1,271 minutes, compared with 441 minutes in those who died without being in cardiogenic shock.

Session comoderator Sahil A. Parikh, MD, director of endovascular services at Columbia University Medical Center in New York, commented, “One of the striking things that is resonating with me is the high incidence of cardiogenic shock and the mortality. It’s akin to what we’ve seen in New York.”

[email protected]

COVID-19–positive patients undergoing an invasive strategy for acute coronary syndrome presented hours later than uninfected historical controls, had a far higher incidence of cardiogenic shock, and their in-hospital mortality rate was four- to fivefold greater, according to data from the Global Multicenter Prospective COVID–ACS Registry. These phenomena are probably interrelated, according to Anthony Gershlick, MBBS, who presented the registry results at the Transcatheter Cardiovascular Therapeutics virtual annual meeting.

“We know that increasing ischemic time leads to bigger infarcts. And we know that bigger infarcts lead to cardiogenic shock, with its known higher mortality,” said Dr. Gershlick, professor of interventional cardiology at the University of Leicester (England).

“These data suggest that patients may have presented late, likely due to COVID concerns, and they had worse outcomes. If these data are borne out, future public information strategies need to be reassuring, proactive, simple, and more effective because we think patients stayed away,” the cardiologist added. “There are important public information messages to be taken from these data about getting patients to come to hospital during such pandemics.”

He presented prospectively collected registry data on 144 patients with confirmed ST-elevation MI (STEMI) and 122 with non-ST–elevation MI (NSTEMI), all COVID-19 positive on presentation at 85 hospitals in the United Kingdom, Europe, and North America during March through August of 2020. Since the initial message to the public early in the pandemic in many places was to try to avoid the hospital, the investigators selected for their no-COVID comparison group the data on more than 22,000 STEMI and NSTEMI patients included in two British national databases covering 2018-2019.

The COVID-positive STEMI patients were significantly younger, had more comorbidities, and had a higher mean heart rate and lower systolic blood pressure at admission than the non-COVID STEMI control group. Their median time from symptom onset to admission was 339 minutes, compared with 178 minutes in controls. Their door-to-balloon time averaged 83 minutes, versus 37 minutes in the era before the pandemic.

“I suspect that’s got something to do with the donning and doffing of personal protective equipment,” he said at the meeting sponsored by the Cardiovascular Research Foundation.

The in-hospital mortality rates were strikingly different: 27.1% in COVID-positive STEMI patients versus 5.7% in controls. Bleeding Academic Research Consortium type 3-5 bleeding was increased as well, by a margin of 2.8% to 0.3%. So was stroke, with a 2.1% in-hospital incidence in COVID-positive STEMI patients and a 0.1% rate in the comparator arm.

“But the biggest headline here for me was that the cardiogenic shock rate was 20.1% in the COVID-positive patients versus 8.7% in the non-COVID STEMI patients,” the cardiologist continued.

The same pattern held true among the COVID-positive NSTEMI patients: They were younger, sicker, and slower to present to the hospital than the non-COVID group. The in-hospital mortality rate was 6.6% in the COVID-positive NSTEMI patients, compared with 1.2% in the reference group. The COVID-positive patients had a 2.5% bleeding rate versus 0.1% in the controls. And the incidence of cardiogenic shock was 5%, compared with 1.4% in the controls from before the pandemic.

“Even though NSTEMI is traditionally regarded as lower risk, this is really quite dramatic. These are sick patients,” Dr. Gershlick observed.

Nearly two-thirds of in-hospital deaths in COVID-positive ACS patients were cardiovascular, and three-quarters of those cardiovascular deaths occurred in patients with cardiogenic shock. Thirty-two percent of deaths in COVID-positive ACS patients were of respiratory causes, and 4.9% were neurologic.

Notably, the ischemic time of patients with cardiogenic shock who died – that is, the time from symptom onset to balloon deployment – averaged 1,271 minutes, compared with 441 minutes in those who died without being in cardiogenic shock.

Session comoderator Sahil A. Parikh, MD, director of endovascular services at Columbia University Medical Center in New York, commented, “One of the striking things that is resonating with me is the high incidence of cardiogenic shock and the mortality. It’s akin to what we’ve seen in New York.”

[email protected]

No hint of increased mortality risk in association with the use of paclitaxel-coated devices for treatment of peripheral artery disease was detected in VOYAGER PAD, a multithousand-patient randomized trial with long-term follow-up and ascertainment of vital status in 99.6% of participants.

Observers opined that the VOYAGER PAD findings effectively put to rest a nearly 2-year-old controversy over whether paclitaxel-coated devices for treatment of peripheral artery disease (PAD) carry an increased mortality risk. The imbroglio, which was ignited by a meta-analysis of clinical trials with substantial amounts of missing follow-up data, triggered an Food and Drug Administration warning letter to health care providers which threw the field of vascular medicine into disarray.

“Although as a community we’ve continued to struggle with this issue of paclitaxel and mortality, VOYAGER PAD does fill many of the gaps and addresses many of the limitations of currently available data,” Connie N. Hess, MD, said in reporting results of a prespecified analysis of the trial at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting. “I think these are the most definitive data to date supporting the safety of drug-coated device use.”

VOYAGER PAD was a double-blind, placebo-controlled clinical trial in which 6,564 patients undergoing lower-extremity revascularization for symptomatic PAD were randomized to rivaroxaban at 2.5 mg twice daily or placebo on top of background low-dose aspirin. In the previously reported primary outcome, the group on rivaroxaban plus aspirin had a significant 15% reduction in the risk of the composite endpoint of cardiovascular death, acute limb ischemia, MI, ischemic stroke, or major amputation for vascular causes.

Of the 4,316 patients included in the prespecified analysis by Dr. Hess, a cardiologist at the University of Colorado at Denver, Aurora, 31% received a paclitaxel-coated device. At 3.5 years of follow-up, they had a 10.2% all-cause mortality rate, significantly less than the 13.5% rate in patients who didn’t get a drug-coated device. But since study participants weren’t randomized for drug-coated device use, the investigators utilized a rigorous form of propensity adjustment called inverse probability treatment weighting to neutralize all between-group differences in potentially confounding baseline characteristics, including statin use, prevalence of claudication, and target lesion length.

In the weighted analysis, the all-cause mortality rate at 3.5 years was 12.1% in paclitaxel-coated device recipients and 12.6% in those who didn’t get such devices. The difference was not statistically significant, and the hazard ratio of 0.95 had tight confidence intervals.

“We don’t see a mortality benefit, but I think more importantly, we don’t see any risk for mortality,” the cardiologist observed at the meeting sponsored by the Cardiovascular Research Foundation.

There was no between-group difference in causes of mortality. Nor did all-cause mortality differ by device type, be it paclitaxel-coated balloon versus plain balloon angioplasty, or drug-eluting stent versus bare-metal stent.

Also, the benefit of rivaroxaban plus aspirin over aspirin alone in terms of cardiovascular and ischemic limb outcomes was consistent regardless of whether patients got a drug-coated device or not.

Discussant Robert Lookstein, MD, praised Dr. Hess for “a really enlightening presentation.”

“The entire vascular community has been waiting for a prospective, independently adjudicated trial to try to make determinations of whether we can put this issue behind us, and I think this trial is it,” said Dr. Lookstein, professor of interventional radiology and surgery at the Icahn School of Medicine at Mount Sinai, New York.

“Personally, I think this is probably the most impactful data seen regarding the paclitaxel issue in almost 2 years because it is randomized data, it’s prospectively collected data, and – most importantly from my perspective – they were able to collect vital statistics on more than 99.5% of the patients,” he added. “I think this is incredibly impactful to my practice.”

Frank Veith, MD, professor of surgery at New York University, concurred, declaring, “I think this study is a game changer. And I think the paclitaxel game is over.”

The VOYAGER PAD study was funded by institutional research grants from Bayer and Janssen.

[email protected]

No hint of increased mortality risk in association with the use of paclitaxel-coated devices for treatment of peripheral artery disease was detected in VOYAGER PAD, a multithousand-patient randomized trial with long-term follow-up and ascertainment of vital status in 99.6% of participants.

Observers opined that the VOYAGER PAD findings effectively put to rest a nearly 2-year-old controversy over whether paclitaxel-coated devices for treatment of peripheral artery disease (PAD) carry an increased mortality risk. The imbroglio, which was ignited by a meta-analysis of clinical trials with substantial amounts of missing follow-up data, triggered an Food and Drug Administration warning letter to health care providers which threw the field of vascular medicine into disarray.

“Although as a community we’ve continued to struggle with this issue of paclitaxel and mortality, VOYAGER PAD does fill many of the gaps and addresses many of the limitations of currently available data,” Connie N. Hess, MD, said in reporting results of a prespecified analysis of the trial at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting. “I think these are the most definitive data to date supporting the safety of drug-coated device use.”

VOYAGER PAD was a double-blind, placebo-controlled clinical trial in which 6,564 patients undergoing lower-extremity revascularization for symptomatic PAD were randomized to rivaroxaban at 2.5 mg twice daily or placebo on top of background low-dose aspirin. In the previously reported primary outcome, the group on rivaroxaban plus aspirin had a significant 15% reduction in the risk of the composite endpoint of cardiovascular death, acute limb ischemia, MI, ischemic stroke, or major amputation for vascular causes.

Of the 4,316 patients included in the prespecified analysis by Dr. Hess, a cardiologist at the University of Colorado at Denver, Aurora, 31% received a paclitaxel-coated device. At 3.5 years of follow-up, they had a 10.2% all-cause mortality rate, significantly less than the 13.5% rate in patients who didn’t get a drug-coated device. But since study participants weren’t randomized for drug-coated device use, the investigators utilized a rigorous form of propensity adjustment called inverse probability treatment weighting to neutralize all between-group differences in potentially confounding baseline characteristics, including statin use, prevalence of claudication, and target lesion length.

In the weighted analysis, the all-cause mortality rate at 3.5 years was 12.1% in paclitaxel-coated device recipients and 12.6% in those who didn’t get such devices. The difference was not statistically significant, and the hazard ratio of 0.95 had tight confidence intervals.

“We don’t see a mortality benefit, but I think more importantly, we don’t see any risk for mortality,” the cardiologist observed at the meeting sponsored by the Cardiovascular Research Foundation.

There was no between-group difference in causes of mortality. Nor did all-cause mortality differ by device type, be it paclitaxel-coated balloon versus plain balloon angioplasty, or drug-eluting stent versus bare-metal stent.

Also, the benefit of rivaroxaban plus aspirin over aspirin alone in terms of cardiovascular and ischemic limb outcomes was consistent regardless of whether patients got a drug-coated device or not.

Discussant Robert Lookstein, MD, praised Dr. Hess for “a really enlightening presentation.”

“The entire vascular community has been waiting for a prospective, independently adjudicated trial to try to make determinations of whether we can put this issue behind us, and I think this trial is it,” said Dr. Lookstein, professor of interventional radiology and surgery at the Icahn School of Medicine at Mount Sinai, New York.

“Personally, I think this is probably the most impactful data seen regarding the paclitaxel issue in almost 2 years because it is randomized data, it’s prospectively collected data, and – most importantly from my perspective – they were able to collect vital statistics on more than 99.5% of the patients,” he added. “I think this is incredibly impactful to my practice.”

Frank Veith, MD, professor of surgery at New York University, concurred, declaring, “I think this study is a game changer. And I think the paclitaxel game is over.”

The VOYAGER PAD study was funded by institutional research grants from Bayer and Janssen.

[email protected]

No hint of increased mortality risk in association with the use of paclitaxel-coated devices for treatment of peripheral artery disease was detected in VOYAGER PAD, a multithousand-patient randomized trial with long-term follow-up and ascertainment of vital status in 99.6% of participants.

Observers opined that the VOYAGER PAD findings effectively put to rest a nearly 2-year-old controversy over whether paclitaxel-coated devices for treatment of peripheral artery disease (PAD) carry an increased mortality risk. The imbroglio, which was ignited by a meta-analysis of clinical trials with substantial amounts of missing follow-up data, triggered an Food and Drug Administration warning letter to health care providers which threw the field of vascular medicine into disarray.

“Although as a community we’ve continued to struggle with this issue of paclitaxel and mortality, VOYAGER PAD does fill many of the gaps and addresses many of the limitations of currently available data,” Connie N. Hess, MD, said in reporting results of a prespecified analysis of the trial at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting. “I think these are the most definitive data to date supporting the safety of drug-coated device use.”

VOYAGER PAD was a double-blind, placebo-controlled clinical trial in which 6,564 patients undergoing lower-extremity revascularization for symptomatic PAD were randomized to rivaroxaban at 2.5 mg twice daily or placebo on top of background low-dose aspirin. In the previously reported primary outcome, the group on rivaroxaban plus aspirin had a significant 15% reduction in the risk of the composite endpoint of cardiovascular death, acute limb ischemia, MI, ischemic stroke, or major amputation for vascular causes.

Of the 4,316 patients included in the prespecified analysis by Dr. Hess, a cardiologist at the University of Colorado at Denver, Aurora, 31% received a paclitaxel-coated device. At 3.5 years of follow-up, they had a 10.2% all-cause mortality rate, significantly less than the 13.5% rate in patients who didn’t get a drug-coated device. But since study participants weren’t randomized for drug-coated device use, the investigators utilized a rigorous form of propensity adjustment called inverse probability treatment weighting to neutralize all between-group differences in potentially confounding baseline characteristics, including statin use, prevalence of claudication, and target lesion length.

In the weighted analysis, the all-cause mortality rate at 3.5 years was 12.1% in paclitaxel-coated device recipients and 12.6% in those who didn’t get such devices. The difference was not statistically significant, and the hazard ratio of 0.95 had tight confidence intervals.

“We don’t see a mortality benefit, but I think more importantly, we don’t see any risk for mortality,” the cardiologist observed at the meeting sponsored by the Cardiovascular Research Foundation.

There was no between-group difference in causes of mortality. Nor did all-cause mortality differ by device type, be it paclitaxel-coated balloon versus plain balloon angioplasty, or drug-eluting stent versus bare-metal stent.

Also, the benefit of rivaroxaban plus aspirin over aspirin alone in terms of cardiovascular and ischemic limb outcomes was consistent regardless of whether patients got a drug-coated device or not.

Discussant Robert Lookstein, MD, praised Dr. Hess for “a really enlightening presentation.”

“The entire vascular community has been waiting for a prospective, independently adjudicated trial to try to make determinations of whether we can put this issue behind us, and I think this trial is it,” said Dr. Lookstein, professor of interventional radiology and surgery at the Icahn School of Medicine at Mount Sinai, New York.

“Personally, I think this is probably the most impactful data seen regarding the paclitaxel issue in almost 2 years because it is randomized data, it’s prospectively collected data, and – most importantly from my perspective – they were able to collect vital statistics on more than 99.5% of the patients,” he added. “I think this is incredibly impactful to my practice.”

Frank Veith, MD, professor of surgery at New York University, concurred, declaring, “I think this study is a game changer. And I think the paclitaxel game is over.”

The VOYAGER PAD study was funded by institutional research grants from Bayer and Janssen.

[email protected]

Patients with severe melancholic or psychotic depression are more likely to respond to ECT, and preliminary evidence indicates they’re also protected against ECT-induced cognitive impairment, Linda van Diermen, MD, PhD, reported at the virtual congress of the European College of Neuropsychopharmacology.

Over the decades many small, underpowered studies have looked at possible predictors of ECT response and remission, with no consensus being reached. In an effort to bring a measure of clarity, Dr. van Diermen and her coinvestigators performed a meta-analysis of 34 published studies in accord with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-analysis Protocols) guidelines and published their findings in the British Journal of Psychiatry. They scrutinized three potential predictors of response: the presence of psychotic features, melancholic depression with psychomotor symptoms, and older age.

Psychotic depression was associated with a 1.7-fold increased likelihood of response to ECT and a 1.5-fold increased odds of remission, compared with that of ECT-treated patients without psychotic depression. Older age was also a statistically significant predictor of response. However, the findings on melancholic depression were inconclusive, with only five studies with inconsistent results being available, said Dr. van Diermen, a psychiatrist at the University of Antwerp (Belgium).

She was quick to point out that, although psychotic depression and older age were statistically significant predictors of heightened likelihood of ECT response, they are of only limited clinical significance in treatment decision-making. The ECT response rate was 79% in patients with psychotic depression but still quite good at 71% in those without psychotic depression. Moreover, the average age of remitters was 59.7 years, compared with 55.4 years in nonresponders, a difference too small to be useful in guiding clinical treatment decisions.

“Age is not a valuable ECT predictor,” she said. “Although we did a meta-analysis in more than 3,200 patients that confirmed the superior effects of ECT in older patients and we recommended it at that time as one of the elements to guide decision-making when you consider ECT, our present, more detailed look at the interdependence of the predictors leads us to reconsider this statement. We now venture that age has been given too much weight in the past decades.”
 

A closer look at ECT response predictors

The studies included in the meta-analysis assessed psychotic depression and melancholic features as ECT response predictors in the typical binary way employed in clinical practice: yes/no, either present or absent. Dr. van Diermer hypothesized that a more in-depth assessment of the severity of those factors would boost their predictive power.

She found that this was indeed the case for melancholic depression as evaluated by three tools for measuring psychomotor symptoms, a core feature of this form of depression. She and her coinvestigators assessed psychomotor functioning in 65 adults with major depressive disorder before, during, and after ECT using the clinician-rated CORE scale, which measures psychomotor retardation, agitation, and noninteractiveness. In addition, the investigators had the subjects wear an accelerometer and complete a timed fine-motor drawing test.

The 41 patients with melancholic depression with psychomotor symptoms as defined by a CORE score of 8 or more were 4.9-fold more likely to reach an ECT response than were those with nonmelancholic depression. A lower baseline daytime activity level as assessed by accelerometer was also a significant predictor of increased likelihood of response, as were slower times on the drawing test.

In contrast, the investigators found that more detailed assessment of psychotic depression using the validated Psychotic Depression Assessment Scale (PDAS) was predictive of the likelihood of ECT response, but not any more so than the simple presence or absence of psychotic symptoms (J ECT. 2019 Dec;35[4]:238-44).

“In our sample, better measurement of psychotic symptoms did not improve prediction, but better measurement of psychomotor symptoms did seem to be valuable,” according to the psychiatrist.
 

Protection against ECT’s cognitive side effects?

Dr. van Diermen and colleagues assessed short- and long-term changes in global cognitive functioning in 65 consecutive patients treated with ECT for a major depressive episode by administering the Montreal Cognitive Assessment (MoCA) at baseline, before the third ECT session, and 1 week, 3 months, and 6 months after completing their treatment course.

During ECT, the investigators documented a limited decrease in cognitive functioning at the group level, which rebounded during the 6 months after ECT. But although there was no significant difference between MoCA scores at baseline and 6 months follow-up after ECT in the overall group of study participants, that doesn’t tell the full story. Six months after completing their course of ECT, 18% of patients demonstrated improved cognitive functioning, compared with baseline, but 8% had significantly worse cognitive functioning than pretreatment.

“Saying that ECT has no cognitive effects seems to be somewhat wrong to me. It has cognitive effects for certain people, and it will be interesting to know which people,” Dr. van Diermen said.

In what she termed “a very, very preliminary analysis,” she found that the patients with psychotic or melancholic depression were markedly less likely to have long-term cognitive impairment as defined by a worse MoCA score, compared with baseline, both at 6 months and one or more intermediate time points. Only 1 of 31 patients with psychotic depression fell into that poor cognitive outcome category, as did 4 patients with melancholic depression, compared with 12 patients without psychotic depression and 9 without melancholic depression. This, Dr. van Diermen believes, is the first report of an apparent protective effect of melancholic or psychotic depression against ECT-induced long-term cognitive worsening.

“Replication of our results is definitely necessary in larger patient samples,” she cautioned.

Dr. van Diermen reported having no financial conflicts regarding her presentation.

[email protected]

SOURCE: van Diermen L. ECNP 2020, Session EDU03.

Patients with severe melancholic or psychotic depression are more likely to respond to ECT, and preliminary evidence indicates they’re also protected against ECT-induced cognitive impairment, Linda van Diermen, MD, PhD, reported at the virtual congress of the European College of Neuropsychopharmacology.

Over the decades many small, underpowered studies have looked at possible predictors of ECT response and remission, with no consensus being reached. In an effort to bring a measure of clarity, Dr. van Diermen and her coinvestigators performed a meta-analysis of 34 published studies in accord with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-analysis Protocols) guidelines and published their findings in the British Journal of Psychiatry. They scrutinized three potential predictors of response: the presence of psychotic features, melancholic depression with psychomotor symptoms, and older age.

Psychotic depression was associated with a 1.7-fold increased likelihood of response to ECT and a 1.5-fold increased odds of remission, compared with that of ECT-treated patients without psychotic depression. Older age was also a statistically significant predictor of response. However, the findings on melancholic depression were inconclusive, with only five studies with inconsistent results being available, said Dr. van Diermen, a psychiatrist at the University of Antwerp (Belgium).

She was quick to point out that, although psychotic depression and older age were statistically significant predictors of heightened likelihood of ECT response, they are of only limited clinical significance in treatment decision-making. The ECT response rate was 79% in patients with psychotic depression but still quite good at 71% in those without psychotic depression. Moreover, the average age of remitters was 59.7 years, compared with 55.4 years in nonresponders, a difference too small to be useful in guiding clinical treatment decisions.

“Age is not a valuable ECT predictor,” she said. “Although we did a meta-analysis in more than 3,200 patients that confirmed the superior effects of ECT in older patients and we recommended it at that time as one of the elements to guide decision-making when you consider ECT, our present, more detailed look at the interdependence of the predictors leads us to reconsider this statement. We now venture that age has been given too much weight in the past decades.”
 

A closer look at ECT response predictors

The studies included in the meta-analysis assessed psychotic depression and melancholic features as ECT response predictors in the typical binary way employed in clinical practice: yes/no, either present or absent. Dr. van Diermer hypothesized that a more in-depth assessment of the severity of those factors would boost their predictive power.

She found that this was indeed the case for melancholic depression as evaluated by three tools for measuring psychomotor symptoms, a core feature of this form of depression. She and her coinvestigators assessed psychomotor functioning in 65 adults with major depressive disorder before, during, and after ECT using the clinician-rated CORE scale, which measures psychomotor retardation, agitation, and noninteractiveness. In addition, the investigators had the subjects wear an accelerometer and complete a timed fine-motor drawing test.

The 41 patients with melancholic depression with psychomotor symptoms as defined by a CORE score of 8 or more were 4.9-fold more likely to reach an ECT response than were those with nonmelancholic depression. A lower baseline daytime activity level as assessed by accelerometer was also a significant predictor of increased likelihood of response, as were slower times on the drawing test.

In contrast, the investigators found that more detailed assessment of psychotic depression using the validated Psychotic Depression Assessment Scale (PDAS) was predictive of the likelihood of ECT response, but not any more so than the simple presence or absence of psychotic symptoms (J ECT. 2019 Dec;35[4]:238-44).

“In our sample, better measurement of psychotic symptoms did not improve prediction, but better measurement of psychomotor symptoms did seem to be valuable,” according to the psychiatrist.
 

Protection against ECT’s cognitive side effects?

Dr. van Diermen and colleagues assessed short- and long-term changes in global cognitive functioning in 65 consecutive patients treated with ECT for a major depressive episode by administering the Montreal Cognitive Assessment (MoCA) at baseline, before the third ECT session, and 1 week, 3 months, and 6 months after completing their treatment course.

During ECT, the investigators documented a limited decrease in cognitive functioning at the group level, which rebounded during the 6 months after ECT. But although there was no significant difference between MoCA scores at baseline and 6 months follow-up after ECT in the overall group of study participants, that doesn’t tell the full story. Six months after completing their course of ECT, 18% of patients demonstrated improved cognitive functioning, compared with baseline, but 8% had significantly worse cognitive functioning than pretreatment.

“Saying that ECT has no cognitive effects seems to be somewhat wrong to me. It has cognitive effects for certain people, and it will be interesting to know which people,” Dr. van Diermen said.

In what she termed “a very, very preliminary analysis,” she found that the patients with psychotic or melancholic depression were markedly less likely to have long-term cognitive impairment as defined by a worse MoCA score, compared with baseline, both at 6 months and one or more intermediate time points. Only 1 of 31 patients with psychotic depression fell into that poor cognitive outcome category, as did 4 patients with melancholic depression, compared with 12 patients without psychotic depression and 9 without melancholic depression. This, Dr. van Diermen believes, is the first report of an apparent protective effect of melancholic or psychotic depression against ECT-induced long-term cognitive worsening.

“Replication of our results is definitely necessary in larger patient samples,” she cautioned.

Dr. van Diermen reported having no financial conflicts regarding her presentation.

[email protected]

SOURCE: van Diermen L. ECNP 2020, Session EDU03.

Patients with severe melancholic or psychotic depression are more likely to respond to ECT, and preliminary evidence indicates they’re also protected against ECT-induced cognitive impairment, Linda van Diermen, MD, PhD, reported at the virtual congress of the European College of Neuropsychopharmacology.

Over the decades many small, underpowered studies have looked at possible predictors of ECT response and remission, with no consensus being reached. In an effort to bring a measure of clarity, Dr. van Diermen and her coinvestigators performed a meta-analysis of 34 published studies in accord with the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-analysis Protocols) guidelines and published their findings in the British Journal of Psychiatry. They scrutinized three potential predictors of response: the presence of psychotic features, melancholic depression with psychomotor symptoms, and older age.

Psychotic depression was associated with a 1.7-fold increased likelihood of response to ECT and a 1.5-fold increased odds of remission, compared with that of ECT-treated patients without psychotic depression. Older age was also a statistically significant predictor of response. However, the findings on melancholic depression were inconclusive, with only five studies with inconsistent results being available, said Dr. van Diermen, a psychiatrist at the University of Antwerp (Belgium).

She was quick to point out that, although psychotic depression and older age were statistically significant predictors of heightened likelihood of ECT response, they are of only limited clinical significance in treatment decision-making. The ECT response rate was 79% in patients with psychotic depression but still quite good at 71% in those without psychotic depression. Moreover, the average age of remitters was 59.7 years, compared with 55.4 years in nonresponders, a difference too small to be useful in guiding clinical treatment decisions.

“Age is not a valuable ECT predictor,” she said. “Although we did a meta-analysis in more than 3,200 patients that confirmed the superior effects of ECT in older patients and we recommended it at that time as one of the elements to guide decision-making when you consider ECT, our present, more detailed look at the interdependence of the predictors leads us to reconsider this statement. We now venture that age has been given too much weight in the past decades.”
 

A closer look at ECT response predictors

The studies included in the meta-analysis assessed psychotic depression and melancholic features as ECT response predictors in the typical binary way employed in clinical practice: yes/no, either present or absent. Dr. van Diermer hypothesized that a more in-depth assessment of the severity of those factors would boost their predictive power.

She found that this was indeed the case for melancholic depression as evaluated by three tools for measuring psychomotor symptoms, a core feature of this form of depression. She and her coinvestigators assessed psychomotor functioning in 65 adults with major depressive disorder before, during, and after ECT using the clinician-rated CORE scale, which measures psychomotor retardation, agitation, and noninteractiveness. In addition, the investigators had the subjects wear an accelerometer and complete a timed fine-motor drawing test.

The 41 patients with melancholic depression with psychomotor symptoms as defined by a CORE score of 8 or more were 4.9-fold more likely to reach an ECT response than were those with nonmelancholic depression. A lower baseline daytime activity level as assessed by accelerometer was also a significant predictor of increased likelihood of response, as were slower times on the drawing test.

In contrast, the investigators found that more detailed assessment of psychotic depression using the validated Psychotic Depression Assessment Scale (PDAS) was predictive of the likelihood of ECT response, but not any more so than the simple presence or absence of psychotic symptoms (J ECT. 2019 Dec;35[4]:238-44).

“In our sample, better measurement of psychotic symptoms did not improve prediction, but better measurement of psychomotor symptoms did seem to be valuable,” according to the psychiatrist.
 

Protection against ECT’s cognitive side effects?

Dr. van Diermen and colleagues assessed short- and long-term changes in global cognitive functioning in 65 consecutive patients treated with ECT for a major depressive episode by administering the Montreal Cognitive Assessment (MoCA) at baseline, before the third ECT session, and 1 week, 3 months, and 6 months after completing their treatment course.

During ECT, the investigators documented a limited decrease in cognitive functioning at the group level, which rebounded during the 6 months after ECT. But although there was no significant difference between MoCA scores at baseline and 6 months follow-up after ECT in the overall group of study participants, that doesn’t tell the full story. Six months after completing their course of ECT, 18% of patients demonstrated improved cognitive functioning, compared with baseline, but 8% had significantly worse cognitive functioning than pretreatment.

“Saying that ECT has no cognitive effects seems to be somewhat wrong to me. It has cognitive effects for certain people, and it will be interesting to know which people,” Dr. van Diermen said.

In what she termed “a very, very preliminary analysis,” she found that the patients with psychotic or melancholic depression were markedly less likely to have long-term cognitive impairment as defined by a worse MoCA score, compared with baseline, both at 6 months and one or more intermediate time points. Only 1 of 31 patients with psychotic depression fell into that poor cognitive outcome category, as did 4 patients with melancholic depression, compared with 12 patients without psychotic depression and 9 without melancholic depression. This, Dr. van Diermen believes, is the first report of an apparent protective effect of melancholic or psychotic depression against ECT-induced long-term cognitive worsening.

“Replication of our results is definitely necessary in larger patient samples,” she cautioned.

Dr. van Diermen reported having no financial conflicts regarding her presentation.

[email protected]

SOURCE: van Diermen L. ECNP 2020, Session EDU03.

Irritability appears to be a potent independent predictor of increased risk for suicidality in children and adolescents with ADHD, Tomer Levy, MD, said at the virtual congress of the European College of Neuropsychopharmacology.

While there is ample evidence that ADHD is associated with increased suicidality, Dr. Levy’s recent study involving 1,516 youths aged 6-17 years attending an outpatient ADHD clinic demonstrated that this increased risk is mediated by depression and irritability in roughly equal measures. Moreover, upon controlling for those two factors in a multivariate analysis, ADHD symptoms, per se, had no direct effect on risk of suicidality as defined by suidical ideation, attempts, or self-harm.

The clinical take-home message is that assessing irritability, as well as depression, may bolster an estimate of suicidality and help in managing suicidal risk in ADHD, according to Dr. Levy, a child and adolescent psychiatrist at the Hospital for Sick Children, Toronto, and head of behavioral regulation services at the Geha Mental Health Center in Petah Tikva, Israel.

The study included separate parent- and teacher-structured reports of the youths’ ADHD symptoms, suicidality, depression, irritability, and anxiety. Parents reported suicidality in 12.1% of the pediatric patients, significantly higher than the 3.8% rate reported by teachers.

In multivariate analyses, parent-reported depression accounted for 39.1% of the association between ADHD symptoms and suicidality, while irritability symptoms mediated 36.8% of the total effect. In the teachers’ reports, depression and irritability symptoms accounted for 45.3% and 38.4% of the association. Anxiety symptoms mediated 19% of the relationship between ADHD and suicidality by parental report but had no significant impact on the association according to teacher report in the recently published study.

Dr. Levy noted that, in the DSM-5, irritability cuts across diagnostic categories. It is not only a core dimension of ADHD, but of the other externalizing disorders – conduct disorder and oppositional defiant disorder – as well, and also of neurodevelopmental, internalizing, and stress-related disorders.

Interventional studies aimed at dampening irritability as a potential strategy to reduce suicidality haven’t yet been done, but they deserve research priority status, in Dr. Levy’s view. Numerous functional dimensions that influence irritability are potential targets, including aggression, negative affect, low tolerance of frustration, skewed threat perception, and impaired self-regulation, according to the psychiatrist.

Most suicidal youths are attempting to cope with mental disorders. The most prevalent of these are major depressive disorder and dysthymia, followed by externalizing disorders. And among the externalizing disorders, conduct disorder stands out in terms of the magnitude of associated suicidality risk. In a large Taiwanese national study including 3,711 adolescents with conduct disorder and 14,844 age- and sex-matched controls, conduct disorder was associated with an adjusted 5.17-fold increased risk of subsequent suicide attempts over the next 10 years in a multivariate regression analysis adjusted for other psychiatric comorbidities and demographics.

In addition to depression, irritability symptoms, and conduct problems, other risk factors that should be part of a suicidality assessment in children and adolescents with ADHD include substance use, anxiety, poor family support, and bullying and/or being bullied. But, perhaps surprisingly, not impulsivity, Dr. Levy said.

“There is a widely held perception that impulsivity imparts a risk for suicidality, and especially in the transition from ideation to attempt. However, more recent evidence fails to show a convincing association,” according to Dr. Levy.

He reported having no financial conflicts regarding his presentation.

[email protected]

SOURCE: Levy T. ECNP 2020, Session EDU.02.

Irritability appears to be a potent independent predictor of increased risk for suicidality in children and adolescents with ADHD, Tomer Levy, MD, said at the virtual congress of the European College of Neuropsychopharmacology.

While there is ample evidence that ADHD is associated with increased suicidality, Dr. Levy’s recent study involving 1,516 youths aged 6-17 years attending an outpatient ADHD clinic demonstrated that this increased risk is mediated by depression and irritability in roughly equal measures. Moreover, upon controlling for those two factors in a multivariate analysis, ADHD symptoms, per se, had no direct effect on risk of suicidality as defined by suidical ideation, attempts, or self-harm.

The clinical take-home message is that assessing irritability, as well as depression, may bolster an estimate of suicidality and help in managing suicidal risk in ADHD, according to Dr. Levy, a child and adolescent psychiatrist at the Hospital for Sick Children, Toronto, and head of behavioral regulation services at the Geha Mental Health Center in Petah Tikva, Israel.

The study included separate parent- and teacher-structured reports of the youths’ ADHD symptoms, suicidality, depression, irritability, and anxiety. Parents reported suicidality in 12.1% of the pediatric patients, significantly higher than the 3.8% rate reported by teachers.

In multivariate analyses, parent-reported depression accounted for 39.1% of the association between ADHD symptoms and suicidality, while irritability symptoms mediated 36.8% of the total effect. In the teachers’ reports, depression and irritability symptoms accounted for 45.3% and 38.4% of the association. Anxiety symptoms mediated 19% of the relationship between ADHD and suicidality by parental report but had no significant impact on the association according to teacher report in the recently published study.

Dr. Levy noted that, in the DSM-5, irritability cuts across diagnostic categories. It is not only a core dimension of ADHD, but of the other externalizing disorders – conduct disorder and oppositional defiant disorder – as well, and also of neurodevelopmental, internalizing, and stress-related disorders.

Interventional studies aimed at dampening irritability as a potential strategy to reduce suicidality haven’t yet been done, but they deserve research priority status, in Dr. Levy’s view. Numerous functional dimensions that influence irritability are potential targets, including aggression, negative affect, low tolerance of frustration, skewed threat perception, and impaired self-regulation, according to the psychiatrist.

Most suicidal youths are attempting to cope with mental disorders. The most prevalent of these are major depressive disorder and dysthymia, followed by externalizing disorders. And among the externalizing disorders, conduct disorder stands out in terms of the magnitude of associated suicidality risk. In a large Taiwanese national study including 3,711 adolescents with conduct disorder and 14,844 age- and sex-matched controls, conduct disorder was associated with an adjusted 5.17-fold increased risk of subsequent suicide attempts over the next 10 years in a multivariate regression analysis adjusted for other psychiatric comorbidities and demographics.

In addition to depression, irritability symptoms, and conduct problems, other risk factors that should be part of a suicidality assessment in children and adolescents with ADHD include substance use, anxiety, poor family support, and bullying and/or being bullied. But, perhaps surprisingly, not impulsivity, Dr. Levy said.

“There is a widely held perception that impulsivity imparts a risk for suicidality, and especially in the transition from ideation to attempt. However, more recent evidence fails to show a convincing association,” according to Dr. Levy.

He reported having no financial conflicts regarding his presentation.

[email protected]

SOURCE: Levy T. ECNP 2020, Session EDU.02.

Irritability appears to be a potent independent predictor of increased risk for suicidality in children and adolescents with ADHD, Tomer Levy, MD, said at the virtual congress of the European College of Neuropsychopharmacology.

While there is ample evidence that ADHD is associated with increased suicidality, Dr. Levy’s recent study involving 1,516 youths aged 6-17 years attending an outpatient ADHD clinic demonstrated that this increased risk is mediated by depression and irritability in roughly equal measures. Moreover, upon controlling for those two factors in a multivariate analysis, ADHD symptoms, per se, had no direct effect on risk of suicidality as defined by suidical ideation, attempts, or self-harm.

The clinical take-home message is that assessing irritability, as well as depression, may bolster an estimate of suicidality and help in managing suicidal risk in ADHD, according to Dr. Levy, a child and adolescent psychiatrist at the Hospital for Sick Children, Toronto, and head of behavioral regulation services at the Geha Mental Health Center in Petah Tikva, Israel.

The study included separate parent- and teacher-structured reports of the youths’ ADHD symptoms, suicidality, depression, irritability, and anxiety. Parents reported suicidality in 12.1% of the pediatric patients, significantly higher than the 3.8% rate reported by teachers.

In multivariate analyses, parent-reported depression accounted for 39.1% of the association between ADHD symptoms and suicidality, while irritability symptoms mediated 36.8% of the total effect. In the teachers’ reports, depression and irritability symptoms accounted for 45.3% and 38.4% of the association. Anxiety symptoms mediated 19% of the relationship between ADHD and suicidality by parental report but had no significant impact on the association according to teacher report in the recently published study.

Dr. Levy noted that, in the DSM-5, irritability cuts across diagnostic categories. It is not only a core dimension of ADHD, but of the other externalizing disorders – conduct disorder and oppositional defiant disorder – as well, and also of neurodevelopmental, internalizing, and stress-related disorders.

Interventional studies aimed at dampening irritability as a potential strategy to reduce suicidality haven’t yet been done, but they deserve research priority status, in Dr. Levy’s view. Numerous functional dimensions that influence irritability are potential targets, including aggression, negative affect, low tolerance of frustration, skewed threat perception, and impaired self-regulation, according to the psychiatrist.

Most suicidal youths are attempting to cope with mental disorders. The most prevalent of these are major depressive disorder and dysthymia, followed by externalizing disorders. And among the externalizing disorders, conduct disorder stands out in terms of the magnitude of associated suicidality risk. In a large Taiwanese national study including 3,711 adolescents with conduct disorder and 14,844 age- and sex-matched controls, conduct disorder was associated with an adjusted 5.17-fold increased risk of subsequent suicide attempts over the next 10 years in a multivariate regression analysis adjusted for other psychiatric comorbidities and demographics.

In addition to depression, irritability symptoms, and conduct problems, other risk factors that should be part of a suicidality assessment in children and adolescents with ADHD include substance use, anxiety, poor family support, and bullying and/or being bullied. But, perhaps surprisingly, not impulsivity, Dr. Levy said.

“There is a widely held perception that impulsivity imparts a risk for suicidality, and especially in the transition from ideation to attempt. However, more recent evidence fails to show a convincing association,” according to Dr. Levy.

He reported having no financial conflicts regarding his presentation.

[email protected]

SOURCE: Levy T. ECNP 2020, Session EDU.02.

General anesthesia for ECT gets short shrift in the psychiatric literature, yet it’s an indispensable part of the procedure, with a major impact on its safety and outcomes, Alexander Sartorius, MD, asserted at the virtual congress of the European College of Neuropsychopharmacology.

Just how neglected is the topic?

“The two bibles of ECT – the American Psychiatric Association’s ‘The Practice of Electroconvulsive Therapy’ and Richard Abrams’s ‘Electroconvulsive Therapy,’ contain only three pages on anesthesia out of several hundred pages,” noted Dr. Sartorius, a psychiatrist at the Central Institute of Mental Health in Mannheim, Germany.

Dr. Sartorius, who has published extensively on the management of general anesthesia in ECT, offered fresh insights into its optimization. He also shared how to swiftly identify and deal with its main side effects.

General anesthesia is an essential part of ECT for only one reason: Not to spare the patient from pain or trauma, as is widely supposed, but simply to avoid awareness of the muscle relaxant that’s given to prevent bone fractures and other injuries caused by motor seizure, the psychiatrist explained.

Four anesthetic agents traditionally used for ECT have fallen by the wayside. The two barbiturates, thiopental and methohexital, have problematic anticonvulsant properties that complicate their use in a procedure whose whole purpose is to induce a seizure. Plus, they have black-box warnings in some countries. Etomidate, in contrast, has no anticonvulsant effect; however, anesthesiologists are increasingly leery of the drug. A single dose completely suppresses the hypothalamic-pituitary-adrenal axis for more than 24 hours, and mounting evidence suggests that etomidate may be associated with increased mortality.

Dr. Sartorius is a fan of ketofol, a combination of two anesthetic agents – ketamine and propofol – that provide rapid onset and cessation of action, pharmacokinetic predictability, synergistic efficacy, and minimal adverse effects when the two drugs are given in doses lower than standard as monotherapy.

Propofol has attractive qualities as an anesthetic, but it is a very potent anticonvulsant with an adverse effect on seizure quality and duration. When used alone for general anesthesia in ECT, a higher stimulation dose is often necessary to achieve adequate seizure quality, which in turn may produce worse cognitive side effects. In contrast, ketamine, which is listed as an essential drug by the World Health Organization, has no anticonvulsive effects.

“My conclusion about ketamine alone is it has less side effects than feared, and it’s probably not more but definitely not less effective than the grand old four anesthetic agents,” Dr. Sartorius said.

Plus, ketamine shows promise as an antidepressant agent in and of itself. Moreover, the fact that patients require a lower ECT stimulation dose while under the influence of ketamine could result in fewer cognitive side effects, although that’s conjecture at this point, he added.

Ketofol is often administered in a 1:1 ratio of propofol to ketamine. That’s not optimum for each individual patient undergoing ECT, as in many cases it results in so much propofol that seizure quality is diminished, in Dr. Sartorius’s experience. He, therefore, recently published a retrospective study of 52 patients who received 919 ECT sessions with empirically determined doses of S-ketamine plus propofol for anesthesia. The endpoints were time in the recovery room and seizure duration and quality. Seizure quality was assessed as a composite of the ratio of duration of motor response to EEG seizure duration, peak heart rate, midictal amplitude, maximal interhemispheric coherence, and postictal suppression index.

The optimal S-ketamine/propofol ratio in terms of seizure quality was 1.52:1, with a mean relative dose of 0.72 mg/kg of S-ketamine and 0.54 mg/kg of propofol.

His team uses only the S-enantiomer of ketamine, not the racemic mixture known as ketamine, but his study results would translate to a 3:1 ratio of racemic ketamine to propofol, Dr. Sartorius said.

Time in the recovery room was dependent upon return of cardiorespiratory function and orientation status to baseline pre-ECT levels. Longer recovery room time proved to be significantly related to older age. The S-ketamine dose wasn’t a significant factor.

Propofol was injected prior to S-ketamine in all patients. This was followed 1-2 minutes later by administration of succinylcholine as a muscle relaxant. It’s important to then wait for at least another 2-3 minutes before delivering the ECT stimulation. Dr. Sartorius and others have demonstrated that waiting at least 4 minutes between anesthesia induction and delivery of the ECT charge results in a better-quality seizure.

“We have a timer running so we can be sure to wait longer than 4 minutes. That’s a large advantage if you want to reduce the anticonvulsant property of propofol,” he explained.
 

Anesthesia-related side effects

Dr. Sartorius addressed postictal agitation syndrome, postanesthetic shivering, cardiac arrhythmias, and hypersalivation.

Postictal agitation syndrome: The deeper the level of sedation, the less likely this complication. Historically, in ECT without anesthesia, the incidence of postictal agitation was as high as 50%. At the center where Dr. Sartorius works, it’s 2%-3%. The use of intraprocedural bispectral index monitoring of the achieved deepest level of sedation allows highly accurate prediction of postictal agitation.

“Do not restrain,” he advised. “Patients are aware of this problematic situation. You have to keep everything calm and use the least possible amount of physical limitation. The good thing is that it’s self-limited within 20 minutes in most cases. But in severe cases you have to escalate staff immediately, and you may want to use 10 mg of IV diazepam. The most important message is you have to increase the dose of your anesthetic with the next ECT; a lower dose of anesthetic is not the solution.”

It is also important to watch for these possible complications:

• Postanesthetic shivering: This is a rare but potentially fatal complication. It’s important to be familiar with the grading system, and to recognize that grade 3 or 4 post-anesthetic shivering requires treatment. “The treatment of choice is clonidine. That should always be with you when you do ECT,” Dr. Sartorius observed.
• Cardiac arrhythmias: “ECT is a proarrhythmic intervention; don’t forget that,” he said.
• Poststimulation asystole: This occurs in more than half of treated patients. It’s caused by the current, not the seizure, and it stops within a few seconds after the current halts. If the asystoles bother the patient, try switching to bifrontal electrode placement. Right unilateral stimulation has been shown to increase the likelihood of asystole by 207-fold, compared with bifrontal stimulation.
• Tachycardia: This is another common complication of ECT. It responds well to a short-acting beta-blocker.
• Hypersalivation: The treatment of choice is glycopyrrolate, a muscarinic receptor antagonist that doesn’t cross the blood-brain barrier.

Dr. Sartorius reported having no financial conflicts regarding his presentation.

[email protected]

SOURCE: Sartorius A et al. ECNP 2020, Session EDU03.02.

General anesthesia for ECT gets short shrift in the psychiatric literature, yet it’s an indispensable part of the procedure, with a major impact on its safety and outcomes, Alexander Sartorius, MD, asserted at the virtual congress of the European College of Neuropsychopharmacology.

Just how neglected is the topic?

“The two bibles of ECT – the American Psychiatric Association’s ‘The Practice of Electroconvulsive Therapy’ and Richard Abrams’s ‘Electroconvulsive Therapy,’ contain only three pages on anesthesia out of several hundred pages,” noted Dr. Sartorius, a psychiatrist at the Central Institute of Mental Health in Mannheim, Germany.

Dr. Sartorius, who has published extensively on the management of general anesthesia in ECT, offered fresh insights into its optimization. He also shared how to swiftly identify and deal with its main side effects.

General anesthesia is an essential part of ECT for only one reason: Not to spare the patient from pain or trauma, as is widely supposed, but simply to avoid awareness of the muscle relaxant that’s given to prevent bone fractures and other injuries caused by motor seizure, the psychiatrist explained.

Four anesthetic agents traditionally used for ECT have fallen by the wayside. The two barbiturates, thiopental and methohexital, have problematic anticonvulsant properties that complicate their use in a procedure whose whole purpose is to induce a seizure. Plus, they have black-box warnings in some countries. Etomidate, in contrast, has no anticonvulsant effect; however, anesthesiologists are increasingly leery of the drug. A single dose completely suppresses the hypothalamic-pituitary-adrenal axis for more than 24 hours, and mounting evidence suggests that etomidate may be associated with increased mortality.

Dr. Sartorius is a fan of ketofol, a combination of two anesthetic agents – ketamine and propofol – that provide rapid onset and cessation of action, pharmacokinetic predictability, synergistic efficacy, and minimal adverse effects when the two drugs are given in doses lower than standard as monotherapy.

Propofol has attractive qualities as an anesthetic, but it is a very potent anticonvulsant with an adverse effect on seizure quality and duration. When used alone for general anesthesia in ECT, a higher stimulation dose is often necessary to achieve adequate seizure quality, which in turn may produce worse cognitive side effects. In contrast, ketamine, which is listed as an essential drug by the World Health Organization, has no anticonvulsive effects.

“My conclusion about ketamine alone is it has less side effects than feared, and it’s probably not more but definitely not less effective than the grand old four anesthetic agents,” Dr. Sartorius said.

Plus, ketamine shows promise as an antidepressant agent in and of itself. Moreover, the fact that patients require a lower ECT stimulation dose while under the influence of ketamine could result in fewer cognitive side effects, although that’s conjecture at this point, he added.

Ketofol is often administered in a 1:1 ratio of propofol to ketamine. That’s not optimum for each individual patient undergoing ECT, as in many cases it results in so much propofol that seizure quality is diminished, in Dr. Sartorius’s experience. He, therefore, recently published a retrospective study of 52 patients who received 919 ECT sessions with empirically determined doses of S-ketamine plus propofol for anesthesia. The endpoints were time in the recovery room and seizure duration and quality. Seizure quality was assessed as a composite of the ratio of duration of motor response to EEG seizure duration, peak heart rate, midictal amplitude, maximal interhemispheric coherence, and postictal suppression index.

The optimal S-ketamine/propofol ratio in terms of seizure quality was 1.52:1, with a mean relative dose of 0.72 mg/kg of S-ketamine and 0.54 mg/kg of propofol.

His team uses only the S-enantiomer of ketamine, not the racemic mixture known as ketamine, but his study results would translate to a 3:1 ratio of racemic ketamine to propofol, Dr. Sartorius said.

Time in the recovery room was dependent upon return of cardiorespiratory function and orientation status to baseline pre-ECT levels. Longer recovery room time proved to be significantly related to older age. The S-ketamine dose wasn’t a significant factor.

Propofol was injected prior to S-ketamine in all patients. This was followed 1-2 minutes later by administration of succinylcholine as a muscle relaxant. It’s important to then wait for at least another 2-3 minutes before delivering the ECT stimulation. Dr. Sartorius and others have demonstrated that waiting at least 4 minutes between anesthesia induction and delivery of the ECT charge results in a better-quality seizure.

“We have a timer running so we can be sure to wait longer than 4 minutes. That’s a large advantage if you want to reduce the anticonvulsant property of propofol,” he explained.
 

Anesthesia-related side effects

Dr. Sartorius addressed postictal agitation syndrome, postanesthetic shivering, cardiac arrhythmias, and hypersalivation.

Postictal agitation syndrome: The deeper the level of sedation, the less likely this complication. Historically, in ECT without anesthesia, the incidence of postictal agitation was as high as 50%. At the center where Dr. Sartorius works, it’s 2%-3%. The use of intraprocedural bispectral index monitoring of the achieved deepest level of sedation allows highly accurate prediction of postictal agitation.

“Do not restrain,” he advised. “Patients are aware of this problematic situation. You have to keep everything calm and use the least possible amount of physical limitation. The good thing is that it’s self-limited within 20 minutes in most cases. But in severe cases you have to escalate staff immediately, and you may want to use 10 mg of IV diazepam. The most important message is you have to increase the dose of your anesthetic with the next ECT; a lower dose of anesthetic is not the solution.”

It is also important to watch for these possible complications:

• Postanesthetic shivering: This is a rare but potentially fatal complication. It’s important to be familiar with the grading system, and to recognize that grade 3 or 4 post-anesthetic shivering requires treatment. “The treatment of choice is clonidine. That should always be with you when you do ECT,” Dr. Sartorius observed.
• Cardiac arrhythmias: “ECT is a proarrhythmic intervention; don’t forget that,” he said.
• Poststimulation asystole: This occurs in more than half of treated patients. It’s caused by the current, not the seizure, and it stops within a few seconds after the current halts. If the asystoles bother the patient, try switching to bifrontal electrode placement. Right unilateral stimulation has been shown to increase the likelihood of asystole by 207-fold, compared with bifrontal stimulation.
• Tachycardia: This is another common complication of ECT. It responds well to a short-acting beta-blocker.
• Hypersalivation: The treatment of choice is glycopyrrolate, a muscarinic receptor antagonist that doesn’t cross the blood-brain barrier.

Dr. Sartorius reported having no financial conflicts regarding his presentation.

[email protected]

SOURCE: Sartorius A et al. ECNP 2020, Session EDU03.02.

General anesthesia for ECT gets short shrift in the psychiatric literature, yet it’s an indispensable part of the procedure, with a major impact on its safety and outcomes, Alexander Sartorius, MD, asserted at the virtual congress of the European College of Neuropsychopharmacology.

Just how neglected is the topic?

“The two bibles of ECT – the American Psychiatric Association’s ‘The Practice of Electroconvulsive Therapy’ and Richard Abrams’s ‘Electroconvulsive Therapy,’ contain only three pages on anesthesia out of several hundred pages,” noted Dr. Sartorius, a psychiatrist at the Central Institute of Mental Health in Mannheim, Germany.

Dr. Sartorius, who has published extensively on the management of general anesthesia in ECT, offered fresh insights into its optimization. He also shared how to swiftly identify and deal with its main side effects.

General anesthesia is an essential part of ECT for only one reason: Not to spare the patient from pain or trauma, as is widely supposed, but simply to avoid awareness of the muscle relaxant that’s given to prevent bone fractures and other injuries caused by motor seizure, the psychiatrist explained.

Four anesthetic agents traditionally used for ECT have fallen by the wayside. The two barbiturates, thiopental and methohexital, have problematic anticonvulsant properties that complicate their use in a procedure whose whole purpose is to induce a seizure. Plus, they have black-box warnings in some countries. Etomidate, in contrast, has no anticonvulsant effect; however, anesthesiologists are increasingly leery of the drug. A single dose completely suppresses the hypothalamic-pituitary-adrenal axis for more than 24 hours, and mounting evidence suggests that etomidate may be associated with increased mortality.

Dr. Sartorius is a fan of ketofol, a combination of two anesthetic agents – ketamine and propofol – that provide rapid onset and cessation of action, pharmacokinetic predictability, synergistic efficacy, and minimal adverse effects when the two drugs are given in doses lower than standard as monotherapy.

Propofol has attractive qualities as an anesthetic, but it is a very potent anticonvulsant with an adverse effect on seizure quality and duration. When used alone for general anesthesia in ECT, a higher stimulation dose is often necessary to achieve adequate seizure quality, which in turn may produce worse cognitive side effects. In contrast, ketamine, which is listed as an essential drug by the World Health Organization, has no anticonvulsive effects.

“My conclusion about ketamine alone is it has less side effects than feared, and it’s probably not more but definitely not less effective than the grand old four anesthetic agents,” Dr. Sartorius said.

Plus, ketamine shows promise as an antidepressant agent in and of itself. Moreover, the fact that patients require a lower ECT stimulation dose while under the influence of ketamine could result in fewer cognitive side effects, although that’s conjecture at this point, he added.

Ketofol is often administered in a 1:1 ratio of propofol to ketamine. That’s not optimum for each individual patient undergoing ECT, as in many cases it results in so much propofol that seizure quality is diminished, in Dr. Sartorius’s experience. He, therefore, recently published a retrospective study of 52 patients who received 919 ECT sessions with empirically determined doses of S-ketamine plus propofol for anesthesia. The endpoints were time in the recovery room and seizure duration and quality. Seizure quality was assessed as a composite of the ratio of duration of motor response to EEG seizure duration, peak heart rate, midictal amplitude, maximal interhemispheric coherence, and postictal suppression index.

The optimal S-ketamine/propofol ratio in terms of seizure quality was 1.52:1, with a mean relative dose of 0.72 mg/kg of S-ketamine and 0.54 mg/kg of propofol.

His team uses only the S-enantiomer of ketamine, not the racemic mixture known as ketamine, but his study results would translate to a 3:1 ratio of racemic ketamine to propofol, Dr. Sartorius said.

Time in the recovery room was dependent upon return of cardiorespiratory function and orientation status to baseline pre-ECT levels. Longer recovery room time proved to be significantly related to older age. The S-ketamine dose wasn’t a significant factor.

Propofol was injected prior to S-ketamine in all patients. This was followed 1-2 minutes later by administration of succinylcholine as a muscle relaxant. It’s important to then wait for at least another 2-3 minutes before delivering the ECT stimulation. Dr. Sartorius and others have demonstrated that waiting at least 4 minutes between anesthesia induction and delivery of the ECT charge results in a better-quality seizure.

“We have a timer running so we can be sure to wait longer than 4 minutes. That’s a large advantage if you want to reduce the anticonvulsant property of propofol,” he explained.
 

Anesthesia-related side effects

Dr. Sartorius addressed postictal agitation syndrome, postanesthetic shivering, cardiac arrhythmias, and hypersalivation.

Postictal agitation syndrome: The deeper the level of sedation, the less likely this complication. Historically, in ECT without anesthesia, the incidence of postictal agitation was as high as 50%. At the center where Dr. Sartorius works, it’s 2%-3%. The use of intraprocedural bispectral index monitoring of the achieved deepest level of sedation allows highly accurate prediction of postictal agitation.

“Do not restrain,” he advised. “Patients are aware of this problematic situation. You have to keep everything calm and use the least possible amount of physical limitation. The good thing is that it’s self-limited within 20 minutes in most cases. But in severe cases you have to escalate staff immediately, and you may want to use 10 mg of IV diazepam. The most important message is you have to increase the dose of your anesthetic with the next ECT; a lower dose of anesthetic is not the solution.”

It is also important to watch for these possible complications:

• Postanesthetic shivering: This is a rare but potentially fatal complication. It’s important to be familiar with the grading system, and to recognize that grade 3 or 4 post-anesthetic shivering requires treatment. “The treatment of choice is clonidine. That should always be with you when you do ECT,” Dr. Sartorius observed.
• Cardiac arrhythmias: “ECT is a proarrhythmic intervention; don’t forget that,” he said.
• Poststimulation asystole: This occurs in more than half of treated patients. It’s caused by the current, not the seizure, and it stops within a few seconds after the current halts. If the asystoles bother the patient, try switching to bifrontal electrode placement. Right unilateral stimulation has been shown to increase the likelihood of asystole by 207-fold, compared with bifrontal stimulation.
• Tachycardia: This is another common complication of ECT. It responds well to a short-acting beta-blocker.
• Hypersalivation: The treatment of choice is glycopyrrolate, a muscarinic receptor antagonist that doesn’t cross the blood-brain barrier.

Dr. Sartorius reported having no financial conflicts regarding his presentation.

[email protected]

SOURCE: Sartorius A et al. ECNP 2020, Session EDU03.02.