Ted Bosworth

NATIONAL HARBOR, MD – Data presented at the 2020 CRT meeting, sponsored by MedStar Heart & Vascular Institute, show that transcatheter aortic valve replacement (TAVR) is safe and effective, at least in the short term, for low-risk patients with bicuspid aortic stenosis, which addresses a data gap.

Ted Bosworth/MDedge News

In an investigator-driven prospective study, called LRT, there was no mortality, no myocardial infarctions (MI), and no disabling strokes 30 days after the procedure, according to Ronald Waksman, MD, associate director of cardiology at Medstar Heart Institute in Washington.

TAVR was approved in 2019 for low-risk patients with symptomatic severe aortic stenosis regardless of aortic valve morphology, but the pivotal industry-led trials only enrolled patients with tricuspid valves, excluding the bicuspid population, according to Dr. Waksman.

However, bicuspid patients were enrolled in the investigator-led LRT study. The 1-year results with tricuspid values have been published previously (JACC Cardiovasc Interv. 2019;12:901-7), but new data from this same study provides the first prospective evaluation in low-risk bicuspid patients.

The LRT enrollment criteria were the same for the bicuspid patients as they were for those enrolled with tricuspid valves. These included a low surgical risk, defined as a Society of Thoracic Surgeons (STS) score of 3 or less; no high-risk criteria independent of STS score; and eligibility for a transfemoral percutaneous procedure. Patients were permitted to undergo TAVR with any commercially available device.

The 61 patients enrolled from August 2016 to September 2019 were compared at 30 days of follow-up with 211 low-risk bicuspid patients undergoing surgical aortic valve replacement (SAVR). Propensity matched, the two groups had generally similar baseline characteristics with some exceptions. Relative to the SAVR group, the TAVR group had an older median age (68.6 vs. 63.4 years) and a lower proportion of males (42.6% vs. 65.7%) and a lower proportion with New York Heart Association heart failure of class III or higher (15.8% vs. 24.6%).

For the primary outcome of all-cause mortality at 30 days, there were no deaths in the TAVR group versus one death in the SAVR group. TAVR was associated with a shorter length of stay (2.0 vs. 5.8 days) and a lower risk of new-onset atrial fibrillation (1.6% vs. 42.6%). However, pacemaker implantations were more common in the TAVR group (11.5% vs. 5.6%). There was one stroke in the TAVR group, but it was not disabling.

Following TAVR, there was one case of paravalvular leak, but it was of moderate severity, according to Dr. Waksman. Leaflet thrombosis in the form of hypoattenuated leaflet thickening (HALT), which occurred in 10.2% of patients; reduced leaflet motion (RELM), which occurred in 6.9%; and hypoattenuation affecting motion (HAM), which also occurred in 6.9%, was observed at 30 days following TAVR, but these have not so far been associated with any clinical consequences.

At baseline, only 4.9% of the bicuspid patients met criteria for NYHA class I function and 23% were in NYHA class III or higher. By 30 days, the proportion in NYHA class I had risen to 78.3%, and no patient was in NYHA class III or higher. Dr. Waksman characterized the improvement in hemodynamics – measured by mean aortic valve gradient and aortic valve area – as “excellent” at 30 days.

Further follow-up of bicuspid patients in the LRT study is needed to confirm long-term safety and efficacy, but Dr. Waksman indicated that the 30-day results are encouraging, in part because they show no greater risk of periprocedural complications than that observed in the tricuspid population.

NATIONAL HARBOR, MD – Data presented at the 2020 CRT meeting, sponsored by MedStar Heart & Vascular Institute, show that transcatheter aortic valve replacement (TAVR) is safe and effective, at least in the short term, for low-risk patients with bicuspid aortic stenosis, which addresses a data gap.

Ted Bosworth/MDedge News

In an investigator-driven prospective study, called LRT, there was no mortality, no myocardial infarctions (MI), and no disabling strokes 30 days after the procedure, according to Ronald Waksman, MD, associate director of cardiology at Medstar Heart Institute in Washington.

TAVR was approved in 2019 for low-risk patients with symptomatic severe aortic stenosis regardless of aortic valve morphology, but the pivotal industry-led trials only enrolled patients with tricuspid valves, excluding the bicuspid population, according to Dr. Waksman.

However, bicuspid patients were enrolled in the investigator-led LRT study. The 1-year results with tricuspid values have been published previously (JACC Cardiovasc Interv. 2019;12:901-7), but new data from this same study provides the first prospective evaluation in low-risk bicuspid patients.

The LRT enrollment criteria were the same for the bicuspid patients as they were for those enrolled with tricuspid valves. These included a low surgical risk, defined as a Society of Thoracic Surgeons (STS) score of 3 or less; no high-risk criteria independent of STS score; and eligibility for a transfemoral percutaneous procedure. Patients were permitted to undergo TAVR with any commercially available device.

The 61 patients enrolled from August 2016 to September 2019 were compared at 30 days of follow-up with 211 low-risk bicuspid patients undergoing surgical aortic valve replacement (SAVR). Propensity matched, the two groups had generally similar baseline characteristics with some exceptions. Relative to the SAVR group, the TAVR group had an older median age (68.6 vs. 63.4 years) and a lower proportion of males (42.6% vs. 65.7%) and a lower proportion with New York Heart Association heart failure of class III or higher (15.8% vs. 24.6%).

For the primary outcome of all-cause mortality at 30 days, there were no deaths in the TAVR group versus one death in the SAVR group. TAVR was associated with a shorter length of stay (2.0 vs. 5.8 days) and a lower risk of new-onset atrial fibrillation (1.6% vs. 42.6%). However, pacemaker implantations were more common in the TAVR group (11.5% vs. 5.6%). There was one stroke in the TAVR group, but it was not disabling.

Following TAVR, there was one case of paravalvular leak, but it was of moderate severity, according to Dr. Waksman. Leaflet thrombosis in the form of hypoattenuated leaflet thickening (HALT), which occurred in 10.2% of patients; reduced leaflet motion (RELM), which occurred in 6.9%; and hypoattenuation affecting motion (HAM), which also occurred in 6.9%, was observed at 30 days following TAVR, but these have not so far been associated with any clinical consequences.

At baseline, only 4.9% of the bicuspid patients met criteria for NYHA class I function and 23% were in NYHA class III or higher. By 30 days, the proportion in NYHA class I had risen to 78.3%, and no patient was in NYHA class III or higher. Dr. Waksman characterized the improvement in hemodynamics – measured by mean aortic valve gradient and aortic valve area – as “excellent” at 30 days.

Further follow-up of bicuspid patients in the LRT study is needed to confirm long-term safety and efficacy, but Dr. Waksman indicated that the 30-day results are encouraging, in part because they show no greater risk of periprocedural complications than that observed in the tricuspid population.

NATIONAL HARBOR, MD – Data presented at the 2020 CRT meeting, sponsored by MedStar Heart & Vascular Institute, show that transcatheter aortic valve replacement (TAVR) is safe and effective, at least in the short term, for low-risk patients with bicuspid aortic stenosis, which addresses a data gap.

Ted Bosworth/MDedge News

In an investigator-driven prospective study, called LRT, there was no mortality, no myocardial infarctions (MI), and no disabling strokes 30 days after the procedure, according to Ronald Waksman, MD, associate director of cardiology at Medstar Heart Institute in Washington.

TAVR was approved in 2019 for low-risk patients with symptomatic severe aortic stenosis regardless of aortic valve morphology, but the pivotal industry-led trials only enrolled patients with tricuspid valves, excluding the bicuspid population, according to Dr. Waksman.

However, bicuspid patients were enrolled in the investigator-led LRT study. The 1-year results with tricuspid values have been published previously (JACC Cardiovasc Interv. 2019;12:901-7), but new data from this same study provides the first prospective evaluation in low-risk bicuspid patients.

The LRT enrollment criteria were the same for the bicuspid patients as they were for those enrolled with tricuspid valves. These included a low surgical risk, defined as a Society of Thoracic Surgeons (STS) score of 3 or less; no high-risk criteria independent of STS score; and eligibility for a transfemoral percutaneous procedure. Patients were permitted to undergo TAVR with any commercially available device.

The 61 patients enrolled from August 2016 to September 2019 were compared at 30 days of follow-up with 211 low-risk bicuspid patients undergoing surgical aortic valve replacement (SAVR). Propensity matched, the two groups had generally similar baseline characteristics with some exceptions. Relative to the SAVR group, the TAVR group had an older median age (68.6 vs. 63.4 years) and a lower proportion of males (42.6% vs. 65.7%) and a lower proportion with New York Heart Association heart failure of class III or higher (15.8% vs. 24.6%).

For the primary outcome of all-cause mortality at 30 days, there were no deaths in the TAVR group versus one death in the SAVR group. TAVR was associated with a shorter length of stay (2.0 vs. 5.8 days) and a lower risk of new-onset atrial fibrillation (1.6% vs. 42.6%). However, pacemaker implantations were more common in the TAVR group (11.5% vs. 5.6%). There was one stroke in the TAVR group, but it was not disabling.

Following TAVR, there was one case of paravalvular leak, but it was of moderate severity, according to Dr. Waksman. Leaflet thrombosis in the form of hypoattenuated leaflet thickening (HALT), which occurred in 10.2% of patients; reduced leaflet motion (RELM), which occurred in 6.9%; and hypoattenuation affecting motion (HAM), which also occurred in 6.9%, was observed at 30 days following TAVR, but these have not so far been associated with any clinical consequences.

At baseline, only 4.9% of the bicuspid patients met criteria for NYHA class I function and 23% were in NYHA class III or higher. By 30 days, the proportion in NYHA class I had risen to 78.3%, and no patient was in NYHA class III or higher. Dr. Waksman characterized the improvement in hemodynamics – measured by mean aortic valve gradient and aortic valve area – as “excellent” at 30 days.

Further follow-up of bicuspid patients in the LRT study is needed to confirm long-term safety and efficacy, but Dr. Waksman indicated that the 30-day results are encouraging, in part because they show no greater risk of periprocedural complications than that observed in the tricuspid population.

Central centrifugal cicatricial alopecia (CCCA) appears to be distinguished from other scarring forms of alopecia by the predominance of CD4+ cells in the lymphocytic inflammatory infiltrate, according to a histopathological study of biopsy specimens.

“Evaluation of the T-cell infiltrate may be a useful way to distinguish CCCA from lichen planopilaris or frontal fibrosing alopecia in some cases when histopathological features alone cannot be used to definitely distinguish between them,” reported Alexandra Flamm, MD, Ata Moshiri, MD, and coauthors from the departments of dermatology and pathology, University of Pennsylvania, Philadelphia.

The histopathological features of CCCA have been characterized previously, but the goal of this study was to go further in piecing together the pathophysiology, they noted.

Horizontal sections of 4-mm punch biopsy specimens were examined from 18 black women with a known diagnosis of CCCA. Both affected and unaffected follicles were evaluated with attention to the number and percentage of CD1a+ Langerhans cells, CD3+, CD4+, and CD8+ lymphocytes.

In this series, the lymphocytic infiltrate in both the affected and unaffected follicles was predominantly composed of CD4+ cells. The perifollicular ratio for CD4+ to CD8+ cells in affected follicles was 5.3:1. It was only modestly lower in unaffected follicles (4.3:1) and in the intrafollicular space of affected follicles (2.5:1).

Affected follicles had a higher number of CD1a+ Langerhans cells than unaffected follicles. This finding suggests, as others have hypothesized, that the antigen-presenting Langerhans cells draw lymphocytes to the follicle, according to the investigators. Elevated numbers of Langerhans cells have also been reported in other forms of scarring alopecia, such as lichen planopilaris (LPP).

In the case of CCCA, CD1a+ Langerhans cells appear to localize to the hair follicle in response to stimulus such as an injury. The CD4+ cells that follow the Langerhans cells participate in an inflammatory reaction that drives follicle destruction. In addition to this damage and scarring, the inflammatory response is also likely to be disrupting the blood supply.

“Fibroplasia associated with follicular scarring displaces blood vessels away from the outer root sheath epithelium,” the authors explained. Ultimately, “the mucinous fibroplasia and perifollicular fibrosis may disrupt and fragment blood vessels in the fibrous sheath, leaving only small clusters of vessels more distant to the keratinocytes in the outer root sheath.”

Prior studies of scarring alopecia diseases, including LLP, frontal fibrosing alopecia (FFA), and keratosis follicularis spinulosa decalvans (KFSD), have typically described a predominantly CD8+ lymphocytic infiltrate. The evidence from this study that the infiltrate is CD4+ predominant in CCCA supports the conclusion that the pathophysiologic features of this type of alopecia are unique, according to the authors.

Work by others has associated CCCA with mutations in the PAD13 gene, which suggests a defect in the formation of hair shaft structure, but this may speak to susceptibility but not the mechanism of hair follicle damage. Rather, this study suggests that it is the concentration of a CD4+ predominant lymphocytic infiltrate in the perifollicular space that induces the pathological events.

For determining the fundamental cause of CCCA, “it will be important to determine what recruits the Langerhans cells to affected follicles,” the investigators suggested. Meanwhile, they expressed hope that the progress being made into decoding the pathogenesis of CCCA will lead to novel therapeutic strategies.

The authors did not list any disclosures. The funding source was listed as the Center for Scientific Review (Grant/Award).

SOURCE: Flamm A et al. J Cutan Pathol. 2020 Feb 18.doi: 10.1111/cup.13666.

Central centrifugal cicatricial alopecia (CCCA) appears to be distinguished from other scarring forms of alopecia by the predominance of CD4+ cells in the lymphocytic inflammatory infiltrate, according to a histopathological study of biopsy specimens.

“Evaluation of the T-cell infiltrate may be a useful way to distinguish CCCA from lichen planopilaris or frontal fibrosing alopecia in some cases when histopathological features alone cannot be used to definitely distinguish between them,” reported Alexandra Flamm, MD, Ata Moshiri, MD, and coauthors from the departments of dermatology and pathology, University of Pennsylvania, Philadelphia.

The histopathological features of CCCA have been characterized previously, but the goal of this study was to go further in piecing together the pathophysiology, they noted.

Horizontal sections of 4-mm punch biopsy specimens were examined from 18 black women with a known diagnosis of CCCA. Both affected and unaffected follicles were evaluated with attention to the number and percentage of CD1a+ Langerhans cells, CD3+, CD4+, and CD8+ lymphocytes.

In this series, the lymphocytic infiltrate in both the affected and unaffected follicles was predominantly composed of CD4+ cells. The perifollicular ratio for CD4+ to CD8+ cells in affected follicles was 5.3:1. It was only modestly lower in unaffected follicles (4.3:1) and in the intrafollicular space of affected follicles (2.5:1).

Affected follicles had a higher number of CD1a+ Langerhans cells than unaffected follicles. This finding suggests, as others have hypothesized, that the antigen-presenting Langerhans cells draw lymphocytes to the follicle, according to the investigators. Elevated numbers of Langerhans cells have also been reported in other forms of scarring alopecia, such as lichen planopilaris (LPP).

In the case of CCCA, CD1a+ Langerhans cells appear to localize to the hair follicle in response to stimulus such as an injury. The CD4+ cells that follow the Langerhans cells participate in an inflammatory reaction that drives follicle destruction. In addition to this damage and scarring, the inflammatory response is also likely to be disrupting the blood supply.

“Fibroplasia associated with follicular scarring displaces blood vessels away from the outer root sheath epithelium,” the authors explained. Ultimately, “the mucinous fibroplasia and perifollicular fibrosis may disrupt and fragment blood vessels in the fibrous sheath, leaving only small clusters of vessels more distant to the keratinocytes in the outer root sheath.”

Prior studies of scarring alopecia diseases, including LLP, frontal fibrosing alopecia (FFA), and keratosis follicularis spinulosa decalvans (KFSD), have typically described a predominantly CD8+ lymphocytic infiltrate. The evidence from this study that the infiltrate is CD4+ predominant in CCCA supports the conclusion that the pathophysiologic features of this type of alopecia are unique, according to the authors.

Work by others has associated CCCA with mutations in the PAD13 gene, which suggests a defect in the formation of hair shaft structure, but this may speak to susceptibility but not the mechanism of hair follicle damage. Rather, this study suggests that it is the concentration of a CD4+ predominant lymphocytic infiltrate in the perifollicular space that induces the pathological events.

For determining the fundamental cause of CCCA, “it will be important to determine what recruits the Langerhans cells to affected follicles,” the investigators suggested. Meanwhile, they expressed hope that the progress being made into decoding the pathogenesis of CCCA will lead to novel therapeutic strategies.

The authors did not list any disclosures. The funding source was listed as the Center for Scientific Review (Grant/Award).

SOURCE: Flamm A et al. J Cutan Pathol. 2020 Feb 18.doi: 10.1111/cup.13666.

Central centrifugal cicatricial alopecia (CCCA) appears to be distinguished from other scarring forms of alopecia by the predominance of CD4+ cells in the lymphocytic inflammatory infiltrate, according to a histopathological study of biopsy specimens.

“Evaluation of the T-cell infiltrate may be a useful way to distinguish CCCA from lichen planopilaris or frontal fibrosing alopecia in some cases when histopathological features alone cannot be used to definitely distinguish between them,” reported Alexandra Flamm, MD, Ata Moshiri, MD, and coauthors from the departments of dermatology and pathology, University of Pennsylvania, Philadelphia.

The histopathological features of CCCA have been characterized previously, but the goal of this study was to go further in piecing together the pathophysiology, they noted.

Horizontal sections of 4-mm punch biopsy specimens were examined from 18 black women with a known diagnosis of CCCA. Both affected and unaffected follicles were evaluated with attention to the number and percentage of CD1a+ Langerhans cells, CD3+, CD4+, and CD8+ lymphocytes.

In this series, the lymphocytic infiltrate in both the affected and unaffected follicles was predominantly composed of CD4+ cells. The perifollicular ratio for CD4+ to CD8+ cells in affected follicles was 5.3:1. It was only modestly lower in unaffected follicles (4.3:1) and in the intrafollicular space of affected follicles (2.5:1).

Affected follicles had a higher number of CD1a+ Langerhans cells than unaffected follicles. This finding suggests, as others have hypothesized, that the antigen-presenting Langerhans cells draw lymphocytes to the follicle, according to the investigators. Elevated numbers of Langerhans cells have also been reported in other forms of scarring alopecia, such as lichen planopilaris (LPP).

In the case of CCCA, CD1a+ Langerhans cells appear to localize to the hair follicle in response to stimulus such as an injury. The CD4+ cells that follow the Langerhans cells participate in an inflammatory reaction that drives follicle destruction. In addition to this damage and scarring, the inflammatory response is also likely to be disrupting the blood supply.

“Fibroplasia associated with follicular scarring displaces blood vessels away from the outer root sheath epithelium,” the authors explained. Ultimately, “the mucinous fibroplasia and perifollicular fibrosis may disrupt and fragment blood vessels in the fibrous sheath, leaving only small clusters of vessels more distant to the keratinocytes in the outer root sheath.”

Prior studies of scarring alopecia diseases, including LLP, frontal fibrosing alopecia (FFA), and keratosis follicularis spinulosa decalvans (KFSD), have typically described a predominantly CD8+ lymphocytic infiltrate. The evidence from this study that the infiltrate is CD4+ predominant in CCCA supports the conclusion that the pathophysiologic features of this type of alopecia are unique, according to the authors.

Work by others has associated CCCA with mutations in the PAD13 gene, which suggests a defect in the formation of hair shaft structure, but this may speak to susceptibility but not the mechanism of hair follicle damage. Rather, this study suggests that it is the concentration of a CD4+ predominant lymphocytic infiltrate in the perifollicular space that induces the pathological events.

For determining the fundamental cause of CCCA, “it will be important to determine what recruits the Langerhans cells to affected follicles,” the investigators suggested. Meanwhile, they expressed hope that the progress being made into decoding the pathogenesis of CCCA will lead to novel therapeutic strategies.

The authors did not list any disclosures. The funding source was listed as the Center for Scientific Review (Grant/Award).

SOURCE: Flamm A et al. J Cutan Pathol. 2020 Feb 18.doi: 10.1111/cup.13666.

NATIONAL HARBOR, MD. – In a head-to-head comparison, the ultrathin-strut Orsiro drug-eluting stent (DES) is demonstrating a growing advantage over the thin-strut Xience DES stent in stable patients undergoing coronary revascularization, according to a presentation at the 2020 CRT meeting.

Ted Bostworth/MDedge News

“These results direct our attention to strut thickness and polymer composition as key attributes for stent design,” reported David E. Kandzari, MD, director of interventional cardiology at the Piedmont Heart Institute in Atlanta.

In the multinational BIOFLOW V trial, 1,334 patients were randomized in a two-to-one ratio to the Orsiro stent, which is composed of a bioabsorbable, sirolimus-eluting polymer, or to the Xience stent, which is composed of an everolimus-eluting durable polymer. Relative to the Xience device, which has thin struts of 81 microns in width, the struts of the Orsiro device, at 60 microns in width, are characterized as ultrathin.

In earlier published follow-up studies, the ultrathin device demonstrated a lower rate of target lesion (TL) failure at 1 year (5.9% vs. 9.2%; P = .032) and at 2 years (7.1% vs. 11.1%; P = .015), but the 3-year data are notable because they indicate that the relative advantage is continuing to grow, according to Dr. Kandzari.

At 3 years, with follow-up available for 94.8% and 94.2% of the Orsiro and Xience groups, respectively, the absolute relative difference in the primary endpoint of TL failure reached 5.4% (8.2% vs. 13.6%; P = .002) in favor of the Orsiro device.

For the components of the composite TL failure endpoint, which includes cardiovascular death, TL-related myocardial infarction, and TL revascularization, there were large relative advantages for every outcome except cardiovascular death, which did not differ between the Orsiro and Xience groups (1.1% vs. 1.2%, respectively; P = .1). Conversely, the TL-related MI (5.5% vs. 10.1%; P = .004) and ischemia-driven TL revascularization (3.4% vs. 6.9%; P = .008) rates were nearly cut in half in the Orsiro arm.

“The benefit appears to be bimodal in that there is a significant advantage in the periprocedural period [for the Orsiro device] and then a late advantage,” Dr. Kandzari reported.

Most TL-related MI in both groups, for example, occurred within the first 30 days of follow-up. Although there was a relative advantage for the Orsiro device in this early period (4.1% vs. 6.7%; P = .04), Dr. Kandzari indicated that the advantage between 30 days and 3 years was even more impressive (0.95% vs. 2.8%; P = .012).

Dr. Kandzari, showing a graph in which the line representing Orsiro device hugged the x axis as the line for the Xience device climbed, emphasized that the rate of target vessel MI at the end of follow-up was nearly three times greater for those randomized to the Xience device.

The patterns of ischemia-driven TL revascularization also diverged. In this case, the rates over the first 360 days were very similar for the two devices initially. At 1 year, the lower rate in the Orsiro device was not significantly different (2.0% vs. 2.3%; P = .72), but the lines began to separate at about 18 months. By the end of 3 years, the rate of ischemia-related TL revascularization was nearly 70% lower in the Orsiro arm (1.5% vs. 4.7%; P < .001).

The Orsiro device was also linked with a lower rate of definite or probable stent thrombosis when the two devices were compared from 30 days post implantation to 3 years of follow-up (0.1% vs. 1.2%; P = .018).

Noting that there are several features of the Orsiro device that might explain these results, including the width of the struts, the biodegradable polymer, and the type of anti-inflammatory coating, Dr. Kandzari said that it is difficult to determine which attributes account for the overall or the specific advantages observed for the Orsiro device in the BIOFLOW V trial.

However, he hypothesized that “there might be different time lines for different benefits” related to individual device characteristics. For example, the ultrathin struts might be important for the early relative advantages while the biodegradation of the strut might explain the reduced need for revascularization.

Overall, “there is an emerging evidence base consistent across clinical trials demonstrating a potential efficacy and safety difference in favor of ultrathin struts,” according to Dr. Kandzari.

The data are “remarkable,” according to James B. Hermiller, MD, an interventional cardiologist at the Heart Center of Indiana in Indianapolis. A panel member for the CRT late-breaking trial session where these data were presented, Dr. Hermiller was impressed by the very low rate of revascularization in the extended follow-up.

“We have all wanted to see a flattening of these event curves after a year,” Dr. Hermiller said. He indicated that the BIOFLOW V data represent a departure from the need for revascularization and other late events so commonly seen over lengthening follow-up with earlier generation devices.

SOURCE: Kandzari DE. CRT 2020, Late Breaking Trials session S300.

NATIONAL HARBOR, MD. – In a head-to-head comparison, the ultrathin-strut Orsiro drug-eluting stent (DES) is demonstrating a growing advantage over the thin-strut Xience DES stent in stable patients undergoing coronary revascularization, according to a presentation at the 2020 CRT meeting.

Ted Bostworth/MDedge News

“These results direct our attention to strut thickness and polymer composition as key attributes for stent design,” reported David E. Kandzari, MD, director of interventional cardiology at the Piedmont Heart Institute in Atlanta.

In the multinational BIOFLOW V trial, 1,334 patients were randomized in a two-to-one ratio to the Orsiro stent, which is composed of a bioabsorbable, sirolimus-eluting polymer, or to the Xience stent, which is composed of an everolimus-eluting durable polymer. Relative to the Xience device, which has thin struts of 81 microns in width, the struts of the Orsiro device, at 60 microns in width, are characterized as ultrathin.

In earlier published follow-up studies, the ultrathin device demonstrated a lower rate of target lesion (TL) failure at 1 year (5.9% vs. 9.2%; P = .032) and at 2 years (7.1% vs. 11.1%; P = .015), but the 3-year data are notable because they indicate that the relative advantage is continuing to grow, according to Dr. Kandzari.

At 3 years, with follow-up available for 94.8% and 94.2% of the Orsiro and Xience groups, respectively, the absolute relative difference in the primary endpoint of TL failure reached 5.4% (8.2% vs. 13.6%; P = .002) in favor of the Orsiro device.

For the components of the composite TL failure endpoint, which includes cardiovascular death, TL-related myocardial infarction, and TL revascularization, there were large relative advantages for every outcome except cardiovascular death, which did not differ between the Orsiro and Xience groups (1.1% vs. 1.2%, respectively; P = .1). Conversely, the TL-related MI (5.5% vs. 10.1%; P = .004) and ischemia-driven TL revascularization (3.4% vs. 6.9%; P = .008) rates were nearly cut in half in the Orsiro arm.

“The benefit appears to be bimodal in that there is a significant advantage in the periprocedural period [for the Orsiro device] and then a late advantage,” Dr. Kandzari reported.

Most TL-related MI in both groups, for example, occurred within the first 30 days of follow-up. Although there was a relative advantage for the Orsiro device in this early period (4.1% vs. 6.7%; P = .04), Dr. Kandzari indicated that the advantage between 30 days and 3 years was even more impressive (0.95% vs. 2.8%; P = .012).

Dr. Kandzari, showing a graph in which the line representing Orsiro device hugged the x axis as the line for the Xience device climbed, emphasized that the rate of target vessel MI at the end of follow-up was nearly three times greater for those randomized to the Xience device.

The patterns of ischemia-driven TL revascularization also diverged. In this case, the rates over the first 360 days were very similar for the two devices initially. At 1 year, the lower rate in the Orsiro device was not significantly different (2.0% vs. 2.3%; P = .72), but the lines began to separate at about 18 months. By the end of 3 years, the rate of ischemia-related TL revascularization was nearly 70% lower in the Orsiro arm (1.5% vs. 4.7%; P < .001).

The Orsiro device was also linked with a lower rate of definite or probable stent thrombosis when the two devices were compared from 30 days post implantation to 3 years of follow-up (0.1% vs. 1.2%; P = .018).

Noting that there are several features of the Orsiro device that might explain these results, including the width of the struts, the biodegradable polymer, and the type of anti-inflammatory coating, Dr. Kandzari said that it is difficult to determine which attributes account for the overall or the specific advantages observed for the Orsiro device in the BIOFLOW V trial.

However, he hypothesized that “there might be different time lines for different benefits” related to individual device characteristics. For example, the ultrathin struts might be important for the early relative advantages while the biodegradation of the strut might explain the reduced need for revascularization.

Overall, “there is an emerging evidence base consistent across clinical trials demonstrating a potential efficacy and safety difference in favor of ultrathin struts,” according to Dr. Kandzari.

The data are “remarkable,” according to James B. Hermiller, MD, an interventional cardiologist at the Heart Center of Indiana in Indianapolis. A panel member for the CRT late-breaking trial session where these data were presented, Dr. Hermiller was impressed by the very low rate of revascularization in the extended follow-up.

“We have all wanted to see a flattening of these event curves after a year,” Dr. Hermiller said. He indicated that the BIOFLOW V data represent a departure from the need for revascularization and other late events so commonly seen over lengthening follow-up with earlier generation devices.

SOURCE: Kandzari DE. CRT 2020, Late Breaking Trials session S300.

NATIONAL HARBOR, MD. – In a head-to-head comparison, the ultrathin-strut Orsiro drug-eluting stent (DES) is demonstrating a growing advantage over the thin-strut Xience DES stent in stable patients undergoing coronary revascularization, according to a presentation at the 2020 CRT meeting.

Ted Bostworth/MDedge News

“These results direct our attention to strut thickness and polymer composition as key attributes for stent design,” reported David E. Kandzari, MD, director of interventional cardiology at the Piedmont Heart Institute in Atlanta.

In the multinational BIOFLOW V trial, 1,334 patients were randomized in a two-to-one ratio to the Orsiro stent, which is composed of a bioabsorbable, sirolimus-eluting polymer, or to the Xience stent, which is composed of an everolimus-eluting durable polymer. Relative to the Xience device, which has thin struts of 81 microns in width, the struts of the Orsiro device, at 60 microns in width, are characterized as ultrathin.

In earlier published follow-up studies, the ultrathin device demonstrated a lower rate of target lesion (TL) failure at 1 year (5.9% vs. 9.2%; P = .032) and at 2 years (7.1% vs. 11.1%; P = .015), but the 3-year data are notable because they indicate that the relative advantage is continuing to grow, according to Dr. Kandzari.

At 3 years, with follow-up available for 94.8% and 94.2% of the Orsiro and Xience groups, respectively, the absolute relative difference in the primary endpoint of TL failure reached 5.4% (8.2% vs. 13.6%; P = .002) in favor of the Orsiro device.

For the components of the composite TL failure endpoint, which includes cardiovascular death, TL-related myocardial infarction, and TL revascularization, there were large relative advantages for every outcome except cardiovascular death, which did not differ between the Orsiro and Xience groups (1.1% vs. 1.2%, respectively; P = .1). Conversely, the TL-related MI (5.5% vs. 10.1%; P = .004) and ischemia-driven TL revascularization (3.4% vs. 6.9%; P = .008) rates were nearly cut in half in the Orsiro arm.

“The benefit appears to be bimodal in that there is a significant advantage in the periprocedural period [for the Orsiro device] and then a late advantage,” Dr. Kandzari reported.

Most TL-related MI in both groups, for example, occurred within the first 30 days of follow-up. Although there was a relative advantage for the Orsiro device in this early period (4.1% vs. 6.7%; P = .04), Dr. Kandzari indicated that the advantage between 30 days and 3 years was even more impressive (0.95% vs. 2.8%; P = .012).

Dr. Kandzari, showing a graph in which the line representing Orsiro device hugged the x axis as the line for the Xience device climbed, emphasized that the rate of target vessel MI at the end of follow-up was nearly three times greater for those randomized to the Xience device.

The patterns of ischemia-driven TL revascularization also diverged. In this case, the rates over the first 360 days were very similar for the two devices initially. At 1 year, the lower rate in the Orsiro device was not significantly different (2.0% vs. 2.3%; P = .72), but the lines began to separate at about 18 months. By the end of 3 years, the rate of ischemia-related TL revascularization was nearly 70% lower in the Orsiro arm (1.5% vs. 4.7%; P < .001).

The Orsiro device was also linked with a lower rate of definite or probable stent thrombosis when the two devices were compared from 30 days post implantation to 3 years of follow-up (0.1% vs. 1.2%; P = .018).

Noting that there are several features of the Orsiro device that might explain these results, including the width of the struts, the biodegradable polymer, and the type of anti-inflammatory coating, Dr. Kandzari said that it is difficult to determine which attributes account for the overall or the specific advantages observed for the Orsiro device in the BIOFLOW V trial.

However, he hypothesized that “there might be different time lines for different benefits” related to individual device characteristics. For example, the ultrathin struts might be important for the early relative advantages while the biodegradation of the strut might explain the reduced need for revascularization.

Overall, “there is an emerging evidence base consistent across clinical trials demonstrating a potential efficacy and safety difference in favor of ultrathin struts,” according to Dr. Kandzari.

The data are “remarkable,” according to James B. Hermiller, MD, an interventional cardiologist at the Heart Center of Indiana in Indianapolis. A panel member for the CRT late-breaking trial session where these data were presented, Dr. Hermiller was impressed by the very low rate of revascularization in the extended follow-up.

“We have all wanted to see a flattening of these event curves after a year,” Dr. Hermiller said. He indicated that the BIOFLOW V data represent a departure from the need for revascularization and other late events so commonly seen over lengthening follow-up with earlier generation devices.

SOURCE: Kandzari DE. CRT 2020, Late Breaking Trials session S300.

NATIONAL HARBOR, MD. – In a pooled analysis of three trials conducted with the transcatheter Carillon Mitral Contour System for mitral valve repair, the 5-year survival is 56.2%, which is an encouraging outcome that justifies the ongoing multinational pivotal Carillon trial, according to the principal investigator of the analysis presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

In patients with functional mitral valve regurgitation (FMR), “the Carillon device shows extremely encouraging long-term mortality data from prospective controlled trials in comparison with guideline-directed medical therapy or with the COAPT results,” according to Janusz Lipiecki, MD, PhD, department of cardiology, University Hospital, Clermont-Ferrand, France.

The COAPT trial is an important benchmark, because it was the first large, randomized trial to show benefit for a percutaneous device in the treatment of heart failure patients with moderate to severe FMR (N Engl J Med. 2018;379:2307-18). The study associated the MitraClip with a nearly 40% reduction in all-cause mortality (29.1% vs. 46.1%) at 24 months, relative to guideline-directed medical therapy (GDMT).

The Carillon device, which is also delivered percutaneously, does not engage the valve leaflets to treat FMR. Rather, it is anchored in coronary sinus to reform the mitral annulus. This reduces FMR without damage to the mitral valve, thus preserving the potential for future valve repairs, according to Dr. Lipiecki, who reported that more than 1,100 devices have now been implanted, mostly in Europe.

The data so far are encouraging, said Dr. Lipiecki, who provided survival data in 74 patients followed for at least 5 years. Of these, 23 were drawn from the REDUCE FMR trial, which was blinded and sham controlled, and the remainder from the TITAN and TITAN II studies, which were prospective but not controlled.

In this series of 74 patients, there were no serious complications associated with the procedure, and all achieved a reduction in mitral regurgitation at 12 months, Dr. Lipiecki said. Furthermore, the reduction in FMR was associated with improvements in symptoms and “favorable remodeling” reflected in reduced left ventricular volume, he said.

In this series, the 5-year survival is 56%, which substantially exceeds what would be expected with GDMT, according to Dr. Lipiecki.

There were no baseline predictors of long-term survival, but improvements within the 6 months in functional heart class, 6-minute walk distance (6MWD), and mitral regurgitation were significantly associated with a greater likelihood of being alive at 5 years.

Although there is no comparable follow-up with other devices, including the MitraClip, Dr. Lipiecki did compare the 67.9% survival at 3 years in this series to that of the COAPT trial. He restricted the comparison to those treated for grade 3+ or 4+ mitral regurgitation. At 36 months, survival rates were 57.2% and 44.5% for those treated with MitraClip and GDMT, respectively.

“COAPT patients might not be comparable for a variety of reasons, including the anatomic restrictions important to the use of either of these devices,” Dr. Lipiecki acknowledged, but he said the long-term data with the Carillon device provide support for the pivotal Carillon trial now enrolling.

In this blinded trial, more than 350 patients at 75 sites are being randomized to placement of the Carillon device, which has been available in Europe since 2011, or a sham procedure. The trial is scheduled for completion in 2025.

NATIONAL HARBOR, MD. – In a pooled analysis of three trials conducted with the transcatheter Carillon Mitral Contour System for mitral valve repair, the 5-year survival is 56.2%, which is an encouraging outcome that justifies the ongoing multinational pivotal Carillon trial, according to the principal investigator of the analysis presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

In patients with functional mitral valve regurgitation (FMR), “the Carillon device shows extremely encouraging long-term mortality data from prospective controlled trials in comparison with guideline-directed medical therapy or with the COAPT results,” according to Janusz Lipiecki, MD, PhD, department of cardiology, University Hospital, Clermont-Ferrand, France.

The COAPT trial is an important benchmark, because it was the first large, randomized trial to show benefit for a percutaneous device in the treatment of heart failure patients with moderate to severe FMR (N Engl J Med. 2018;379:2307-18). The study associated the MitraClip with a nearly 40% reduction in all-cause mortality (29.1% vs. 46.1%) at 24 months, relative to guideline-directed medical therapy (GDMT).

The Carillon device, which is also delivered percutaneously, does not engage the valve leaflets to treat FMR. Rather, it is anchored in coronary sinus to reform the mitral annulus. This reduces FMR without damage to the mitral valve, thus preserving the potential for future valve repairs, according to Dr. Lipiecki, who reported that more than 1,100 devices have now been implanted, mostly in Europe.

The data so far are encouraging, said Dr. Lipiecki, who provided survival data in 74 patients followed for at least 5 years. Of these, 23 were drawn from the REDUCE FMR trial, which was blinded and sham controlled, and the remainder from the TITAN and TITAN II studies, which were prospective but not controlled.

In this series of 74 patients, there were no serious complications associated with the procedure, and all achieved a reduction in mitral regurgitation at 12 months, Dr. Lipiecki said. Furthermore, the reduction in FMR was associated with improvements in symptoms and “favorable remodeling” reflected in reduced left ventricular volume, he said.

In this series, the 5-year survival is 56%, which substantially exceeds what would be expected with GDMT, according to Dr. Lipiecki.

There were no baseline predictors of long-term survival, but improvements within the 6 months in functional heart class, 6-minute walk distance (6MWD), and mitral regurgitation were significantly associated with a greater likelihood of being alive at 5 years.

Although there is no comparable follow-up with other devices, including the MitraClip, Dr. Lipiecki did compare the 67.9% survival at 3 years in this series to that of the COAPT trial. He restricted the comparison to those treated for grade 3+ or 4+ mitral regurgitation. At 36 months, survival rates were 57.2% and 44.5% for those treated with MitraClip and GDMT, respectively.

“COAPT patients might not be comparable for a variety of reasons, including the anatomic restrictions important to the use of either of these devices,” Dr. Lipiecki acknowledged, but he said the long-term data with the Carillon device provide support for the pivotal Carillon trial now enrolling.

In this blinded trial, more than 350 patients at 75 sites are being randomized to placement of the Carillon device, which has been available in Europe since 2011, or a sham procedure. The trial is scheduled for completion in 2025.

NATIONAL HARBOR, MD. – In a pooled analysis of three trials conducted with the transcatheter Carillon Mitral Contour System for mitral valve repair, the 5-year survival is 56.2%, which is an encouraging outcome that justifies the ongoing multinational pivotal Carillon trial, according to the principal investigator of the analysis presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

In patients with functional mitral valve regurgitation (FMR), “the Carillon device shows extremely encouraging long-term mortality data from prospective controlled trials in comparison with guideline-directed medical therapy or with the COAPT results,” according to Janusz Lipiecki, MD, PhD, department of cardiology, University Hospital, Clermont-Ferrand, France.

The COAPT trial is an important benchmark, because it was the first large, randomized trial to show benefit for a percutaneous device in the treatment of heart failure patients with moderate to severe FMR (N Engl J Med. 2018;379:2307-18). The study associated the MitraClip with a nearly 40% reduction in all-cause mortality (29.1% vs. 46.1%) at 24 months, relative to guideline-directed medical therapy (GDMT).

The Carillon device, which is also delivered percutaneously, does not engage the valve leaflets to treat FMR. Rather, it is anchored in coronary sinus to reform the mitral annulus. This reduces FMR without damage to the mitral valve, thus preserving the potential for future valve repairs, according to Dr. Lipiecki, who reported that more than 1,100 devices have now been implanted, mostly in Europe.

The data so far are encouraging, said Dr. Lipiecki, who provided survival data in 74 patients followed for at least 5 years. Of these, 23 were drawn from the REDUCE FMR trial, which was blinded and sham controlled, and the remainder from the TITAN and TITAN II studies, which were prospective but not controlled.

In this series of 74 patients, there were no serious complications associated with the procedure, and all achieved a reduction in mitral regurgitation at 12 months, Dr. Lipiecki said. Furthermore, the reduction in FMR was associated with improvements in symptoms and “favorable remodeling” reflected in reduced left ventricular volume, he said.

In this series, the 5-year survival is 56%, which substantially exceeds what would be expected with GDMT, according to Dr. Lipiecki.

There were no baseline predictors of long-term survival, but improvements within the 6 months in functional heart class, 6-minute walk distance (6MWD), and mitral regurgitation were significantly associated with a greater likelihood of being alive at 5 years.

Although there is no comparable follow-up with other devices, including the MitraClip, Dr. Lipiecki did compare the 67.9% survival at 3 years in this series to that of the COAPT trial. He restricted the comparison to those treated for grade 3+ or 4+ mitral regurgitation. At 36 months, survival rates were 57.2% and 44.5% for those treated with MitraClip and GDMT, respectively.

“COAPT patients might not be comparable for a variety of reasons, including the anatomic restrictions important to the use of either of these devices,” Dr. Lipiecki acknowledged, but he said the long-term data with the Carillon device provide support for the pivotal Carillon trial now enrolling.

In this blinded trial, more than 350 patients at 75 sites are being randomized to placement of the Carillon device, which has been available in Europe since 2011, or a sham procedure. The trial is scheduled for completion in 2025.

NATIONAL HARBOR, MD. – Anticoagulation reduces the risk of leaflet thrombosis at 30 days relative to antiplatelet therapy in low-risk patients undergoing transcatheter aortic valve replacement (TAVR), according to a randomized feasibility study presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute..

Ted Bosworth/MDedge News

At 30 days, oral anticoagulation with warfarin did not appear to be associated with any increased risk of adverse outcomes, including bleeding events, relative to aspirin, according to Toby Rogers, MD, PhD, the scientific lead for the Structural Heart Disease Program at MedStar Heart & Vascular Institute, Washington.

The rationale for this feasibility study, called LRT 2.0, was to evaluate whether anticoagulation after low-risk TAVR reduces the risk of early subclinical leaflet thrombosis, a potential threat to long-term valve survival.

“In the first LRT trial, HALT [hypoattenuated leaflet thickening] was observed in 13.5% of patients on antiplatelet therapy but only 4.8% of those on oral anticoagulation,” Dr. Rogers said.

The two strategies have not been adequately compared, particularly in low-risk patients, according to Dr. Rogers. He noted that current guidelines recommend dual-antiplatelet therapy after TAVR but the oral anticoagulant warfarin after surgical valve replacement, a situation he characterized as a “discrepancy.”

In the multicenter, randomized LRT 2.0 trial, 94 patients undergoing TAVR and meeting prespecified low-risk criteria, such as a Society of Thoracic Surgeons score of 3 or lower, were randomized to warfarin or to aspirin. The study called for an enrollment of 200 patients but was closed early when the Food and Drug Administration approved TAVR for low-risk patients in 2019, causing “enrollment to dry up over night.”

However, an additional registry cohort was included in a separate analysis. This registry cohort consisted of 30 patients who were evaluated for trial inclusion but were found to be inappropriate for randomization because they already had an indication for anticoagulation or had an elevated risk of bleeding. These low-risk TAVR patients were assigned to anticoagulation or antiplatelet therapy as appropriate.

When the randomized groups were compared, the incidence of HALT at 30 days on CT scan was 4.7% among those on warfarin and 16.3% (P = .07) among those taking aspirin. Dr. Rogers believes the near miss for statistical significance was a problem of power, a position supported by the pooled analysis of randomized and registry patients. With the added patients, the difference in HALT did reach significance (3.1% vs. 16.4%; P = .01).

The numerical differences in reduced leaflet motion and hypoattenuated motion favoring anticoagulation trended for significance in the randomized cohort (P = .12) but reached the cusp of significance in the pooled cohort (1.5% vs. 9.4%; P = .052) for both reduced leaflet motion and hypoattenuated motion).

There were no deaths recorded in any treatment arm, whether restricted to the randomized trial or within the pooled cohort. For the pooled cohort, there were more strokes in the aspirin arm (5.4% vs. 1.5%) but Dr. Rogers said that no conclusions could be drawn about relative risk because of the study size and small number of events.

For anticoagulation relative to antiplatelet therapy, respectively, the incidence of new-onset atrial fibrillation (1.5% vs. 1.8%), pacemaker implantation (11.8% vs. 7.1%), major bleeding (1.5% vs. 5.4%), and median length of stay (2.2 vs. 2.4 days) were all similar. The improvements in hemodynamics 30 days after TAVR were substantial and similar in the two groups, according to Dr. Rogers.

Emphasizing that this is a feasibility study, Dr. Rogers cautioned that these data do not necessarily demonstrate that anticoagulation is a better strategy than antiplatelet therapy in low-risk patients after TAVR, but they do associate anticoagulation with a reduced risk of early leaflet thrombosis.

“We fear leaflet thrombosis for the potential that it will negatively impact valve durability, which is particularly important in younger lower-risk patients who might outlive their first valve prosthesis,” Dr. Rogers said.

Panelists at the late-breaking clinical trial session expressed interest in this concept but generally agreed that longer follow-up is needed. This additional follow-up is important for monitoring effect on leaflet thrombosis as well as on the overall impact of these strategies on adverse events.

“We need to see CT scans at later time points because we do not know where this complication comes from. The trigger for leaflet thrombosis might still be there after 30 days,” said Andreas Baumbach, MD, professor of interventional cardiology at the University of Bristol (England). However, he agreed that this is an important line of research, because the potential risk of leaflet thrombosis is “a very important question for us.”

Dr. Rogers reported financial relationships with Edwards Lifesciences and Medtronic.

NATIONAL HARBOR, MD. – Anticoagulation reduces the risk of leaflet thrombosis at 30 days relative to antiplatelet therapy in low-risk patients undergoing transcatheter aortic valve replacement (TAVR), according to a randomized feasibility study presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute..

Ted Bosworth/MDedge News

At 30 days, oral anticoagulation with warfarin did not appear to be associated with any increased risk of adverse outcomes, including bleeding events, relative to aspirin, according to Toby Rogers, MD, PhD, the scientific lead for the Structural Heart Disease Program at MedStar Heart & Vascular Institute, Washington.

The rationale for this feasibility study, called LRT 2.0, was to evaluate whether anticoagulation after low-risk TAVR reduces the risk of early subclinical leaflet thrombosis, a potential threat to long-term valve survival.

“In the first LRT trial, HALT [hypoattenuated leaflet thickening] was observed in 13.5% of patients on antiplatelet therapy but only 4.8% of those on oral anticoagulation,” Dr. Rogers said.

The two strategies have not been adequately compared, particularly in low-risk patients, according to Dr. Rogers. He noted that current guidelines recommend dual-antiplatelet therapy after TAVR but the oral anticoagulant warfarin after surgical valve replacement, a situation he characterized as a “discrepancy.”

In the multicenter, randomized LRT 2.0 trial, 94 patients undergoing TAVR and meeting prespecified low-risk criteria, such as a Society of Thoracic Surgeons score of 3 or lower, were randomized to warfarin or to aspirin. The study called for an enrollment of 200 patients but was closed early when the Food and Drug Administration approved TAVR for low-risk patients in 2019, causing “enrollment to dry up over night.”

However, an additional registry cohort was included in a separate analysis. This registry cohort consisted of 30 patients who were evaluated for trial inclusion but were found to be inappropriate for randomization because they already had an indication for anticoagulation or had an elevated risk of bleeding. These low-risk TAVR patients were assigned to anticoagulation or antiplatelet therapy as appropriate.

When the randomized groups were compared, the incidence of HALT at 30 days on CT scan was 4.7% among those on warfarin and 16.3% (P = .07) among those taking aspirin. Dr. Rogers believes the near miss for statistical significance was a problem of power, a position supported by the pooled analysis of randomized and registry patients. With the added patients, the difference in HALT did reach significance (3.1% vs. 16.4%; P = .01).

The numerical differences in reduced leaflet motion and hypoattenuated motion favoring anticoagulation trended for significance in the randomized cohort (P = .12) but reached the cusp of significance in the pooled cohort (1.5% vs. 9.4%; P = .052) for both reduced leaflet motion and hypoattenuated motion).

There were no deaths recorded in any treatment arm, whether restricted to the randomized trial or within the pooled cohort. For the pooled cohort, there were more strokes in the aspirin arm (5.4% vs. 1.5%) but Dr. Rogers said that no conclusions could be drawn about relative risk because of the study size and small number of events.

For anticoagulation relative to antiplatelet therapy, respectively, the incidence of new-onset atrial fibrillation (1.5% vs. 1.8%), pacemaker implantation (11.8% vs. 7.1%), major bleeding (1.5% vs. 5.4%), and median length of stay (2.2 vs. 2.4 days) were all similar. The improvements in hemodynamics 30 days after TAVR were substantial and similar in the two groups, according to Dr. Rogers.

Emphasizing that this is a feasibility study, Dr. Rogers cautioned that these data do not necessarily demonstrate that anticoagulation is a better strategy than antiplatelet therapy in low-risk patients after TAVR, but they do associate anticoagulation with a reduced risk of early leaflet thrombosis.

“We fear leaflet thrombosis for the potential that it will negatively impact valve durability, which is particularly important in younger lower-risk patients who might outlive their first valve prosthesis,” Dr. Rogers said.

Panelists at the late-breaking clinical trial session expressed interest in this concept but generally agreed that longer follow-up is needed. This additional follow-up is important for monitoring effect on leaflet thrombosis as well as on the overall impact of these strategies on adverse events.

“We need to see CT scans at later time points because we do not know where this complication comes from. The trigger for leaflet thrombosis might still be there after 30 days,” said Andreas Baumbach, MD, professor of interventional cardiology at the University of Bristol (England). However, he agreed that this is an important line of research, because the potential risk of leaflet thrombosis is “a very important question for us.”

Dr. Rogers reported financial relationships with Edwards Lifesciences and Medtronic.

NATIONAL HARBOR, MD. – Anticoagulation reduces the risk of leaflet thrombosis at 30 days relative to antiplatelet therapy in low-risk patients undergoing transcatheter aortic valve replacement (TAVR), according to a randomized feasibility study presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute..

Ted Bosworth/MDedge News

At 30 days, oral anticoagulation with warfarin did not appear to be associated with any increased risk of adverse outcomes, including bleeding events, relative to aspirin, according to Toby Rogers, MD, PhD, the scientific lead for the Structural Heart Disease Program at MedStar Heart & Vascular Institute, Washington.

The rationale for this feasibility study, called LRT 2.0, was to evaluate whether anticoagulation after low-risk TAVR reduces the risk of early subclinical leaflet thrombosis, a potential threat to long-term valve survival.

“In the first LRT trial, HALT [hypoattenuated leaflet thickening] was observed in 13.5% of patients on antiplatelet therapy but only 4.8% of those on oral anticoagulation,” Dr. Rogers said.

The two strategies have not been adequately compared, particularly in low-risk patients, according to Dr. Rogers. He noted that current guidelines recommend dual-antiplatelet therapy after TAVR but the oral anticoagulant warfarin after surgical valve replacement, a situation he characterized as a “discrepancy.”

In the multicenter, randomized LRT 2.0 trial, 94 patients undergoing TAVR and meeting prespecified low-risk criteria, such as a Society of Thoracic Surgeons score of 3 or lower, were randomized to warfarin or to aspirin. The study called for an enrollment of 200 patients but was closed early when the Food and Drug Administration approved TAVR for low-risk patients in 2019, causing “enrollment to dry up over night.”

However, an additional registry cohort was included in a separate analysis. This registry cohort consisted of 30 patients who were evaluated for trial inclusion but were found to be inappropriate for randomization because they already had an indication for anticoagulation or had an elevated risk of bleeding. These low-risk TAVR patients were assigned to anticoagulation or antiplatelet therapy as appropriate.

When the randomized groups were compared, the incidence of HALT at 30 days on CT scan was 4.7% among those on warfarin and 16.3% (P = .07) among those taking aspirin. Dr. Rogers believes the near miss for statistical significance was a problem of power, a position supported by the pooled analysis of randomized and registry patients. With the added patients, the difference in HALT did reach significance (3.1% vs. 16.4%; P = .01).

The numerical differences in reduced leaflet motion and hypoattenuated motion favoring anticoagulation trended for significance in the randomized cohort (P = .12) but reached the cusp of significance in the pooled cohort (1.5% vs. 9.4%; P = .052) for both reduced leaflet motion and hypoattenuated motion).

There were no deaths recorded in any treatment arm, whether restricted to the randomized trial or within the pooled cohort. For the pooled cohort, there were more strokes in the aspirin arm (5.4% vs. 1.5%) but Dr. Rogers said that no conclusions could be drawn about relative risk because of the study size and small number of events.

For anticoagulation relative to antiplatelet therapy, respectively, the incidence of new-onset atrial fibrillation (1.5% vs. 1.8%), pacemaker implantation (11.8% vs. 7.1%), major bleeding (1.5% vs. 5.4%), and median length of stay (2.2 vs. 2.4 days) were all similar. The improvements in hemodynamics 30 days after TAVR were substantial and similar in the two groups, according to Dr. Rogers.

Emphasizing that this is a feasibility study, Dr. Rogers cautioned that these data do not necessarily demonstrate that anticoagulation is a better strategy than antiplatelet therapy in low-risk patients after TAVR, but they do associate anticoagulation with a reduced risk of early leaflet thrombosis.

“We fear leaflet thrombosis for the potential that it will negatively impact valve durability, which is particularly important in younger lower-risk patients who might outlive their first valve prosthesis,” Dr. Rogers said.

Panelists at the late-breaking clinical trial session expressed interest in this concept but generally agreed that longer follow-up is needed. This additional follow-up is important for monitoring effect on leaflet thrombosis as well as on the overall impact of these strategies on adverse events.

“We need to see CT scans at later time points because we do not know where this complication comes from. The trigger for leaflet thrombosis might still be there after 30 days,” said Andreas Baumbach, MD, professor of interventional cardiology at the University of Bristol (England). However, he agreed that this is an important line of research, because the potential risk of leaflet thrombosis is “a very important question for us.”

Dr. Rogers reported financial relationships with Edwards Lifesciences and Medtronic.

NATIONAL HARBOR, MD. – Acute kidney injury (AKI), a potentially modifiable risk factor in some cases, predicts increased mortality within the first year after transcatheter aortic valve transplantation (TAVR), according to an analysis of a U.S. registry presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

“After adjustment, there are higher rates of all-cause mortality regardless of the severity of AKI,” reported Howard M. Julien, MD, of the University of Pennsylvania, Philadelphia.

Relative to the absence of AKI (stage 0), the hazard ratio for death at 1 year was more than threefold greater (HR, 3.26), even for those with stage 1 AKI. When unadjusted for covariates, it remained more than twice as high (HR, 2.67; P less than .001), Dr. Julien reported.

For stage 3 AKI, the unadjusted risk was more than nine times higher and remained roughly seven times greater after adjustment (HR, 7.04; P less than .001). Stage 2 AKI was linked with an adjusted risk of about the same magnitude.

Drawn from the National Cardiovascular TAVR Registry, which is maintained jointly by the Society of Thoracic Surgeons and the American College of Cardiology, data were analyzed on more than 100,000 TAVRs performed during 2012-2018. A subset of TAVRs performed between January 2016 and June 2018 served as a source of trends in what Dr. Julien described as the “modern era” of this procedure.

The incidence of AKI overall was about 10%, but rates were higher at the earliest time point in the analysis and fell modestly over the study period for all three stages. In a logistic regression analysis, the factors associated with the greatest odds ratio of developing AKI in patients following TAVR were conversion to open heart surgery (OR, 10.84, P less than .001), nonfemoral access (OR, 2.33; P less than .001), anemia (OR, 1.90; P less than .001), general versus moderate sedation (OR, 1.62; P less than .001), diabetes (OR, 1.61; P less than .001), and cardiogenic shock within 24 hours (OR, 1.60; P less than .023).

Other factors with a significant but lower relative risk association with AKI included a high contrast volume (OR, 1.004; P less than .001), use of a self-expanding valve (HR, 1.22; P = .009), severe lung disease (OR, 1.21; P = .043) and prior peripheral artery disease (HR, 1.20; P = .043).

“The message from these data is that there appears to be a cluster of patients who are unstable at the time of their procedure and are more likely to develop the most severe forms of AKI,” Dr. Julien reported.

The higher rate of AKI in patients who have diabetes is “not surprising,” but several of the factors associated with AKI are potentially modifiable. This includes choices in regard to sedation and arterial access. The value of modifying the amount of contrast is less clear, because the volume of contrast was no longer significant after an adjustment with multivariate analysis.

In fact, all of these factors require validation. Dr. Julien warned that neither the cause of AKI nor its temporal relationship to TAVR could be consistently determined from the registry data. In addition, retrospective analyses always include the potential for unrecognized residual confounders.

Still, these data are useful for drawing attention to the fact that AKI is a common complication of TAVR and one that is associated with adverse outcomes, including reduced survival at 1 year.

“The factors taken from these data might be useful to help identify patients who are at risk of the most severe forms of AKI and, hopefully, lead to prevention strategies that take these characteristics into consideration,” Dr. Julien said.

Dr. Julien reported no potential financial conflicts of interest.

NATIONAL HARBOR, MD. – Acute kidney injury (AKI), a potentially modifiable risk factor in some cases, predicts increased mortality within the first year after transcatheter aortic valve transplantation (TAVR), according to an analysis of a U.S. registry presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

“After adjustment, there are higher rates of all-cause mortality regardless of the severity of AKI,” reported Howard M. Julien, MD, of the University of Pennsylvania, Philadelphia.

Relative to the absence of AKI (stage 0), the hazard ratio for death at 1 year was more than threefold greater (HR, 3.26), even for those with stage 1 AKI. When unadjusted for covariates, it remained more than twice as high (HR, 2.67; P less than .001), Dr. Julien reported.

For stage 3 AKI, the unadjusted risk was more than nine times higher and remained roughly seven times greater after adjustment (HR, 7.04; P less than .001). Stage 2 AKI was linked with an adjusted risk of about the same magnitude.

Drawn from the National Cardiovascular TAVR Registry, which is maintained jointly by the Society of Thoracic Surgeons and the American College of Cardiology, data were analyzed on more than 100,000 TAVRs performed during 2012-2018. A subset of TAVRs performed between January 2016 and June 2018 served as a source of trends in what Dr. Julien described as the “modern era” of this procedure.

The incidence of AKI overall was about 10%, but rates were higher at the earliest time point in the analysis and fell modestly over the study period for all three stages. In a logistic regression analysis, the factors associated with the greatest odds ratio of developing AKI in patients following TAVR were conversion to open heart surgery (OR, 10.84, P less than .001), nonfemoral access (OR, 2.33; P less than .001), anemia (OR, 1.90; P less than .001), general versus moderate sedation (OR, 1.62; P less than .001), diabetes (OR, 1.61; P less than .001), and cardiogenic shock within 24 hours (OR, 1.60; P less than .023).

Other factors with a significant but lower relative risk association with AKI included a high contrast volume (OR, 1.004; P less than .001), use of a self-expanding valve (HR, 1.22; P = .009), severe lung disease (OR, 1.21; P = .043) and prior peripheral artery disease (HR, 1.20; P = .043).

“The message from these data is that there appears to be a cluster of patients who are unstable at the time of their procedure and are more likely to develop the most severe forms of AKI,” Dr. Julien reported.

The higher rate of AKI in patients who have diabetes is “not surprising,” but several of the factors associated with AKI are potentially modifiable. This includes choices in regard to sedation and arterial access. The value of modifying the amount of contrast is less clear, because the volume of contrast was no longer significant after an adjustment with multivariate analysis.

In fact, all of these factors require validation. Dr. Julien warned that neither the cause of AKI nor its temporal relationship to TAVR could be consistently determined from the registry data. In addition, retrospective analyses always include the potential for unrecognized residual confounders.

Still, these data are useful for drawing attention to the fact that AKI is a common complication of TAVR and one that is associated with adverse outcomes, including reduced survival at 1 year.

“The factors taken from these data might be useful to help identify patients who are at risk of the most severe forms of AKI and, hopefully, lead to prevention strategies that take these characteristics into consideration,” Dr. Julien said.

Dr. Julien reported no potential financial conflicts of interest.

NATIONAL HARBOR, MD. – Acute kidney injury (AKI), a potentially modifiable risk factor in some cases, predicts increased mortality within the first year after transcatheter aortic valve transplantation (TAVR), according to an analysis of a U.S. registry presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

“After adjustment, there are higher rates of all-cause mortality regardless of the severity of AKI,” reported Howard M. Julien, MD, of the University of Pennsylvania, Philadelphia.

Relative to the absence of AKI (stage 0), the hazard ratio for death at 1 year was more than threefold greater (HR, 3.26), even for those with stage 1 AKI. When unadjusted for covariates, it remained more than twice as high (HR, 2.67; P less than .001), Dr. Julien reported.

For stage 3 AKI, the unadjusted risk was more than nine times higher and remained roughly seven times greater after adjustment (HR, 7.04; P less than .001). Stage 2 AKI was linked with an adjusted risk of about the same magnitude.

Drawn from the National Cardiovascular TAVR Registry, which is maintained jointly by the Society of Thoracic Surgeons and the American College of Cardiology, data were analyzed on more than 100,000 TAVRs performed during 2012-2018. A subset of TAVRs performed between January 2016 and June 2018 served as a source of trends in what Dr. Julien described as the “modern era” of this procedure.

The incidence of AKI overall was about 10%, but rates were higher at the earliest time point in the analysis and fell modestly over the study period for all three stages. In a logistic regression analysis, the factors associated with the greatest odds ratio of developing AKI in patients following TAVR were conversion to open heart surgery (OR, 10.84, P less than .001), nonfemoral access (OR, 2.33; P less than .001), anemia (OR, 1.90; P less than .001), general versus moderate sedation (OR, 1.62; P less than .001), diabetes (OR, 1.61; P less than .001), and cardiogenic shock within 24 hours (OR, 1.60; P less than .023).

Other factors with a significant but lower relative risk association with AKI included a high contrast volume (OR, 1.004; P less than .001), use of a self-expanding valve (HR, 1.22; P = .009), severe lung disease (OR, 1.21; P = .043) and prior peripheral artery disease (HR, 1.20; P = .043).

“The message from these data is that there appears to be a cluster of patients who are unstable at the time of their procedure and are more likely to develop the most severe forms of AKI,” Dr. Julien reported.

The higher rate of AKI in patients who have diabetes is “not surprising,” but several of the factors associated with AKI are potentially modifiable. This includes choices in regard to sedation and arterial access. The value of modifying the amount of contrast is less clear, because the volume of contrast was no longer significant after an adjustment with multivariate analysis.

In fact, all of these factors require validation. Dr. Julien warned that neither the cause of AKI nor its temporal relationship to TAVR could be consistently determined from the registry data. In addition, retrospective analyses always include the potential for unrecognized residual confounders.

Still, these data are useful for drawing attention to the fact that AKI is a common complication of TAVR and one that is associated with adverse outcomes, including reduced survival at 1 year.

“The factors taken from these data might be useful to help identify patients who are at risk of the most severe forms of AKI and, hopefully, lead to prevention strategies that take these characteristics into consideration,” Dr. Julien said.

Dr. Julien reported no potential financial conflicts of interest.

NATIONAL HARBOR, MD. – Following a percutaneous intervention with a second-generation drug-eluting stent, a judicious interruption of antiplatelet therapy for noncardiac surgery does not increase risk of net adverse clinical events, according to a large dataset presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

Ted Bosworth/MDedge News

Drawn from a multicenter registry in South Korea, it is likely that those in whom antiplatelet therapy was stopped during the perioperative period were at a lower relative risk, but the data remain reassuring, according to Jung-Sun Kim, MD, PhD, professor of medicine at Yonsei University, Seoul, South Korea.

In the registry of patients with a second-generation drug-eluting stent (DES) undergoing noncardiac surgery, “antiplatelet therapy was discontinued in almost half of the patients,” Dr. Kim reported. When these patients were compared with those who did not discontinue antiplatelet therapy, the data, called an “exploratory analysis,” suggested “no increased risk” of a composite of major adverse cardiac events (MACE) or major bleeding.

The retrospective analysis involved 3,582 percutaneous intervention (PCI) patients who had received a second-generation DES and subsequently underwent noncardiac surgery. In 1,750 of these patients, antiplatelet therapy was temporarily discontinued. The remaining 1,832 remained on some form of antiplatelet treatment, whether aspirin, a P2Y12 inhibitor, or dual-antiplatelet therapy.

There were no significant differences in crude rates between groups in rates at 30 days of a composite endpoint of MACE, major bleeding as defined by the International Society on Thrombosis and Haemostasis, or net adverse clinical events (NACE), a composite of adverse events that included MACE and major bleeding.

Relative risks for antiplatelet discontinuation remained generally low even after multiple stratifications performed to explore different variables, including the types of antiplatelet therapy being taken at the time of discontinuation, the types of noncardiac surgery performed, and the duration of discontinuation.

Of these variables, the interval of discontinuation appeared to be most relevant. Antiplatelet discontinuation of 3 days or less appeared to be associated with a higher risk of bleeding, although the difference did not reach significance. Discontinuations of 9 days or more were associated with increased risk of MACE, and this difference did reach statistical significance (hazard ratio, 3.38; 95% confidence interval, 1.36-8.38).

“Discontinuation of antiplatelet therapy for a period of 4-8 days appears to be optimal,” Dr. Kim said.

In general, risk of MACE, major bleeding, or NACE could not be linked to type of surgery, with the exception of intra-abdominal surgery. For this procedure, there appeared to be a lower risk of MACE in those who discontinued relative to those who remained on antiplatelet therapy, Dr. Kim reported.

Importantly, because of the fact that the decision to stop antiplatelet treatment was made by treating physicians, the characteristics of those who discontinued or remained on antiplatelet therapy differed meaningfully. Specifically, those in the discontinuation group were younger and were less likely to have additional risks for thrombotic events such as diabetes or chronic kidney disease. In those who discontinued antiplatelets, the average time since PCI was 23 months versus 16 months in the continuation group.

In addition, “more of the patients underwent higher-risk surgeries in the discontinuation group,” Dr. Kim added.

Relative rates of MACE and NACE remained similar even after risk adjustment, but Dr. Kim advised that the data should be “interpreted cautiously” because of the retrospective nature of the analysis.

A panel of experts invited to comment on the presentation agreed. These data were considered reassuring for clinicians considering an interruption of antiplatelet therapy following PCI with a second-generation DES, but there was uncertainty about their value for defining which patients are the best candidates.

The decision to discontinue antiplatelet drugs for noncardiac surgery is an important and common dilemma, but these data might be best characterized as “a testament to Korean cardiologists making good decisions,” said David J. Moliterno, MD, chairman of the department of medicine at University of Kentucky Health Care, Lexington.

Dr. Kim reported no potential financial conflicts of interest.

NATIONAL HARBOR, MD. – Following a percutaneous intervention with a second-generation drug-eluting stent, a judicious interruption of antiplatelet therapy for noncardiac surgery does not increase risk of net adverse clinical events, according to a large dataset presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

Ted Bosworth/MDedge News

Drawn from a multicenter registry in South Korea, it is likely that those in whom antiplatelet therapy was stopped during the perioperative period were at a lower relative risk, but the data remain reassuring, according to Jung-Sun Kim, MD, PhD, professor of medicine at Yonsei University, Seoul, South Korea.

In the registry of patients with a second-generation drug-eluting stent (DES) undergoing noncardiac surgery, “antiplatelet therapy was discontinued in almost half of the patients,” Dr. Kim reported. When these patients were compared with those who did not discontinue antiplatelet therapy, the data, called an “exploratory analysis,” suggested “no increased risk” of a composite of major adverse cardiac events (MACE) or major bleeding.

The retrospective analysis involved 3,582 percutaneous intervention (PCI) patients who had received a second-generation DES and subsequently underwent noncardiac surgery. In 1,750 of these patients, antiplatelet therapy was temporarily discontinued. The remaining 1,832 remained on some form of antiplatelet treatment, whether aspirin, a P2Y12 inhibitor, or dual-antiplatelet therapy.

There were no significant differences in crude rates between groups in rates at 30 days of a composite endpoint of MACE, major bleeding as defined by the International Society on Thrombosis and Haemostasis, or net adverse clinical events (NACE), a composite of adverse events that included MACE and major bleeding.

Relative risks for antiplatelet discontinuation remained generally low even after multiple stratifications performed to explore different variables, including the types of antiplatelet therapy being taken at the time of discontinuation, the types of noncardiac surgery performed, and the duration of discontinuation.

Of these variables, the interval of discontinuation appeared to be most relevant. Antiplatelet discontinuation of 3 days or less appeared to be associated with a higher risk of bleeding, although the difference did not reach significance. Discontinuations of 9 days or more were associated with increased risk of MACE, and this difference did reach statistical significance (hazard ratio, 3.38; 95% confidence interval, 1.36-8.38).

“Discontinuation of antiplatelet therapy for a period of 4-8 days appears to be optimal,” Dr. Kim said.

In general, risk of MACE, major bleeding, or NACE could not be linked to type of surgery, with the exception of intra-abdominal surgery. For this procedure, there appeared to be a lower risk of MACE in those who discontinued relative to those who remained on antiplatelet therapy, Dr. Kim reported.

Importantly, because of the fact that the decision to stop antiplatelet treatment was made by treating physicians, the characteristics of those who discontinued or remained on antiplatelet therapy differed meaningfully. Specifically, those in the discontinuation group were younger and were less likely to have additional risks for thrombotic events such as diabetes or chronic kidney disease. In those who discontinued antiplatelets, the average time since PCI was 23 months versus 16 months in the continuation group.

In addition, “more of the patients underwent higher-risk surgeries in the discontinuation group,” Dr. Kim added.

Relative rates of MACE and NACE remained similar even after risk adjustment, but Dr. Kim advised that the data should be “interpreted cautiously” because of the retrospective nature of the analysis.

A panel of experts invited to comment on the presentation agreed. These data were considered reassuring for clinicians considering an interruption of antiplatelet therapy following PCI with a second-generation DES, but there was uncertainty about their value for defining which patients are the best candidates.

The decision to discontinue antiplatelet drugs for noncardiac surgery is an important and common dilemma, but these data might be best characterized as “a testament to Korean cardiologists making good decisions,” said David J. Moliterno, MD, chairman of the department of medicine at University of Kentucky Health Care, Lexington.

Dr. Kim reported no potential financial conflicts of interest.

NATIONAL HARBOR, MD. – Following a percutaneous intervention with a second-generation drug-eluting stent, a judicious interruption of antiplatelet therapy for noncardiac surgery does not increase risk of net adverse clinical events, according to a large dataset presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

Ted Bosworth/MDedge News

Drawn from a multicenter registry in South Korea, it is likely that those in whom antiplatelet therapy was stopped during the perioperative period were at a lower relative risk, but the data remain reassuring, according to Jung-Sun Kim, MD, PhD, professor of medicine at Yonsei University, Seoul, South Korea.

In the registry of patients with a second-generation drug-eluting stent (DES) undergoing noncardiac surgery, “antiplatelet therapy was discontinued in almost half of the patients,” Dr. Kim reported. When these patients were compared with those who did not discontinue antiplatelet therapy, the data, called an “exploratory analysis,” suggested “no increased risk” of a composite of major adverse cardiac events (MACE) or major bleeding.

The retrospective analysis involved 3,582 percutaneous intervention (PCI) patients who had received a second-generation DES and subsequently underwent noncardiac surgery. In 1,750 of these patients, antiplatelet therapy was temporarily discontinued. The remaining 1,832 remained on some form of antiplatelet treatment, whether aspirin, a P2Y12 inhibitor, or dual-antiplatelet therapy.

There were no significant differences in crude rates between groups in rates at 30 days of a composite endpoint of MACE, major bleeding as defined by the International Society on Thrombosis and Haemostasis, or net adverse clinical events (NACE), a composite of adverse events that included MACE and major bleeding.

Relative risks for antiplatelet discontinuation remained generally low even after multiple stratifications performed to explore different variables, including the types of antiplatelet therapy being taken at the time of discontinuation, the types of noncardiac surgery performed, and the duration of discontinuation.

Of these variables, the interval of discontinuation appeared to be most relevant. Antiplatelet discontinuation of 3 days or less appeared to be associated with a higher risk of bleeding, although the difference did not reach significance. Discontinuations of 9 days or more were associated with increased risk of MACE, and this difference did reach statistical significance (hazard ratio, 3.38; 95% confidence interval, 1.36-8.38).

“Discontinuation of antiplatelet therapy for a period of 4-8 days appears to be optimal,” Dr. Kim said.

In general, risk of MACE, major bleeding, or NACE could not be linked to type of surgery, with the exception of intra-abdominal surgery. For this procedure, there appeared to be a lower risk of MACE in those who discontinued relative to those who remained on antiplatelet therapy, Dr. Kim reported.

Importantly, because of the fact that the decision to stop antiplatelet treatment was made by treating physicians, the characteristics of those who discontinued or remained on antiplatelet therapy differed meaningfully. Specifically, those in the discontinuation group were younger and were less likely to have additional risks for thrombotic events such as diabetes or chronic kidney disease. In those who discontinued antiplatelets, the average time since PCI was 23 months versus 16 months in the continuation group.

In addition, “more of the patients underwent higher-risk surgeries in the discontinuation group,” Dr. Kim added.

Relative rates of MACE and NACE remained similar even after risk adjustment, but Dr. Kim advised that the data should be “interpreted cautiously” because of the retrospective nature of the analysis.

A panel of experts invited to comment on the presentation agreed. These data were considered reassuring for clinicians considering an interruption of antiplatelet therapy following PCI with a second-generation DES, but there was uncertainty about their value for defining which patients are the best candidates.

The decision to discontinue antiplatelet drugs for noncardiac surgery is an important and common dilemma, but these data might be best characterized as “a testament to Korean cardiologists making good decisions,” said David J. Moliterno, MD, chairman of the department of medicine at University of Kentucky Health Care, Lexington.

Dr. Kim reported no potential financial conflicts of interest.

NATIONAL HARBOR, MD. – If positive, a major ongoing phase 3 trial of CSL112, an agent designed to promote efflux of cholesterol from macrophages, is positioned to prove the HDL hypothesis, according to an outline of the rationale of the trial at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

“Twenty papers now show better efflux means better outcomes independent of standard risk factors” and “we know this drug improves efflux,” explained C. Michael Gibson, MD, an interventional cardiologist at Beth Israel Deaconess Hospital, Boston.

The HDL hypothesis was derived from the Framingham Heart Study, which correlated high levels of HDL cholesterol with a reduced risk of adverse cardiovascular (CV) outcomes, according to Dr. Gibson. Just as elevated LDL proved to be a treatable risk factor for CV events, reduced HDL was the target of numerous trials to achieve the same types of benefits.

All have failed.

The problem has been in seeing HDL as a number without addressing its function, Dr. Gibson said. In essence, he believes “the HDL hypothesis not been really tested to date.”

CSL112 is a novel formulation of apolipoprotein A-1 (apoA-1) that has been purified from human plasma and reconstituted to form HDL. In the experimental and clinical setting, including the AEGIS I pilot study, weekly infusions of CSL112 have been associated with a degree of cholesterol efflux that predicts major CV risk reductions.

At the same time that the multinational event-driven AEGIS II trial will determine whether cholesterol efflux with CSL112 does translate into protection from CV events, it will also examine the HDL side of the lipid equation. Dr. Gibson said that it is specifically designed to circumvent the weaknesses of previous efforts to target HDL for reducing CV risk.

“The previous studies were conducted in the wrong patients with the wrong drugs given in the wrong doses at the wrong times,” said Dr. Gibson, who is also professor of medicine at Harvard Medical School, Boston.

One major difference from previous trials is that AEGIS II is enrolling patients with an acute coronary syndrome rather than stable atherosclerosis. Many of those being enrolled have had a recent event. Also, rather than raising HDL, the goal of CSL112 is to increase cholesterol efflux, which is now considered to be the key function of HDL. Furthermore, the time frame for the primary outcome, which is a composite of major adverse cardiac outcomes (MACE), is 90 days rather than several years.

In patients with ACS, “it is the early period of vulnerability where efflux of cholesterol really appears to have the greatest influence on outcomes,” Dr. Gibson explained.

The failure of previous efforts to treat HDL now appears to be based on an incomplete understanding of the goals, according to Dr. Gibson. The doomed cholesteryl ester transfer protein (CETP) drugs, for example, effectively increased HDL levels, but generated a form of HDL that “was not all that functional.”

He noted that niacin raises HDL but has off-target effects. Apo-A1 Milano, a mutant variation of apo-A1, is now understood to reduce the endogenous form, which Dr. Gibson said might explain its counterproductive effect on CV protection.

Using a garbage truck analogy to explain the growing appreciation of factors involved in cholesterol accumulation in the macrophage, Dr. Gibson characterized ABCA1, a transporter protein sitting on the surface of the macrophage, as the loader. He described LCAT (lecithin-cholesterol acyltransferase), an enzyme that converts cholesterol into cholesteryl ester, as the compactor. He sees CRL112 as an empty garbage truck sent into the macrophage to reverse the process.

“We are moving beyond thinking of HDL as a number to try to better appreciate its function,” Dr. Gibson said.

The AEGIS II trial was opened in March of 2018. It has a planned enrollment of 17,400 patients, with an estimated completion date of October 2021.

Dr. Gibson reports financial relationships with Bayer, Janssen, Johnson & Johnson, and CSL Behring, the sponsor of the AEGIS II trial.

NATIONAL HARBOR, MD. – If positive, a major ongoing phase 3 trial of CSL112, an agent designed to promote efflux of cholesterol from macrophages, is positioned to prove the HDL hypothesis, according to an outline of the rationale of the trial at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

“Twenty papers now show better efflux means better outcomes independent of standard risk factors” and “we know this drug improves efflux,” explained C. Michael Gibson, MD, an interventional cardiologist at Beth Israel Deaconess Hospital, Boston.

The HDL hypothesis was derived from the Framingham Heart Study, which correlated high levels of HDL cholesterol with a reduced risk of adverse cardiovascular (CV) outcomes, according to Dr. Gibson. Just as elevated LDL proved to be a treatable risk factor for CV events, reduced HDL was the target of numerous trials to achieve the same types of benefits.

All have failed.

The problem has been in seeing HDL as a number without addressing its function, Dr. Gibson said. In essence, he believes “the HDL hypothesis not been really tested to date.”

CSL112 is a novel formulation of apolipoprotein A-1 (apoA-1) that has been purified from human plasma and reconstituted to form HDL. In the experimental and clinical setting, including the AEGIS I pilot study, weekly infusions of CSL112 have been associated with a degree of cholesterol efflux that predicts major CV risk reductions.

At the same time that the multinational event-driven AEGIS II trial will determine whether cholesterol efflux with CSL112 does translate into protection from CV events, it will also examine the HDL side of the lipid equation. Dr. Gibson said that it is specifically designed to circumvent the weaknesses of previous efforts to target HDL for reducing CV risk.

“The previous studies were conducted in the wrong patients with the wrong drugs given in the wrong doses at the wrong times,” said Dr. Gibson, who is also professor of medicine at Harvard Medical School, Boston.

One major difference from previous trials is that AEGIS II is enrolling patients with an acute coronary syndrome rather than stable atherosclerosis. Many of those being enrolled have had a recent event. Also, rather than raising HDL, the goal of CSL112 is to increase cholesterol efflux, which is now considered to be the key function of HDL. Furthermore, the time frame for the primary outcome, which is a composite of major adverse cardiac outcomes (MACE), is 90 days rather than several years.

In patients with ACS, “it is the early period of vulnerability where efflux of cholesterol really appears to have the greatest influence on outcomes,” Dr. Gibson explained.

The failure of previous efforts to treat HDL now appears to be based on an incomplete understanding of the goals, according to Dr. Gibson. The doomed cholesteryl ester transfer protein (CETP) drugs, for example, effectively increased HDL levels, but generated a form of HDL that “was not all that functional.”

He noted that niacin raises HDL but has off-target effects. Apo-A1 Milano, a mutant variation of apo-A1, is now understood to reduce the endogenous form, which Dr. Gibson said might explain its counterproductive effect on CV protection.

Using a garbage truck analogy to explain the growing appreciation of factors involved in cholesterol accumulation in the macrophage, Dr. Gibson characterized ABCA1, a transporter protein sitting on the surface of the macrophage, as the loader. He described LCAT (lecithin-cholesterol acyltransferase), an enzyme that converts cholesterol into cholesteryl ester, as the compactor. He sees CRL112 as an empty garbage truck sent into the macrophage to reverse the process.

“We are moving beyond thinking of HDL as a number to try to better appreciate its function,” Dr. Gibson said.

The AEGIS II trial was opened in March of 2018. It has a planned enrollment of 17,400 patients, with an estimated completion date of October 2021.

Dr. Gibson reports financial relationships with Bayer, Janssen, Johnson & Johnson, and CSL Behring, the sponsor of the AEGIS II trial.

NATIONAL HARBOR, MD. – If positive, a major ongoing phase 3 trial of CSL112, an agent designed to promote efflux of cholesterol from macrophages, is positioned to prove the HDL hypothesis, according to an outline of the rationale of the trial at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

“Twenty papers now show better efflux means better outcomes independent of standard risk factors” and “we know this drug improves efflux,” explained C. Michael Gibson, MD, an interventional cardiologist at Beth Israel Deaconess Hospital, Boston.

The HDL hypothesis was derived from the Framingham Heart Study, which correlated high levels of HDL cholesterol with a reduced risk of adverse cardiovascular (CV) outcomes, according to Dr. Gibson. Just as elevated LDL proved to be a treatable risk factor for CV events, reduced HDL was the target of numerous trials to achieve the same types of benefits.

All have failed.

The problem has been in seeing HDL as a number without addressing its function, Dr. Gibson said. In essence, he believes “the HDL hypothesis not been really tested to date.”

CSL112 is a novel formulation of apolipoprotein A-1 (apoA-1) that has been purified from human plasma and reconstituted to form HDL. In the experimental and clinical setting, including the AEGIS I pilot study, weekly infusions of CSL112 have been associated with a degree of cholesterol efflux that predicts major CV risk reductions.

At the same time that the multinational event-driven AEGIS II trial will determine whether cholesterol efflux with CSL112 does translate into protection from CV events, it will also examine the HDL side of the lipid equation. Dr. Gibson said that it is specifically designed to circumvent the weaknesses of previous efforts to target HDL for reducing CV risk.

“The previous studies were conducted in the wrong patients with the wrong drugs given in the wrong doses at the wrong times,” said Dr. Gibson, who is also professor of medicine at Harvard Medical School, Boston.

One major difference from previous trials is that AEGIS II is enrolling patients with an acute coronary syndrome rather than stable atherosclerosis. Many of those being enrolled have had a recent event. Also, rather than raising HDL, the goal of CSL112 is to increase cholesterol efflux, which is now considered to be the key function of HDL. Furthermore, the time frame for the primary outcome, which is a composite of major adverse cardiac outcomes (MACE), is 90 days rather than several years.

In patients with ACS, “it is the early period of vulnerability where efflux of cholesterol really appears to have the greatest influence on outcomes,” Dr. Gibson explained.

The failure of previous efforts to treat HDL now appears to be based on an incomplete understanding of the goals, according to Dr. Gibson. The doomed cholesteryl ester transfer protein (CETP) drugs, for example, effectively increased HDL levels, but generated a form of HDL that “was not all that functional.”

He noted that niacin raises HDL but has off-target effects. Apo-A1 Milano, a mutant variation of apo-A1, is now understood to reduce the endogenous form, which Dr. Gibson said might explain its counterproductive effect on CV protection.

Using a garbage truck analogy to explain the growing appreciation of factors involved in cholesterol accumulation in the macrophage, Dr. Gibson characterized ABCA1, a transporter protein sitting on the surface of the macrophage, as the loader. He described LCAT (lecithin-cholesterol acyltransferase), an enzyme that converts cholesterol into cholesteryl ester, as the compactor. He sees CRL112 as an empty garbage truck sent into the macrophage to reverse the process.

“We are moving beyond thinking of HDL as a number to try to better appreciate its function,” Dr. Gibson said.

The AEGIS II trial was opened in March of 2018. It has a planned enrollment of 17,400 patients, with an estimated completion date of October 2021.

Dr. Gibson reports financial relationships with Bayer, Janssen, Johnson & Johnson, and CSL Behring, the sponsor of the AEGIS II trial.

NATIONAL HARBOR, MD. – Just a month before results from the first of several new pivotal trials with a renal denervation device are to be presented, a Food and Drug Administration medical officer speaking at CRT 2020 sponsored by MedStar Heart & Vascular Institute explained which data will most attract the scrutiny of regulators.

Ted Bosworth/MDedge News

“The FDA is very interested in these devices. We recognize that there is a clinical need, but a reasonable benefit-to-risk relationship has to be established,” said Meir Shinnar, MD, PhD, who works in the division of cardiac devices in the FDA’s Office of Device Evaluation.

The field of renal denervation is expected to heat up again if the results of the SPYRAL HTN OFF MED pivotal trial, planned as a late-breaking presentation at the annual meeting of the American College of Cardiology in March 2020, are positive. However, long-term safety will remain a concern, and positive results will not diminish the rigor with which the relative safety and efficacy of other devices in late stages of clinical testing are evaluated.

“The safety profile is unique to the device design and the procedural technique,” Dr. Shinnar said. For example, vascular injury from the energy employed for denervation, whether radiofrequency or another modality, is an important theoretical risk. A minor initial injury might have no immediate consequences but pose major risks if it leads to altered kidney function over time.

“Most of the follow-up data we have now [with renal denervation devices] is about 1-3 years, but I think long-term safety requires a minimum of 5 years of safety data,” Dr. Shinnar said. “We do not expect all that data to be available at the time of approval, but postmarketing studies will be needed.”

Almost 6 years after the SYMPLICITY HTN-3 trial failed to show a significant reduction in blood pressure among patients with resistant hypertension treated with renal denervation rather than a sham procedure (N Engl J Med 2014;370:1393-401), this treatment is again considered promising. The surprising SYMPLICITY HTN-3 result led to several revisions in technique based on the suspicion that denervation was inadequate.

However, the basic principles remain unchanged. For renal denervation, SPYRAL HTN OFF MED, like the SYMPLICITY HTN 3 study, is employing the Symplicity (Medtronic) device, which has been approved in 50 countries but not in the United States, Canada, or Japan.

SPYRAL HTN OFF MED is designed to provide a very straightforward test of efficacy. Unlike SYMPLICITY HTN-3, which permitted patients to remain on their antihypertensive medications, patients in SPYRAL HTN OFF MED will be tested in the absence of drug therapy (a trial with adjunctive antihypertensive drugs, SPYRAL HTN ON MED, is ongoing). This is a design feature that is relevant to regulatory evaluation.

Although not speaking about the SPYRAL HTN OFF MED trial specifically, Dr. Shinnar noted that “the bar is considered to be higher for a first-line indication than when a device is used as an adjunctive to drug therapy.”

Whether used with or without medications, devices are not likely to receive approval without showing a durable benefit. Dr. Shinnar, citing the surgical studies in which blood pressure control was lost 1-2 years after denervation, said 12 months is now considered a “preferred” length of follow-up to confirm efficacy.

If renal denervation moves forward as a result of the new wave of phase 3 trials, there will still be many unanswered questions, according to Dr. Shinnar, who noted that the FDA convened an advisory committee in December 2018 to gather expert opinion about meaningful safety as well as efficacy endpoints for this modality. One will be determining which populations, defined by age, gender, or phenotype, most benefit.

It also remains unclear whether the first approval will create a standard to which subsequent devices should be compared, according to Dr. Shinnar. Although the FDA recognizes blood pressure reductions as an acceptable endpoint, he believes that documentation of the impact on clinical events will be sought in postmarketing analyses.

“All of the denervation modalities involve class 3 devices that require significant data,” Dr. Shinnar cautioned.

Even if the SPYRAL HTN OFF MED trial is positive on the basis of efficacy, it does not guarantee regulatory approval. Dr. Shinnar described a multifaceted approach to defining an acceptable risk-to-benefit ratio from approved devices, and warned that several points regarding the evaluation of renal denervation devices by the FDA are still being debated internally.

Dr. Shinnar reported no potential financial conflicts of interest.

NATIONAL HARBOR, MD. – Just a month before results from the first of several new pivotal trials with a renal denervation device are to be presented, a Food and Drug Administration medical officer speaking at CRT 2020 sponsored by MedStar Heart & Vascular Institute explained which data will most attract the scrutiny of regulators.

Ted Bosworth/MDedge News

“The FDA is very interested in these devices. We recognize that there is a clinical need, but a reasonable benefit-to-risk relationship has to be established,” said Meir Shinnar, MD, PhD, who works in the division of cardiac devices in the FDA’s Office of Device Evaluation.

The field of renal denervation is expected to heat up again if the results of the SPYRAL HTN OFF MED pivotal trial, planned as a late-breaking presentation at the annual meeting of the American College of Cardiology in March 2020, are positive. However, long-term safety will remain a concern, and positive results will not diminish the rigor with which the relative safety and efficacy of other devices in late stages of clinical testing are evaluated.

“The safety profile is unique to the device design and the procedural technique,” Dr. Shinnar said. For example, vascular injury from the energy employed for denervation, whether radiofrequency or another modality, is an important theoretical risk. A minor initial injury might have no immediate consequences but pose major risks if it leads to altered kidney function over time.

“Most of the follow-up data we have now [with renal denervation devices] is about 1-3 years, but I think long-term safety requires a minimum of 5 years of safety data,” Dr. Shinnar said. “We do not expect all that data to be available at the time of approval, but postmarketing studies will be needed.”

Almost 6 years after the SYMPLICITY HTN-3 trial failed to show a significant reduction in blood pressure among patients with resistant hypertension treated with renal denervation rather than a sham procedure (N Engl J Med 2014;370:1393-401), this treatment is again considered promising. The surprising SYMPLICITY HTN-3 result led to several revisions in technique based on the suspicion that denervation was inadequate.

However, the basic principles remain unchanged. For renal denervation, SPYRAL HTN OFF MED, like the SYMPLICITY HTN 3 study, is employing the Symplicity (Medtronic) device, which has been approved in 50 countries but not in the United States, Canada, or Japan.

SPYRAL HTN OFF MED is designed to provide a very straightforward test of efficacy. Unlike SYMPLICITY HTN-3, which permitted patients to remain on their antihypertensive medications, patients in SPYRAL HTN OFF MED will be tested in the absence of drug therapy (a trial with adjunctive antihypertensive drugs, SPYRAL HTN ON MED, is ongoing). This is a design feature that is relevant to regulatory evaluation.

Although not speaking about the SPYRAL HTN OFF MED trial specifically, Dr. Shinnar noted that “the bar is considered to be higher for a first-line indication than when a device is used as an adjunctive to drug therapy.”

Whether used with or without medications, devices are not likely to receive approval without showing a durable benefit. Dr. Shinnar, citing the surgical studies in which blood pressure control was lost 1-2 years after denervation, said 12 months is now considered a “preferred” length of follow-up to confirm efficacy.

If renal denervation moves forward as a result of the new wave of phase 3 trials, there will still be many unanswered questions, according to Dr. Shinnar, who noted that the FDA convened an advisory committee in December 2018 to gather expert opinion about meaningful safety as well as efficacy endpoints for this modality. One will be determining which populations, defined by age, gender, or phenotype, most benefit.

It also remains unclear whether the first approval will create a standard to which subsequent devices should be compared, according to Dr. Shinnar. Although the FDA recognizes blood pressure reductions as an acceptable endpoint, he believes that documentation of the impact on clinical events will be sought in postmarketing analyses.

“All of the denervation modalities involve class 3 devices that require significant data,” Dr. Shinnar cautioned.

Even if the SPYRAL HTN OFF MED trial is positive on the basis of efficacy, it does not guarantee regulatory approval. Dr. Shinnar described a multifaceted approach to defining an acceptable risk-to-benefit ratio from approved devices, and warned that several points regarding the evaluation of renal denervation devices by the FDA are still being debated internally.

Dr. Shinnar reported no potential financial conflicts of interest.

NATIONAL HARBOR, MD. – Just a month before results from the first of several new pivotal trials with a renal denervation device are to be presented, a Food and Drug Administration medical officer speaking at CRT 2020 sponsored by MedStar Heart & Vascular Institute explained which data will most attract the scrutiny of regulators.

Ted Bosworth/MDedge News

“The FDA is very interested in these devices. We recognize that there is a clinical need, but a reasonable benefit-to-risk relationship has to be established,” said Meir Shinnar, MD, PhD, who works in the division of cardiac devices in the FDA’s Office of Device Evaluation.

The field of renal denervation is expected to heat up again if the results of the SPYRAL HTN OFF MED pivotal trial, planned as a late-breaking presentation at the annual meeting of the American College of Cardiology in March 2020, are positive. However, long-term safety will remain a concern, and positive results will not diminish the rigor with which the relative safety and efficacy of other devices in late stages of clinical testing are evaluated.

“The safety profile is unique to the device design and the procedural technique,” Dr. Shinnar said. For example, vascular injury from the energy employed for denervation, whether radiofrequency or another modality, is an important theoretical risk. A minor initial injury might have no immediate consequences but pose major risks if it leads to altered kidney function over time.

“Most of the follow-up data we have now [with renal denervation devices] is about 1-3 years, but I think long-term safety requires a minimum of 5 years of safety data,” Dr. Shinnar said. “We do not expect all that data to be available at the time of approval, but postmarketing studies will be needed.”

Almost 6 years after the SYMPLICITY HTN-3 trial failed to show a significant reduction in blood pressure among patients with resistant hypertension treated with renal denervation rather than a sham procedure (N Engl J Med 2014;370:1393-401), this treatment is again considered promising. The surprising SYMPLICITY HTN-3 result led to several revisions in technique based on the suspicion that denervation was inadequate.

However, the basic principles remain unchanged. For renal denervation, SPYRAL HTN OFF MED, like the SYMPLICITY HTN 3 study, is employing the Symplicity (Medtronic) device, which has been approved in 50 countries but not in the United States, Canada, or Japan.

SPYRAL HTN OFF MED is designed to provide a very straightforward test of efficacy. Unlike SYMPLICITY HTN-3, which permitted patients to remain on their antihypertensive medications, patients in SPYRAL HTN OFF MED will be tested in the absence of drug therapy (a trial with adjunctive antihypertensive drugs, SPYRAL HTN ON MED, is ongoing). This is a design feature that is relevant to regulatory evaluation.

Although not speaking about the SPYRAL HTN OFF MED trial specifically, Dr. Shinnar noted that “the bar is considered to be higher for a first-line indication than when a device is used as an adjunctive to drug therapy.”

Whether used with or without medications, devices are not likely to receive approval without showing a durable benefit. Dr. Shinnar, citing the surgical studies in which blood pressure control was lost 1-2 years after denervation, said 12 months is now considered a “preferred” length of follow-up to confirm efficacy.

If renal denervation moves forward as a result of the new wave of phase 3 trials, there will still be many unanswered questions, according to Dr. Shinnar, who noted that the FDA convened an advisory committee in December 2018 to gather expert opinion about meaningful safety as well as efficacy endpoints for this modality. One will be determining which populations, defined by age, gender, or phenotype, most benefit.

It also remains unclear whether the first approval will create a standard to which subsequent devices should be compared, according to Dr. Shinnar. Although the FDA recognizes blood pressure reductions as an acceptable endpoint, he believes that documentation of the impact on clinical events will be sought in postmarketing analyses.

“All of the denervation modalities involve class 3 devices that require significant data,” Dr. Shinnar cautioned.

Even if the SPYRAL HTN OFF MED trial is positive on the basis of efficacy, it does not guarantee regulatory approval. Dr. Shinnar described a multifaceted approach to defining an acceptable risk-to-benefit ratio from approved devices, and warned that several points regarding the evaluation of renal denervation devices by the FDA are still being debated internally.

Dr. Shinnar reported no potential financial conflicts of interest.

NATIONAL HARBOR, MD. – Of characteristics that might predict which patients with resistant hypertension will respond to carotid body ablation, the relative activity of the carotid body organ itself might be critical for moving this technology forward, an investigator on a first-in-man study suggests.

The study, first presented in 2018 at the European Society of Cardiology congress, showed carotid body ablation resulted in significant but modest reductions in blood pressure in patients with resistant hypertension.

Ted Bosworth/MDedge News

For many reasons, the carotid body is an attractive target for sustained or indefinite control of resistant hypertension, but median systolic blood pressure reductions following ultrasound ablation were highly variable in the first-in-man study, according to Felix Mahfoud, MD, of Saarland University Hospital in Homburg, Germany, a coinvestigator on the study who discussed the findings at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

Of several strategies being pursued to separate those most likely to gain a major benefit, simply measuring carotid body activity is now emerging as particularly promising.

“Patients with a high degree of carotid body activity had a significantly larger fall in blood pressure versus all other methods of grouping patients,” Dr. Mahfoud reported.

The carotid body is a “grain-size” organ of about 2 mm in size that sits on the carotid bifurcation. It communicates directly with the brain to alter sympathetic activity in response to changing levels of such physiologic variable as oxygen, carbon dioxide, and pH, according to Dr. Mahfoud.

In a 2016 proof-of-principle study conducted in resistant hypertension patients, surgical resection of the carotid body was associated with a median 18–mm Hg reduction in systolic blood pressure (SBP) on 24-hour ambulatory monitoring that was sustained through 24 months (Narkiewicz K et al. JACC Basic Transl Sci. 2016;29:313-24).

Subsequently, ultrasound ablation of the carotid body was by way of a transcatheter approach. Dr. Mahfoud’s unpublished first-in-man study, conducted in 2018 enrolled 38 patients with resistant hypertension. The median reductions from baseline of 7-8 mm Hg at 1, 3, and 6 months were significant (P less than .01), but the benefit was disappointingly modest.

However, the variability was large. Some patients achieved SBP reductions of up to 20 mm Hg at 6 months, prompting additional analyses to understand if the best responders could be identified. When compared to the mean reduction of 7 mm Hg at 6 months, this represented a 13–mm Hg additional reduction. There are now several potential approaches being considered.

In addition to carotid body activity, which is readily measured and has substantial potential to serve as a routine selection criterion, isolated systolic hypertension (ISH) was also found to be a discriminator for response. For those with ISH, which Dr. Mahfoud noted is also characterized as “stiff arteries,” SBP reductions at 6 months were negligible, but in those without ISH, the median reduction from baseline was 11 mm Hg.

Further investigations are now planned to evaluate potential predictors of response, according to Dr. Mahfoud. He believes carotid body ablation might have advantages over alternatives, including other experimental therapies, in at least some patients.

To deliver ultrasound ablation in the first-in-man study, a propriety catheter (Cibiem transvenous system) was advanced through the jugular vein guided with intravascular ultrasound. When the carotid body was reached, two to three ultrasound ablations of 8-12 seconds each were applied. The procedure time was 20-30 minutes.

Initially, an arterial approach to the carotid body was used. However, after a transient ischemic attack early in the series, the approach was switched to the jugular vein. There have been no serious subsequent procedural-related complications since.

Although the median SBP reductions were modest, they were not insignificant in a population selected for severe resistant hypertension. The median SBP at entry was 180 mm Hg in patients taking a median of 4.5 antihypertensive drugs, according to Dr. Mahfoud.

In other words, this approach still retains promise for selected patients if larger studies demonstrate that response can be predicted, and the data continue to support tolerability.

A venous approach to the carotid body with intravascular ultrasound guidance and therapeutic ultrasound appears “to offer a safe and effective treatment option in resistant hypertension,” according to Dr. Mahfoud. “A companion diagnostic test is being developed to determine whether patients are likely to respond to this therapy.”

Dr. Mahfoud reports financial relationships with Medtronic, St. Jude, and ReCor.

This article was updated to clarify the study details and correct misspellings of the presenter's name.

SOURCE: CRT 2020.

NATIONAL HARBOR, MD. – Of characteristics that might predict which patients with resistant hypertension will respond to carotid body ablation, the relative activity of the carotid body organ itself might be critical for moving this technology forward, an investigator on a first-in-man study suggests.

The study, first presented in 2018 at the European Society of Cardiology congress, showed carotid body ablation resulted in significant but modest reductions in blood pressure in patients with resistant hypertension.

Ted Bosworth/MDedge News

For many reasons, the carotid body is an attractive target for sustained or indefinite control of resistant hypertension, but median systolic blood pressure reductions following ultrasound ablation were highly variable in the first-in-man study, according to Felix Mahfoud, MD, of Saarland University Hospital in Homburg, Germany, a coinvestigator on the study who discussed the findings at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

Of several strategies being pursued to separate those most likely to gain a major benefit, simply measuring carotid body activity is now emerging as particularly promising.

“Patients with a high degree of carotid body activity had a significantly larger fall in blood pressure versus all other methods of grouping patients,” Dr. Mahfoud reported.

The carotid body is a “grain-size” organ of about 2 mm in size that sits on the carotid bifurcation. It communicates directly with the brain to alter sympathetic activity in response to changing levels of such physiologic variable as oxygen, carbon dioxide, and pH, according to Dr. Mahfoud.

In a 2016 proof-of-principle study conducted in resistant hypertension patients, surgical resection of the carotid body was associated with a median 18–mm Hg reduction in systolic blood pressure (SBP) on 24-hour ambulatory monitoring that was sustained through 24 months (Narkiewicz K et al. JACC Basic Transl Sci. 2016;29:313-24).

Subsequently, ultrasound ablation of the carotid body was by way of a transcatheter approach. Dr. Mahfoud’s unpublished first-in-man study, conducted in 2018 enrolled 38 patients with resistant hypertension. The median reductions from baseline of 7-8 mm Hg at 1, 3, and 6 months were significant (P less than .01), but the benefit was disappointingly modest.

However, the variability was large. Some patients achieved SBP reductions of up to 20 mm Hg at 6 months, prompting additional analyses to understand if the best responders could be identified. When compared to the mean reduction of 7 mm Hg at 6 months, this represented a 13–mm Hg additional reduction. There are now several potential approaches being considered.

In addition to carotid body activity, which is readily measured and has substantial potential to serve as a routine selection criterion, isolated systolic hypertension (ISH) was also found to be a discriminator for response. For those with ISH, which Dr. Mahfoud noted is also characterized as “stiff arteries,” SBP reductions at 6 months were negligible, but in those without ISH, the median reduction from baseline was 11 mm Hg.

Further investigations are now planned to evaluate potential predictors of response, according to Dr. Mahfoud. He believes carotid body ablation might have advantages over alternatives, including other experimental therapies, in at least some patients.

To deliver ultrasound ablation in the first-in-man study, a propriety catheter (Cibiem transvenous system) was advanced through the jugular vein guided with intravascular ultrasound. When the carotid body was reached, two to three ultrasound ablations of 8-12 seconds each were applied. The procedure time was 20-30 minutes.

Initially, an arterial approach to the carotid body was used. However, after a transient ischemic attack early in the series, the approach was switched to the jugular vein. There have been no serious subsequent procedural-related complications since.

Although the median SBP reductions were modest, they were not insignificant in a population selected for severe resistant hypertension. The median SBP at entry was 180 mm Hg in patients taking a median of 4.5 antihypertensive drugs, according to Dr. Mahfoud.

In other words, this approach still retains promise for selected patients if larger studies demonstrate that response can be predicted, and the data continue to support tolerability.

A venous approach to the carotid body with intravascular ultrasound guidance and therapeutic ultrasound appears “to offer a safe and effective treatment option in resistant hypertension,” according to Dr. Mahfoud. “A companion diagnostic test is being developed to determine whether patients are likely to respond to this therapy.”

Dr. Mahfoud reports financial relationships with Medtronic, St. Jude, and ReCor.

This article was updated to clarify the study details and correct misspellings of the presenter's name.

SOURCE: CRT 2020.

NATIONAL HARBOR, MD. – Of characteristics that might predict which patients with resistant hypertension will respond to carotid body ablation, the relative activity of the carotid body organ itself might be critical for moving this technology forward, an investigator on a first-in-man study suggests.

The study, first presented in 2018 at the European Society of Cardiology congress, showed carotid body ablation resulted in significant but modest reductions in blood pressure in patients with resistant hypertension.

Ted Bosworth/MDedge News

For many reasons, the carotid body is an attractive target for sustained or indefinite control of resistant hypertension, but median systolic blood pressure reductions following ultrasound ablation were highly variable in the first-in-man study, according to Felix Mahfoud, MD, of Saarland University Hospital in Homburg, Germany, a coinvestigator on the study who discussed the findings at CRT 2020 sponsored by MedStar Heart & Vascular Institute.

Of several strategies being pursued to separate those most likely to gain a major benefit, simply measuring carotid body activity is now emerging as particularly promising.

“Patients with a high degree of carotid body activity had a significantly larger fall in blood pressure versus all other methods of grouping patients,” Dr. Mahfoud reported.

The carotid body is a “grain-size” organ of about 2 mm in size that sits on the carotid bifurcation. It communicates directly with the brain to alter sympathetic activity in response to changing levels of such physiologic variable as oxygen, carbon dioxide, and pH, according to Dr. Mahfoud.

In a 2016 proof-of-principle study conducted in resistant hypertension patients, surgical resection of the carotid body was associated with a median 18–mm Hg reduction in systolic blood pressure (SBP) on 24-hour ambulatory monitoring that was sustained through 24 months (Narkiewicz K et al. JACC Basic Transl Sci. 2016;29:313-24).

Subsequently, ultrasound ablation of the carotid body was by way of a transcatheter approach. Dr. Mahfoud’s unpublished first-in-man study, conducted in 2018 enrolled 38 patients with resistant hypertension. The median reductions from baseline of 7-8 mm Hg at 1, 3, and 6 months were significant (P less than .01), but the benefit was disappointingly modest.

However, the variability was large. Some patients achieved SBP reductions of up to 20 mm Hg at 6 months, prompting additional analyses to understand if the best responders could be identified. When compared to the mean reduction of 7 mm Hg at 6 months, this represented a 13–mm Hg additional reduction. There are now several potential approaches being considered.

In addition to carotid body activity, which is readily measured and has substantial potential to serve as a routine selection criterion, isolated systolic hypertension (ISH) was also found to be a discriminator for response. For those with ISH, which Dr. Mahfoud noted is also characterized as “stiff arteries,” SBP reductions at 6 months were negligible, but in those without ISH, the median reduction from baseline was 11 mm Hg.

Further investigations are now planned to evaluate potential predictors of response, according to Dr. Mahfoud. He believes carotid body ablation might have advantages over alternatives, including other experimental therapies, in at least some patients.

To deliver ultrasound ablation in the first-in-man study, a propriety catheter (Cibiem transvenous system) was advanced through the jugular vein guided with intravascular ultrasound. When the carotid body was reached, two to three ultrasound ablations of 8-12 seconds each were applied. The procedure time was 20-30 minutes.

Initially, an arterial approach to the carotid body was used. However, after a transient ischemic attack early in the series, the approach was switched to the jugular vein. There have been no serious subsequent procedural-related complications since.

Although the median SBP reductions were modest, they were not insignificant in a population selected for severe resistant hypertension. The median SBP at entry was 180 mm Hg in patients taking a median of 4.5 antihypertensive drugs, according to Dr. Mahfoud.

In other words, this approach still retains promise for selected patients if larger studies demonstrate that response can be predicted, and the data continue to support tolerability.

A venous approach to the carotid body with intravascular ultrasound guidance and therapeutic ultrasound appears “to offer a safe and effective treatment option in resistant hypertension,” according to Dr. Mahfoud. “A companion diagnostic test is being developed to determine whether patients are likely to respond to this therapy.”

Dr. Mahfoud reports financial relationships with Medtronic, St. Jude, and ReCor.

This article was updated to clarify the study details and correct misspellings of the presenter's name.

SOURCE: CRT 2020.