Cardiothoracic Surgery

SAN DIEGO – Among patients undergoing cardiac bypass surgery, perioperative use of corticosteroids did not alter the risk of acute kidney injury, results from a large randomized trial showed.

“Worldwide, over 20 million cardiac surgeries are done each year, but 4 million are complicated by acute kidney injury, and 200,000 are complicated by severe kidney injury treated with dialysis,” Dr. Amit X. Garg said during a press briefing at the annual meeting of the American Society of Nephrology. “So certainly people would benefit from a therapy to prevent acute kidney injury (AKI) and improve the safety of surgery.”

Dr. Garg, a nephrologist at the London Health Sciences Centre in London, Ontario, Canada, noted that cardiopulmonary bypass initiates a systemic inflammatory response syndrome, “which activates complement, inflammatory cytokines, and other inflammatory mediators, which in turn increases endothelial permeability, organ damage, and increased morbidity and mortality, including acute kidney injury.” Researchers are interested in corticosteroids, “because they suppress this inflammatory response. In other settings, such as acute glomerulonephritis, we successfully use corticosteroids to treat acute inflammation in the kidney,” he said.

In a study known as the Steroids in caRdiac Surgery Trial (SIRS), researchers at 79 centers in 18 countries set out to investigate if methylprednisolone alters the risk of acute kidney injury in patients undergoing cardiac surgery with cardiopulmonary bypass. Between June 2007 and December 2013, 7,286 patients were randomized to intravenous methylprednisolone 250 mg at anesthetic induction and 250 mg at initiation of coronary bypass, or placebo.

AKI was defined as a 0.3 mg/dL increase or greater in postoperative serum creatinine concentration from the preoperative concentration within 14 days following surgery, or a 50% increase from the preoperative value within 14 days following surgery. Secondary outcomes included different stages of AKI and receipt of acute dialysis in the 30 days following surgery. Patients, caregivers, and researchers were blinded to the treatment allocation.

Of the 7,286 patients, 3,647 received methylprednisolone and 3,639 received placebo. The mean age of patients was 60 years, 60% were men, 26% were diabetic, and 25% of patients had combined CABG and valve surgery.

The SIRS Investigators reported that the risk of AKI was similar among patients who received methylprednisolone and those who received placebo (40.9% vs. 39.5%, respectively; relative risk 1.03). Results were similar across multiple categorical definitions of AKI, including AKI or death (41.5% vs 40.2%; RR 1.03); AKI stage of 2 or greater (9.9% vs 9.9%; RR 1.01); AKI stage of 3 or greater (4% vs. 4.5%; RR .89), and being on acute dialysis (2.6% vs. 2.4%; RR 1.08).

“There was no benefit of steroids on the risk of AKI in those with or without preoperative chronic kidney disease,” Dr. Garg said. “The result was also not different in the subpopulation of patients with AKI as defined by Kidney Disease Improving Global Outcomes.” Results from SIRS “would suggest that patients undergoing cardiac surgery with cardiopulmonary bypass should not use prophylactic steroids to prevent AKI. When we consider the side effect profile, the most clinically relevant outcomes, and apply the GRADE framework [the Grading of Recommendations Assessment, Development, and Evaluation] to the available evidence, we would recommend that steroids not be used in this way, with a grade 1B recommendation.”

The study was sponsored by the Population Health Research Institute in Hamilton, Ontario and the Canadian Institutes of Health Research. Dr. Garg reported having no relevant financial disclosures for this study.

[email protected]

SAN DIEGO – Among patients undergoing cardiac bypass surgery, perioperative use of corticosteroids did not alter the risk of acute kidney injury, results from a large randomized trial showed.

“Worldwide, over 20 million cardiac surgeries are done each year, but 4 million are complicated by acute kidney injury, and 200,000 are complicated by severe kidney injury treated with dialysis,” Dr. Amit X. Garg said during a press briefing at the annual meeting of the American Society of Nephrology. “So certainly people would benefit from a therapy to prevent acute kidney injury (AKI) and improve the safety of surgery.”

Dr. Garg, a nephrologist at the London Health Sciences Centre in London, Ontario, Canada, noted that cardiopulmonary bypass initiates a systemic inflammatory response syndrome, “which activates complement, inflammatory cytokines, and other inflammatory mediators, which in turn increases endothelial permeability, organ damage, and increased morbidity and mortality, including acute kidney injury.” Researchers are interested in corticosteroids, “because they suppress this inflammatory response. In other settings, such as acute glomerulonephritis, we successfully use corticosteroids to treat acute inflammation in the kidney,” he said.

In a study known as the Steroids in caRdiac Surgery Trial (SIRS), researchers at 79 centers in 18 countries set out to investigate if methylprednisolone alters the risk of acute kidney injury in patients undergoing cardiac surgery with cardiopulmonary bypass. Between June 2007 and December 2013, 7,286 patients were randomized to intravenous methylprednisolone 250 mg at anesthetic induction and 250 mg at initiation of coronary bypass, or placebo.

AKI was defined as a 0.3 mg/dL increase or greater in postoperative serum creatinine concentration from the preoperative concentration within 14 days following surgery, or a 50% increase from the preoperative value within 14 days following surgery. Secondary outcomes included different stages of AKI and receipt of acute dialysis in the 30 days following surgery. Patients, caregivers, and researchers were blinded to the treatment allocation.

Of the 7,286 patients, 3,647 received methylprednisolone and 3,639 received placebo. The mean age of patients was 60 years, 60% were men, 26% were diabetic, and 25% of patients had combined CABG and valve surgery.

The SIRS Investigators reported that the risk of AKI was similar among patients who received methylprednisolone and those who received placebo (40.9% vs. 39.5%, respectively; relative risk 1.03). Results were similar across multiple categorical definitions of AKI, including AKI or death (41.5% vs 40.2%; RR 1.03); AKI stage of 2 or greater (9.9% vs 9.9%; RR 1.01); AKI stage of 3 or greater (4% vs. 4.5%; RR .89), and being on acute dialysis (2.6% vs. 2.4%; RR 1.08).

“There was no benefit of steroids on the risk of AKI in those with or without preoperative chronic kidney disease,” Dr. Garg said. “The result was also not different in the subpopulation of patients with AKI as defined by Kidney Disease Improving Global Outcomes.” Results from SIRS “would suggest that patients undergoing cardiac surgery with cardiopulmonary bypass should not use prophylactic steroids to prevent AKI. When we consider the side effect profile, the most clinically relevant outcomes, and apply the GRADE framework [the Grading of Recommendations Assessment, Development, and Evaluation] to the available evidence, we would recommend that steroids not be used in this way, with a grade 1B recommendation.”

The study was sponsored by the Population Health Research Institute in Hamilton, Ontario and the Canadian Institutes of Health Research. Dr. Garg reported having no relevant financial disclosures for this study.

[email protected]

SAN DIEGO – Among patients undergoing cardiac bypass surgery, perioperative use of corticosteroids did not alter the risk of acute kidney injury, results from a large randomized trial showed.

“Worldwide, over 20 million cardiac surgeries are done each year, but 4 million are complicated by acute kidney injury, and 200,000 are complicated by severe kidney injury treated with dialysis,” Dr. Amit X. Garg said during a press briefing at the annual meeting of the American Society of Nephrology. “So certainly people would benefit from a therapy to prevent acute kidney injury (AKI) and improve the safety of surgery.”

Dr. Garg, a nephrologist at the London Health Sciences Centre in London, Ontario, Canada, noted that cardiopulmonary bypass initiates a systemic inflammatory response syndrome, “which activates complement, inflammatory cytokines, and other inflammatory mediators, which in turn increases endothelial permeability, organ damage, and increased morbidity and mortality, including acute kidney injury.” Researchers are interested in corticosteroids, “because they suppress this inflammatory response. In other settings, such as acute glomerulonephritis, we successfully use corticosteroids to treat acute inflammation in the kidney,” he said.

In a study known as the Steroids in caRdiac Surgery Trial (SIRS), researchers at 79 centers in 18 countries set out to investigate if methylprednisolone alters the risk of acute kidney injury in patients undergoing cardiac surgery with cardiopulmonary bypass. Between June 2007 and December 2013, 7,286 patients were randomized to intravenous methylprednisolone 250 mg at anesthetic induction and 250 mg at initiation of coronary bypass, or placebo.

AKI was defined as a 0.3 mg/dL increase or greater in postoperative serum creatinine concentration from the preoperative concentration within 14 days following surgery, or a 50% increase from the preoperative value within 14 days following surgery. Secondary outcomes included different stages of AKI and receipt of acute dialysis in the 30 days following surgery. Patients, caregivers, and researchers were blinded to the treatment allocation.

Of the 7,286 patients, 3,647 received methylprednisolone and 3,639 received placebo. The mean age of patients was 60 years, 60% were men, 26% were diabetic, and 25% of patients had combined CABG and valve surgery.

The SIRS Investigators reported that the risk of AKI was similar among patients who received methylprednisolone and those who received placebo (40.9% vs. 39.5%, respectively; relative risk 1.03). Results were similar across multiple categorical definitions of AKI, including AKI or death (41.5% vs 40.2%; RR 1.03); AKI stage of 2 or greater (9.9% vs 9.9%; RR 1.01); AKI stage of 3 or greater (4% vs. 4.5%; RR .89), and being on acute dialysis (2.6% vs. 2.4%; RR 1.08).

“There was no benefit of steroids on the risk of AKI in those with or without preoperative chronic kidney disease,” Dr. Garg said. “The result was also not different in the subpopulation of patients with AKI as defined by Kidney Disease Improving Global Outcomes.” Results from SIRS “would suggest that patients undergoing cardiac surgery with cardiopulmonary bypass should not use prophylactic steroids to prevent AKI. When we consider the side effect profile, the most clinically relevant outcomes, and apply the GRADE framework [the Grading of Recommendations Assessment, Development, and Evaluation] to the available evidence, we would recommend that steroids not be used in this way, with a grade 1B recommendation.”

The study was sponsored by the Population Health Research Institute in Hamilton, Ontario and the Canadian Institutes of Health Research. Dr. Garg reported having no relevant financial disclosures for this study.

[email protected]

Coronary stent implantation guided by intravascular ultrasound reduces the 1-year rate of major adverse cardiac events in patients who have long lesions, compared with standard angiography-guided stent implantation, Dr. Sung-Jin Hong reported at the American Heart Association annual scientific sessions, a presentation that was simultaneously published online Nov. 10 in JAMA.

Even though four meta-analyses have demonstrated the superiority of IVUS-guided implantation and recent guidelines recommend IVUS guidance for select patients to optimize results, “the effect of IVUS-guided drug-eluting stent implantation on clinical outcomes remains uncertain because of the limited number of properly powered randomized clinical trials,” said Dr. Hong of Sanggye Paik Hospital at Inje University and of Severance Cardiovascular Hospital at Yonsei University, both in Seoul, South Korea.

Dr. Hong and his associates performed a 4-year industry-sponsored randomized trial comparing the two techniques in 1,400 patients who had typical chest pain or evidence of myocardial ischemia and were eligible to receive an everolimus-eluting stent of 28 mm or more in length. The study participants were randomly assigned to undergo either IVUS-guided (700 patients) or angiography-guided (700 patients) stent implantation at 20 Korean medical centers and were followed up for 1 year. The mean patient age was 64 years, and 69% of the participants were men. The mean stent length of the targeted lesions was 39.3 mm.

The primary endpoint – a composite of major adverse cardiac events such as death, target-lesion-related MI, or ischemia-driven revascularization of the target lesion at 1 year – occurred in 2.9% of the IVUS group and 5.8% of the angiography group. This is a significant difference, with the IVUS group showing a 2.9% absolute reduction and a 48% relative reduction in the primary endpoint, the investigators said (JAMA 2015 Nov 10. doi: 10.1001/jama.2015.15454).

The superiority of IVUS-guided stent implantation was attributable primarily to a marked decrease in target-lesion revascularization in that group (2.5% of patients) compared with the angiography-guided group (5.0%). This in turn was likely due to the fact that adjunctive poststent balloon dilation was done more frequently in the IVUS group (76% vs 57%) and that the mean final balloon size was larger. Consequently, the minimum lumen diameter was greater in the IVUS-guided stent group than in the angiography-guided stent group.

“To our knowledge, [this] is the first demonstration of the clinical benefit of IVUS guidance in second-generation drug-eluting stent implantation in an adequately powered randomized clinical trial,” the investigators added.

Coronary stent implantation guided by intravascular ultrasound reduces the 1-year rate of major adverse cardiac events in patients who have long lesions, compared with standard angiography-guided stent implantation, Dr. Sung-Jin Hong reported at the American Heart Association annual scientific sessions, a presentation that was simultaneously published online Nov. 10 in JAMA.

Even though four meta-analyses have demonstrated the superiority of IVUS-guided implantation and recent guidelines recommend IVUS guidance for select patients to optimize results, “the effect of IVUS-guided drug-eluting stent implantation on clinical outcomes remains uncertain because of the limited number of properly powered randomized clinical trials,” said Dr. Hong of Sanggye Paik Hospital at Inje University and of Severance Cardiovascular Hospital at Yonsei University, both in Seoul, South Korea.

Dr. Hong and his associates performed a 4-year industry-sponsored randomized trial comparing the two techniques in 1,400 patients who had typical chest pain or evidence of myocardial ischemia and were eligible to receive an everolimus-eluting stent of 28 mm or more in length. The study participants were randomly assigned to undergo either IVUS-guided (700 patients) or angiography-guided (700 patients) stent implantation at 20 Korean medical centers and were followed up for 1 year. The mean patient age was 64 years, and 69% of the participants were men. The mean stent length of the targeted lesions was 39.3 mm.

The primary endpoint – a composite of major adverse cardiac events such as death, target-lesion-related MI, or ischemia-driven revascularization of the target lesion at 1 year – occurred in 2.9% of the IVUS group and 5.8% of the angiography group. This is a significant difference, with the IVUS group showing a 2.9% absolute reduction and a 48% relative reduction in the primary endpoint, the investigators said (JAMA 2015 Nov 10. doi: 10.1001/jama.2015.15454).

The superiority of IVUS-guided stent implantation was attributable primarily to a marked decrease in target-lesion revascularization in that group (2.5% of patients) compared with the angiography-guided group (5.0%). This in turn was likely due to the fact that adjunctive poststent balloon dilation was done more frequently in the IVUS group (76% vs 57%) and that the mean final balloon size was larger. Consequently, the minimum lumen diameter was greater in the IVUS-guided stent group than in the angiography-guided stent group.

“To our knowledge, [this] is the first demonstration of the clinical benefit of IVUS guidance in second-generation drug-eluting stent implantation in an adequately powered randomized clinical trial,” the investigators added.

Coronary stent implantation guided by intravascular ultrasound reduces the 1-year rate of major adverse cardiac events in patients who have long lesions, compared with standard angiography-guided stent implantation, Dr. Sung-Jin Hong reported at the American Heart Association annual scientific sessions, a presentation that was simultaneously published online Nov. 10 in JAMA.

Even though four meta-analyses have demonstrated the superiority of IVUS-guided implantation and recent guidelines recommend IVUS guidance for select patients to optimize results, “the effect of IVUS-guided drug-eluting stent implantation on clinical outcomes remains uncertain because of the limited number of properly powered randomized clinical trials,” said Dr. Hong of Sanggye Paik Hospital at Inje University and of Severance Cardiovascular Hospital at Yonsei University, both in Seoul, South Korea.

Dr. Hong and his associates performed a 4-year industry-sponsored randomized trial comparing the two techniques in 1,400 patients who had typical chest pain or evidence of myocardial ischemia and were eligible to receive an everolimus-eluting stent of 28 mm or more in length. The study participants were randomly assigned to undergo either IVUS-guided (700 patients) or angiography-guided (700 patients) stent implantation at 20 Korean medical centers and were followed up for 1 year. The mean patient age was 64 years, and 69% of the participants were men. The mean stent length of the targeted lesions was 39.3 mm.

The primary endpoint – a composite of major adverse cardiac events such as death, target-lesion-related MI, or ischemia-driven revascularization of the target lesion at 1 year – occurred in 2.9% of the IVUS group and 5.8% of the angiography group. This is a significant difference, with the IVUS group showing a 2.9% absolute reduction and a 48% relative reduction in the primary endpoint, the investigators said (JAMA 2015 Nov 10. doi: 10.1001/jama.2015.15454).

The superiority of IVUS-guided stent implantation was attributable primarily to a marked decrease in target-lesion revascularization in that group (2.5% of patients) compared with the angiography-guided group (5.0%). This in turn was likely due to the fact that adjunctive poststent balloon dilation was done more frequently in the IVUS group (76% vs 57%) and that the mean final balloon size was larger. Consequently, the minimum lumen diameter was greater in the IVUS-guided stent group than in the angiography-guided stent group.

“To our knowledge, [this] is the first demonstration of the clinical benefit of IVUS guidance in second-generation drug-eluting stent implantation in an adequately powered randomized clinical trial,” the investigators added.

ORLANDO – A leadless transcatheter pacemaker rivals conventional transvenous pacemakers in terms of pacing capture and major complications, according to data presented at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.

The prospective multicenter study involved 725 patients requiring ventricular pacing, of whom 719 were successful implanted with the leadless Micra Transcatheter Pacemaking System and followed for 6 months.

Of the 297 patients included in the primary efficacy analysis, 98.3% showed a 6-month pacing capture threshold of no greater than 2.0 V, with a mean pacing capture threshold at implantation of 0.63 V and 0.54 V at 6 months.

The leadless device also was associated with half the incidence of major complications, compared with data from a historical control cohort (4% vs. 7.4%; hazard ratio, 0.49; P = .001), as well as fewer hospitalizations and fewer system revisions due to complications.

“Complications that lead to death or that required invasive revision, termination of therapy, or hospitalization or extension of hospitalization occurred in 4% of the patients; this finding is in line with recent reports of transvenous systems and was significantly lower than the rate in the control group,” wrote Dr. Dwight Reynolds of the University of Oklahoma Health Sciences Center, Oklahoma City, and coauthors (N Engl J Med. Nov 9. doi: 10.1056/NEJMoa1511643).

The study was supported by Micra manufacturer Medtronic. Most authors reported personal fees, grants, and advisory board positions from private industry, including Medtronic. Two authors are Medtronic employees.

ORLANDO – A leadless transcatheter pacemaker rivals conventional transvenous pacemakers in terms of pacing capture and major complications, according to data presented at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.

The prospective multicenter study involved 725 patients requiring ventricular pacing, of whom 719 were successful implanted with the leadless Micra Transcatheter Pacemaking System and followed for 6 months.

Of the 297 patients included in the primary efficacy analysis, 98.3% showed a 6-month pacing capture threshold of no greater than 2.0 V, with a mean pacing capture threshold at implantation of 0.63 V and 0.54 V at 6 months.

The leadless device also was associated with half the incidence of major complications, compared with data from a historical control cohort (4% vs. 7.4%; hazard ratio, 0.49; P = .001), as well as fewer hospitalizations and fewer system revisions due to complications.

“Complications that lead to death or that required invasive revision, termination of therapy, or hospitalization or extension of hospitalization occurred in 4% of the patients; this finding is in line with recent reports of transvenous systems and was significantly lower than the rate in the control group,” wrote Dr. Dwight Reynolds of the University of Oklahoma Health Sciences Center, Oklahoma City, and coauthors (N Engl J Med. Nov 9. doi: 10.1056/NEJMoa1511643).

The study was supported by Micra manufacturer Medtronic. Most authors reported personal fees, grants, and advisory board positions from private industry, including Medtronic. Two authors are Medtronic employees.

ORLANDO – A leadless transcatheter pacemaker rivals conventional transvenous pacemakers in terms of pacing capture and major complications, according to data presented at the American Heart Association scientific sessions and published simultaneously in the New England Journal of Medicine.

The prospective multicenter study involved 725 patients requiring ventricular pacing, of whom 719 were successful implanted with the leadless Micra Transcatheter Pacemaking System and followed for 6 months.

Of the 297 patients included in the primary efficacy analysis, 98.3% showed a 6-month pacing capture threshold of no greater than 2.0 V, with a mean pacing capture threshold at implantation of 0.63 V and 0.54 V at 6 months.

The leadless device also was associated with half the incidence of major complications, compared with data from a historical control cohort (4% vs. 7.4%; hazard ratio, 0.49; P = .001), as well as fewer hospitalizations and fewer system revisions due to complications.

“Complications that lead to death or that required invasive revision, termination of therapy, or hospitalization or extension of hospitalization occurred in 4% of the patients; this finding is in line with recent reports of transvenous systems and was significantly lower than the rate in the control group,” wrote Dr. Dwight Reynolds of the University of Oklahoma Health Sciences Center, Oklahoma City, and coauthors (N Engl J Med. Nov 9. doi: 10.1056/NEJMoa1511643).

The study was supported by Micra manufacturer Medtronic. Most authors reported personal fees, grants, and advisory board positions from private industry, including Medtronic. Two authors are Medtronic employees.

Whether to operate on patients with severe aortic regurgitation (AR) before or after symptoms appear has been a point of controversy among cardiothoracic surgeons, but a recent study has found that patients who have early surgery may not fare any better for up to 10 years than those who opt for a more conservative “watchful waiting” course of care.

Investigators from Belgium reported results from an analysis of 160 patients in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1100-08). “In asymptomatic severe AR, delaying surgery until the onset of class I/IIa operative triggers is safe, supporting current guidelines,” said Dr. Christophe de Meester and colleagues at the Catholic University of Louvain and St. Luc University Clinic in Brussels.

The goal of the study was to evaluate long-term outcomes and incidence of cardiac complications in patients with severe AR who did not have any signs and symptoms that called for surgery, and who either had surgery early on or entered conservative management and eventually had an operation when signs and symptoms did appear.

The study found that close follow-up and monitoring of patients with severe AR was a cornerstone of successful conservative management. “We found that survival was similar between the two groups,” Dr. De Meester and coauthors said. “Better survival was nonetheless observed in conservatively managed patients with regular as opposed to no or a looser follow-up.”

The most recent European Society of Cardiology (ESC) guidelines and American Heart Association/American College of Cardiology guidelines state that symptomatic severe AR is a class I indication for surgery regardless of left ventricular (LV) systolic function.

However, Dr. De Meester and colleagues said, the timing of that surgery is not so clear-cut. Earlier studies have shown that surgery could be delayed for patients with minimal symptoms, but more recent evidence has suggested the opposite, according to the study. Two factors favor surgery before symptoms arise – poor aortic valve repair outcomes in patients with symptoms of heart failure and long-standing severe AR, which eventually leads to LV dysfunction.

Yet, the latest ESC guidelines have been “reluctant” to make a strong case for early surgery before symptoms of LV dysfunction appear, and the AHA/ACC guidelines call for surgery only when symptoms of LV dysfunction or LV dilatation develop, Dr. de Meester and his coauthors said.

In the past, the risks of aortic valve replacement were too high to consider early surgery, the study authors said. “However, with the advent of aortic valve repair, operative mortality and long-term outcomes have improved to such an extent that early surgery has become a plausible option for patients.”

But the risk of these patients developing symptoms for surgery was nonetheless low over 10 years, the study found: 7.4% for developing severe LV dilatation; 0.6% for becoming symptomatic; and 0.9% for developing LV dysfunction. Overall, the rate of adverse events in the study population was 9.9% at 10 years.

In the study, 69 patients were initially managed conservatively, 49 of whom were in the watchful waiting group that visited a cardiologist at least annually and another 20 considered an “irregular follow-up subgroup.” Among the watchful waiting group, 31 developed symptoms for surgery (only two declined surgery). Watchful waiting patients had five- and 10-year survival of 100% and 95%, respectively, compared with 90% and 79% among those who had irregular follow-up.

Overall, the conservatively managed group had outcomes better than or equal to the early surgery group. Ten-year cardiovascular survival was 96% in both groups, whereas event-free survival was 92% at 10 years in the conservatively managed group vs. 81% in the early surgery group.

The study was supported by the Belgium National Fund for Scientific Research. The authors had no conflicts to disclose.

Whether to operate on patients with severe aortic regurgitation (AR) before or after symptoms appear has been a point of controversy among cardiothoracic surgeons, but a recent study has found that patients who have early surgery may not fare any better for up to 10 years than those who opt for a more conservative “watchful waiting” course of care.

Investigators from Belgium reported results from an analysis of 160 patients in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1100-08). “In asymptomatic severe AR, delaying surgery until the onset of class I/IIa operative triggers is safe, supporting current guidelines,” said Dr. Christophe de Meester and colleagues at the Catholic University of Louvain and St. Luc University Clinic in Brussels.

The goal of the study was to evaluate long-term outcomes and incidence of cardiac complications in patients with severe AR who did not have any signs and symptoms that called for surgery, and who either had surgery early on or entered conservative management and eventually had an operation when signs and symptoms did appear.

The study found that close follow-up and monitoring of patients with severe AR was a cornerstone of successful conservative management. “We found that survival was similar between the two groups,” Dr. De Meester and coauthors said. “Better survival was nonetheless observed in conservatively managed patients with regular as opposed to no or a looser follow-up.”

The most recent European Society of Cardiology (ESC) guidelines and American Heart Association/American College of Cardiology guidelines state that symptomatic severe AR is a class I indication for surgery regardless of left ventricular (LV) systolic function.

However, Dr. De Meester and colleagues said, the timing of that surgery is not so clear-cut. Earlier studies have shown that surgery could be delayed for patients with minimal symptoms, but more recent evidence has suggested the opposite, according to the study. Two factors favor surgery before symptoms arise – poor aortic valve repair outcomes in patients with symptoms of heart failure and long-standing severe AR, which eventually leads to LV dysfunction.

Yet, the latest ESC guidelines have been “reluctant” to make a strong case for early surgery before symptoms of LV dysfunction appear, and the AHA/ACC guidelines call for surgery only when symptoms of LV dysfunction or LV dilatation develop, Dr. de Meester and his coauthors said.

In the past, the risks of aortic valve replacement were too high to consider early surgery, the study authors said. “However, with the advent of aortic valve repair, operative mortality and long-term outcomes have improved to such an extent that early surgery has become a plausible option for patients.”

But the risk of these patients developing symptoms for surgery was nonetheless low over 10 years, the study found: 7.4% for developing severe LV dilatation; 0.6% for becoming symptomatic; and 0.9% for developing LV dysfunction. Overall, the rate of adverse events in the study population was 9.9% at 10 years.

In the study, 69 patients were initially managed conservatively, 49 of whom were in the watchful waiting group that visited a cardiologist at least annually and another 20 considered an “irregular follow-up subgroup.” Among the watchful waiting group, 31 developed symptoms for surgery (only two declined surgery). Watchful waiting patients had five- and 10-year survival of 100% and 95%, respectively, compared with 90% and 79% among those who had irregular follow-up.

Overall, the conservatively managed group had outcomes better than or equal to the early surgery group. Ten-year cardiovascular survival was 96% in both groups, whereas event-free survival was 92% at 10 years in the conservatively managed group vs. 81% in the early surgery group.

The study was supported by the Belgium National Fund for Scientific Research. The authors had no conflicts to disclose.

Whether to operate on patients with severe aortic regurgitation (AR) before or after symptoms appear has been a point of controversy among cardiothoracic surgeons, but a recent study has found that patients who have early surgery may not fare any better for up to 10 years than those who opt for a more conservative “watchful waiting” course of care.

Investigators from Belgium reported results from an analysis of 160 patients in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1100-08). “In asymptomatic severe AR, delaying surgery until the onset of class I/IIa operative triggers is safe, supporting current guidelines,” said Dr. Christophe de Meester and colleagues at the Catholic University of Louvain and St. Luc University Clinic in Brussels.

The goal of the study was to evaluate long-term outcomes and incidence of cardiac complications in patients with severe AR who did not have any signs and symptoms that called for surgery, and who either had surgery early on or entered conservative management and eventually had an operation when signs and symptoms did appear.

The study found that close follow-up and monitoring of patients with severe AR was a cornerstone of successful conservative management. “We found that survival was similar between the two groups,” Dr. De Meester and coauthors said. “Better survival was nonetheless observed in conservatively managed patients with regular as opposed to no or a looser follow-up.”

The most recent European Society of Cardiology (ESC) guidelines and American Heart Association/American College of Cardiology guidelines state that symptomatic severe AR is a class I indication for surgery regardless of left ventricular (LV) systolic function.

However, Dr. De Meester and colleagues said, the timing of that surgery is not so clear-cut. Earlier studies have shown that surgery could be delayed for patients with minimal symptoms, but more recent evidence has suggested the opposite, according to the study. Two factors favor surgery before symptoms arise – poor aortic valve repair outcomes in patients with symptoms of heart failure and long-standing severe AR, which eventually leads to LV dysfunction.

Yet, the latest ESC guidelines have been “reluctant” to make a strong case for early surgery before symptoms of LV dysfunction appear, and the AHA/ACC guidelines call for surgery only when symptoms of LV dysfunction or LV dilatation develop, Dr. de Meester and his coauthors said.

In the past, the risks of aortic valve replacement were too high to consider early surgery, the study authors said. “However, with the advent of aortic valve repair, operative mortality and long-term outcomes have improved to such an extent that early surgery has become a plausible option for patients.”

But the risk of these patients developing symptoms for surgery was nonetheless low over 10 years, the study found: 7.4% for developing severe LV dilatation; 0.6% for becoming symptomatic; and 0.9% for developing LV dysfunction. Overall, the rate of adverse events in the study population was 9.9% at 10 years.

In the study, 69 patients were initially managed conservatively, 49 of whom were in the watchful waiting group that visited a cardiologist at least annually and another 20 considered an “irregular follow-up subgroup.” Among the watchful waiting group, 31 developed symptoms for surgery (only two declined surgery). Watchful waiting patients had five- and 10-year survival of 100% and 95%, respectively, compared with 90% and 79% among those who had irregular follow-up.

Overall, the conservatively managed group had outcomes better than or equal to the early surgery group. Ten-year cardiovascular survival was 96% in both groups, whereas event-free survival was 92% at 10 years in the conservatively managed group vs. 81% in the early surgery group.

The study was supported by the Belgium National Fund for Scientific Research. The authors had no conflicts to disclose.

Placement of a left ventricular assist device (LVAD) after a heart attack has been found to suppress certain cellular signaling pathways that protect coronary tissue, but at the same time LVAD placement seemed to help normalize other protective properties in areas of the heart closest to the infarcted region, investigators reported in a recent study.

The findings could have implications in determining the best method for unloading and other medical therapies in the aftermath of a heart attack, Dr. Keshava Rajagopal of the University of Texas, Houston, and associates reported in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1332-41).

To study the effect of LVAD on cardiac tissue, the investigators induced myocardial infarction in sheep and then placed the animals on LVAD support for 2 weeks. After 10 more weeks of observation, the investigators harvested and analyzed the myocardial specimens. The principal goal of the study was to investigate how heart attack and subsequent short-term mechanical support of the left ventricle can influence signaling controlled by the protein beta-arrestin.

They found that an infarction of myocardial tissue caused activation of the beta-arrestin protein that regulates cellular pathways that can benefit cardiac cells. At the same time, LVAD support inhibited beta-arrestin activation, specifically in regulating pathways of two cardioprotective proteins: Akt, also called protein kinase B (PKB), and, to a lesser extent, ERK-1 and -2.

They also found that MI resulted in regional activation of load-induced signaling of cardiac G protein-coupled receptor (GPCR) via G proteins.

“These studies demonstrate that small platform catheter-based LVAD support exerts suppressive effects on cardioprotective beta-arrestin–mediated signal transduction, while normalizing the signaling networks of G-alpha-q–coupled cardiac GPCRS in the MI-adjacent zone,” Dr. Rajagopal and colleagues said.

They acknowledged that further studies are needed to better understand the roles that specific GPCRs in beta-arrestin–regulated signaling play in left ventricle dysfunction after a heart attack and to help define the optimal timing for LVAD based on signaling and genetic markers along with standard LV functional endpoints.

The authors had no disclosures.

Placement of a left ventricular assist device (LVAD) after a heart attack has been found to suppress certain cellular signaling pathways that protect coronary tissue, but at the same time LVAD placement seemed to help normalize other protective properties in areas of the heart closest to the infarcted region, investigators reported in a recent study.

The findings could have implications in determining the best method for unloading and other medical therapies in the aftermath of a heart attack, Dr. Keshava Rajagopal of the University of Texas, Houston, and associates reported in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1332-41).

To study the effect of LVAD on cardiac tissue, the investigators induced myocardial infarction in sheep and then placed the animals on LVAD support for 2 weeks. After 10 more weeks of observation, the investigators harvested and analyzed the myocardial specimens. The principal goal of the study was to investigate how heart attack and subsequent short-term mechanical support of the left ventricle can influence signaling controlled by the protein beta-arrestin.

They found that an infarction of myocardial tissue caused activation of the beta-arrestin protein that regulates cellular pathways that can benefit cardiac cells. At the same time, LVAD support inhibited beta-arrestin activation, specifically in regulating pathways of two cardioprotective proteins: Akt, also called protein kinase B (PKB), and, to a lesser extent, ERK-1 and -2.

They also found that MI resulted in regional activation of load-induced signaling of cardiac G protein-coupled receptor (GPCR) via G proteins.

“These studies demonstrate that small platform catheter-based LVAD support exerts suppressive effects on cardioprotective beta-arrestin–mediated signal transduction, while normalizing the signaling networks of G-alpha-q–coupled cardiac GPCRS in the MI-adjacent zone,” Dr. Rajagopal and colleagues said.

They acknowledged that further studies are needed to better understand the roles that specific GPCRs in beta-arrestin–regulated signaling play in left ventricle dysfunction after a heart attack and to help define the optimal timing for LVAD based on signaling and genetic markers along with standard LV functional endpoints.

The authors had no disclosures.

Placement of a left ventricular assist device (LVAD) after a heart attack has been found to suppress certain cellular signaling pathways that protect coronary tissue, but at the same time LVAD placement seemed to help normalize other protective properties in areas of the heart closest to the infarcted region, investigators reported in a recent study.

The findings could have implications in determining the best method for unloading and other medical therapies in the aftermath of a heart attack, Dr. Keshava Rajagopal of the University of Texas, Houston, and associates reported in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1332-41).

To study the effect of LVAD on cardiac tissue, the investigators induced myocardial infarction in sheep and then placed the animals on LVAD support for 2 weeks. After 10 more weeks of observation, the investigators harvested and analyzed the myocardial specimens. The principal goal of the study was to investigate how heart attack and subsequent short-term mechanical support of the left ventricle can influence signaling controlled by the protein beta-arrestin.

They found that an infarction of myocardial tissue caused activation of the beta-arrestin protein that regulates cellular pathways that can benefit cardiac cells. At the same time, LVAD support inhibited beta-arrestin activation, specifically in regulating pathways of two cardioprotective proteins: Akt, also called protein kinase B (PKB), and, to a lesser extent, ERK-1 and -2.

They also found that MI resulted in regional activation of load-induced signaling of cardiac G protein-coupled receptor (GPCR) via G proteins.

“These studies demonstrate that small platform catheter-based LVAD support exerts suppressive effects on cardioprotective beta-arrestin–mediated signal transduction, while normalizing the signaling networks of G-alpha-q–coupled cardiac GPCRS in the MI-adjacent zone,” Dr. Rajagopal and colleagues said.

They acknowledged that further studies are needed to better understand the roles that specific GPCRs in beta-arrestin–regulated signaling play in left ventricle dysfunction after a heart attack and to help define the optimal timing for LVAD based on signaling and genetic markers along with standard LV functional endpoints.

The authors had no disclosures.

A hybrid coronary revascularization procedure that combines off-pump left internal mammary artery (LIMA) grafting with percutaneous coronary intervention (PCI) showed good results at 1 year after surgery, but nonetheless showed a rate of adverse events that may raise questions about the procedure.

In a study published in the November issue of the Journal of Thoracic and Cardiovascular Surgery, a team of investigators from Aarhus University Hospital in Denmark reported high rates of graft patency and low rates of death and stroke with the procedure 1 year after a series of 100 operations (J Thorac Cardiovasc Surg. 2015;150:1181-6).

Courtesy JTCVS

“The high left internal mammary artery graft patency rate and low risk of death and stroke at 1 year seem promising for the long-term outcome of this revascularization strategy,” said Dr. Ivy Susanne Modrau and colleagues.

The single-center study evaluated 1-year clinical and angiographic results of 100 consecutive trial patients with multivessel disease who had the hybrid procedure between October 2010 and February 2012. “The rationale of hybrid coronary revascularization is to achieve the survival benefits of the LIMA to LAD (left anterior descending artery) graft with reduced invasiveness to minimize postprocedural discomfort and morbidity, in particular the risk of stroke,” Dr. Modrau and colleagues said.

The study used the LIMA to LAD graft performed off-pump through a reversed J-hemisternotomy “We chose this technique because of its excellent exposure of the heart, technical ease, low risk of complicating chronic pain, and applicability in virtually all patients,” Dr. Modrau said. Eighty-nine patients had surgery prior to PCI and 11 had PCI prior to surgery.

The primary endpoint was rate of major adverse cardiac or cerebrovascular events (MACCE), the composite of all-cause death, stroke, myocardial infarction, and repeat revascularization by PCI or coronary artery bypass grafting at 1 year. Secondary endpoints included individual components and status of stent and graft patency on angiography.

Overall, 20 patients met the 1-year primary endpoint of MACCE. One patient died, one other had a stroke, and three had heart attacks. Sixteen patients had repeat revascularization procedures, eight performed during the index hospitalization. Graft patency was 98% after 1 year.

Dr. Modrau and coauthors noted the MACCE rate of 20% “was higher than expected,” and certainly higher than results in the SYNTAX study (17.8% in the PCI group and 12.4% in the coronary artery bypass grafting [CABG] group) (Euro. Intervention. 2015;10:e1-e6). One possible reason the Danish investigators cited for higher than expected MACCE rates was that they may be attributed to the learning curve involved with LIMA grafting and the use of early angiography possibly revealing “clinically silent LIMA graft dysfunction due to technical errors.”

The number of repeat revascularizations in the study was more in line with the SYNTAX study: 7% in the Aarhus University study and 6% in the SYNTAX CABG group. However, a meta-analysis of six studies with 1,190 patients reported 1-year repeat revascularization rates of 3.8% after a hybrid procedure and 1.4% after CABG (Am Heart J. 2014;167:585-92).

Ultimately, the safety and efficacy of the hybrid revascularization approach will require long-term follow-up data and head-to-head comparison with conventional CABG and PCI in clinical trials. “Meanwhile, LIMA patency, the cornerstone of surgical revascularization, may be used as a surrogate endpoint for long-term survival after HCR,” Dr. Modrau and coauthors said.

They reported having no disclosures.

A hybrid coronary revascularization procedure that combines off-pump left internal mammary artery (LIMA) grafting with percutaneous coronary intervention (PCI) showed good results at 1 year after surgery, but nonetheless showed a rate of adverse events that may raise questions about the procedure.

In a study published in the November issue of the Journal of Thoracic and Cardiovascular Surgery, a team of investigators from Aarhus University Hospital in Denmark reported high rates of graft patency and low rates of death and stroke with the procedure 1 year after a series of 100 operations (J Thorac Cardiovasc Surg. 2015;150:1181-6).

Courtesy JTCVS

“The high left internal mammary artery graft patency rate and low risk of death and stroke at 1 year seem promising for the long-term outcome of this revascularization strategy,” said Dr. Ivy Susanne Modrau and colleagues.

The single-center study evaluated 1-year clinical and angiographic results of 100 consecutive trial patients with multivessel disease who had the hybrid procedure between October 2010 and February 2012. “The rationale of hybrid coronary revascularization is to achieve the survival benefits of the LIMA to LAD (left anterior descending artery) graft with reduced invasiveness to minimize postprocedural discomfort and morbidity, in particular the risk of stroke,” Dr. Modrau and colleagues said.

The study used the LIMA to LAD graft performed off-pump through a reversed J-hemisternotomy “We chose this technique because of its excellent exposure of the heart, technical ease, low risk of complicating chronic pain, and applicability in virtually all patients,” Dr. Modrau said. Eighty-nine patients had surgery prior to PCI and 11 had PCI prior to surgery.

The primary endpoint was rate of major adverse cardiac or cerebrovascular events (MACCE), the composite of all-cause death, stroke, myocardial infarction, and repeat revascularization by PCI or coronary artery bypass grafting at 1 year. Secondary endpoints included individual components and status of stent and graft patency on angiography.

Overall, 20 patients met the 1-year primary endpoint of MACCE. One patient died, one other had a stroke, and three had heart attacks. Sixteen patients had repeat revascularization procedures, eight performed during the index hospitalization. Graft patency was 98% after 1 year.

Dr. Modrau and coauthors noted the MACCE rate of 20% “was higher than expected,” and certainly higher than results in the SYNTAX study (17.8% in the PCI group and 12.4% in the coronary artery bypass grafting [CABG] group) (Euro. Intervention. 2015;10:e1-e6). One possible reason the Danish investigators cited for higher than expected MACCE rates was that they may be attributed to the learning curve involved with LIMA grafting and the use of early angiography possibly revealing “clinically silent LIMA graft dysfunction due to technical errors.”

The number of repeat revascularizations in the study was more in line with the SYNTAX study: 7% in the Aarhus University study and 6% in the SYNTAX CABG group. However, a meta-analysis of six studies with 1,190 patients reported 1-year repeat revascularization rates of 3.8% after a hybrid procedure and 1.4% after CABG (Am Heart J. 2014;167:585-92).

Ultimately, the safety and efficacy of the hybrid revascularization approach will require long-term follow-up data and head-to-head comparison with conventional CABG and PCI in clinical trials. “Meanwhile, LIMA patency, the cornerstone of surgical revascularization, may be used as a surrogate endpoint for long-term survival after HCR,” Dr. Modrau and coauthors said.

They reported having no disclosures.

A hybrid coronary revascularization procedure that combines off-pump left internal mammary artery (LIMA) grafting with percutaneous coronary intervention (PCI) showed good results at 1 year after surgery, but nonetheless showed a rate of adverse events that may raise questions about the procedure.

In a study published in the November issue of the Journal of Thoracic and Cardiovascular Surgery, a team of investigators from Aarhus University Hospital in Denmark reported high rates of graft patency and low rates of death and stroke with the procedure 1 year after a series of 100 operations (J Thorac Cardiovasc Surg. 2015;150:1181-6).

Courtesy JTCVS

“The high left internal mammary artery graft patency rate and low risk of death and stroke at 1 year seem promising for the long-term outcome of this revascularization strategy,” said Dr. Ivy Susanne Modrau and colleagues.

The single-center study evaluated 1-year clinical and angiographic results of 100 consecutive trial patients with multivessel disease who had the hybrid procedure between October 2010 and February 2012. “The rationale of hybrid coronary revascularization is to achieve the survival benefits of the LIMA to LAD (left anterior descending artery) graft with reduced invasiveness to minimize postprocedural discomfort and morbidity, in particular the risk of stroke,” Dr. Modrau and colleagues said.

The study used the LIMA to LAD graft performed off-pump through a reversed J-hemisternotomy “We chose this technique because of its excellent exposure of the heart, technical ease, low risk of complicating chronic pain, and applicability in virtually all patients,” Dr. Modrau said. Eighty-nine patients had surgery prior to PCI and 11 had PCI prior to surgery.

The primary endpoint was rate of major adverse cardiac or cerebrovascular events (MACCE), the composite of all-cause death, stroke, myocardial infarction, and repeat revascularization by PCI or coronary artery bypass grafting at 1 year. Secondary endpoints included individual components and status of stent and graft patency on angiography.

Overall, 20 patients met the 1-year primary endpoint of MACCE. One patient died, one other had a stroke, and three had heart attacks. Sixteen patients had repeat revascularization procedures, eight performed during the index hospitalization. Graft patency was 98% after 1 year.

Dr. Modrau and coauthors noted the MACCE rate of 20% “was higher than expected,” and certainly higher than results in the SYNTAX study (17.8% in the PCI group and 12.4% in the coronary artery bypass grafting [CABG] group) (Euro. Intervention. 2015;10:e1-e6). One possible reason the Danish investigators cited for higher than expected MACCE rates was that they may be attributed to the learning curve involved with LIMA grafting and the use of early angiography possibly revealing “clinically silent LIMA graft dysfunction due to technical errors.”

The number of repeat revascularizations in the study was more in line with the SYNTAX study: 7% in the Aarhus University study and 6% in the SYNTAX CABG group. However, a meta-analysis of six studies with 1,190 patients reported 1-year repeat revascularization rates of 3.8% after a hybrid procedure and 1.4% after CABG (Am Heart J. 2014;167:585-92).

Ultimately, the safety and efficacy of the hybrid revascularization approach will require long-term follow-up data and head-to-head comparison with conventional CABG and PCI in clinical trials. “Meanwhile, LIMA patency, the cornerstone of surgical revascularization, may be used as a surrogate endpoint for long-term survival after HCR,” Dr. Modrau and coauthors said.

They reported having no disclosures.

SAN FRANCISCO – The reversible direct thrombin inhibitor bivalirudin, compared with unfractionated heparin, did not reduce the rate of major bleeding at 48 hours after transcatheter aortic valve replacement, in the randomized, open label, phase IIIb BRAVO 3 trial.

Bivalirudin, which has a half-life of 25 minutes, has been shown to reduce major bleeding in the setting of percutaneous coronary intervention when compared with other regimens, but its safety and efficacy as compared with that of unfractionated heparin was unknown. In BRAVO 3 (The effect of BivaliRudin on Aortic Valve Intervention Outcomes trial), the rate of major bleeding at 48 hours, defined as Bleeding Academic Research Consortium (BARC) 3b or greater, was 6.9% in 404 patients treated with bivalirudin vs. 9.0% in 398 patients treated with heparin (relative risk, 0.77), Dr. Thierry Lefevre reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

Further, the rate of net adverse clinical outcomes (NACE), including all-cause mortality, myocardial infarction, stroke, and major bleeding at up to 30 days was 14.4% in the bivalirudin group vs. 16.1% in the heparin group (relative risk, 0.89), Dr. Lefevre of Institut Hospitalier Jacques Cartier, Massy, France, said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

The differences on both measures failed to meet statistical significance. With respect to bleeding at 48 hours, bivalirudin did not meet superiority, and with respect to cardiovascular events at 30 days, the prespecified noninferiority hypothesis was met.

No difference was seen between the groups for secondary endpoints, including bleeding defined according to various other bleeding scales and other BARC types.

The findings were published simultaneously in the Journal of the American College of Cardiology (J Am Coll Cardiol. 2015;Oct 15. doi: 10.1016/j.jacc.2015.10.003).

Heparin should remain the standard of care, especially given its lower cost compared to the cost of bivalirudin, Dr. Lefevre said.

However, Dr. Lefevre noted, major bleeding remains an important concern in transcatheter aortic valve replacement (TAVR), and “bivalirudin may be used as an alternative to heparin during TAVR in patients who cannot be treated with UFH.”

BRAVO III participants were adults with aortic stenosis who were at high surgical risk and who were scheduled for TAVR via transfemoral access. They were enrolled at 31 centers in seven countries throughout Europe and North America.

Those randomized to the bivalirudin group received an initial bolus of 0.75 mg/kg followed by a continuous infusion at a rate of 1.75 mg/kg per hour in those with an estimated glomerular filtration rate (eGFR) of 60 mL/min or greater, 1.4 mg/kg per hour in those with eGFR of 30-59 mL/min, and 1.0 mg/kg per hour in those with eGFR lower than 30 mL/min.

Heparin dosing and administration included a recommended target activated clotting time of greater than 25 seconds. Protamine was used for reversal at the end of the procedure based on standard local institution practice.

Session moderator Dr. Ajay J. Kirtane said that “one of the reasons this trial is exciting is that there has been a hypothesis that bivalirudin could reduce bleeding compared to heparin alone in PCI patients. While this is a much bigger access site, you don’t necessarily see these trends. On the other hand, when you have a bigger access site there is potential for increased signal, but this study is still somewhat underpowered.”

The Medicines Company provided funding for the BRAVO 3 trial to the Icahn School of Medicine at Mount Sinai, New York. Dr. Lefevre disclosed ties with Boston Scientific, Directflow, Edwards, Symetis and Medtronic.

[email protected]

SAN FRANCISCO – The reversible direct thrombin inhibitor bivalirudin, compared with unfractionated heparin, did not reduce the rate of major bleeding at 48 hours after transcatheter aortic valve replacement, in the randomized, open label, phase IIIb BRAVO 3 trial.

Bivalirudin, which has a half-life of 25 minutes, has been shown to reduce major bleeding in the setting of percutaneous coronary intervention when compared with other regimens, but its safety and efficacy as compared with that of unfractionated heparin was unknown. In BRAVO 3 (The effect of BivaliRudin on Aortic Valve Intervention Outcomes trial), the rate of major bleeding at 48 hours, defined as Bleeding Academic Research Consortium (BARC) 3b or greater, was 6.9% in 404 patients treated with bivalirudin vs. 9.0% in 398 patients treated with heparin (relative risk, 0.77), Dr. Thierry Lefevre reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

Further, the rate of net adverse clinical outcomes (NACE), including all-cause mortality, myocardial infarction, stroke, and major bleeding at up to 30 days was 14.4% in the bivalirudin group vs. 16.1% in the heparin group (relative risk, 0.89), Dr. Lefevre of Institut Hospitalier Jacques Cartier, Massy, France, said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

The differences on both measures failed to meet statistical significance. With respect to bleeding at 48 hours, bivalirudin did not meet superiority, and with respect to cardiovascular events at 30 days, the prespecified noninferiority hypothesis was met.

No difference was seen between the groups for secondary endpoints, including bleeding defined according to various other bleeding scales and other BARC types.

The findings were published simultaneously in the Journal of the American College of Cardiology (J Am Coll Cardiol. 2015;Oct 15. doi: 10.1016/j.jacc.2015.10.003).

Heparin should remain the standard of care, especially given its lower cost compared to the cost of bivalirudin, Dr. Lefevre said.

However, Dr. Lefevre noted, major bleeding remains an important concern in transcatheter aortic valve replacement (TAVR), and “bivalirudin may be used as an alternative to heparin during TAVR in patients who cannot be treated with UFH.”

BRAVO III participants were adults with aortic stenosis who were at high surgical risk and who were scheduled for TAVR via transfemoral access. They were enrolled at 31 centers in seven countries throughout Europe and North America.

Those randomized to the bivalirudin group received an initial bolus of 0.75 mg/kg followed by a continuous infusion at a rate of 1.75 mg/kg per hour in those with an estimated glomerular filtration rate (eGFR) of 60 mL/min or greater, 1.4 mg/kg per hour in those with eGFR of 30-59 mL/min, and 1.0 mg/kg per hour in those with eGFR lower than 30 mL/min.

Heparin dosing and administration included a recommended target activated clotting time of greater than 25 seconds. Protamine was used for reversal at the end of the procedure based on standard local institution practice.

Session moderator Dr. Ajay J. Kirtane said that “one of the reasons this trial is exciting is that there has been a hypothesis that bivalirudin could reduce bleeding compared to heparin alone in PCI patients. While this is a much bigger access site, you don’t necessarily see these trends. On the other hand, when you have a bigger access site there is potential for increased signal, but this study is still somewhat underpowered.”

The Medicines Company provided funding for the BRAVO 3 trial to the Icahn School of Medicine at Mount Sinai, New York. Dr. Lefevre disclosed ties with Boston Scientific, Directflow, Edwards, Symetis and Medtronic.

[email protected]

SAN FRANCISCO – The reversible direct thrombin inhibitor bivalirudin, compared with unfractionated heparin, did not reduce the rate of major bleeding at 48 hours after transcatheter aortic valve replacement, in the randomized, open label, phase IIIb BRAVO 3 trial.

Bivalirudin, which has a half-life of 25 minutes, has been shown to reduce major bleeding in the setting of percutaneous coronary intervention when compared with other regimens, but its safety and efficacy as compared with that of unfractionated heparin was unknown. In BRAVO 3 (The effect of BivaliRudin on Aortic Valve Intervention Outcomes trial), the rate of major bleeding at 48 hours, defined as Bleeding Academic Research Consortium (BARC) 3b or greater, was 6.9% in 404 patients treated with bivalirudin vs. 9.0% in 398 patients treated with heparin (relative risk, 0.77), Dr. Thierry Lefevre reported at the Transcatheter Cardiovascular Therapeutics annual meeting.

Further, the rate of net adverse clinical outcomes (NACE), including all-cause mortality, myocardial infarction, stroke, and major bleeding at up to 30 days was 14.4% in the bivalirudin group vs. 16.1% in the heparin group (relative risk, 0.89), Dr. Lefevre of Institut Hospitalier Jacques Cartier, Massy, France, said at the meeting, which was sponsored by the Cardiovascular Research Foundation.

The differences on both measures failed to meet statistical significance. With respect to bleeding at 48 hours, bivalirudin did not meet superiority, and with respect to cardiovascular events at 30 days, the prespecified noninferiority hypothesis was met.

No difference was seen between the groups for secondary endpoints, including bleeding defined according to various other bleeding scales and other BARC types.

The findings were published simultaneously in the Journal of the American College of Cardiology (J Am Coll Cardiol. 2015;Oct 15. doi: 10.1016/j.jacc.2015.10.003).

Heparin should remain the standard of care, especially given its lower cost compared to the cost of bivalirudin, Dr. Lefevre said.

However, Dr. Lefevre noted, major bleeding remains an important concern in transcatheter aortic valve replacement (TAVR), and “bivalirudin may be used as an alternative to heparin during TAVR in patients who cannot be treated with UFH.”

BRAVO III participants were adults with aortic stenosis who were at high surgical risk and who were scheduled for TAVR via transfemoral access. They were enrolled at 31 centers in seven countries throughout Europe and North America.

Those randomized to the bivalirudin group received an initial bolus of 0.75 mg/kg followed by a continuous infusion at a rate of 1.75 mg/kg per hour in those with an estimated glomerular filtration rate (eGFR) of 60 mL/min or greater, 1.4 mg/kg per hour in those with eGFR of 30-59 mL/min, and 1.0 mg/kg per hour in those with eGFR lower than 30 mL/min.

Heparin dosing and administration included a recommended target activated clotting time of greater than 25 seconds. Protamine was used for reversal at the end of the procedure based on standard local institution practice.

Session moderator Dr. Ajay J. Kirtane said that “one of the reasons this trial is exciting is that there has been a hypothesis that bivalirudin could reduce bleeding compared to heparin alone in PCI patients. While this is a much bigger access site, you don’t necessarily see these trends. On the other hand, when you have a bigger access site there is potential for increased signal, but this study is still somewhat underpowered.”

The Medicines Company provided funding for the BRAVO 3 trial to the Icahn School of Medicine at Mount Sinai, New York. Dr. Lefevre disclosed ties with Boston Scientific, Directflow, Edwards, Symetis and Medtronic.

[email protected]

SAN FRANCISCO - Early valve replacement may be in the best interest of asymptomatic patients with severe aortic stenosis, possibly halving their 5-year risk of death, based on data from the CURRENT AS registry study.

Compared to watchful waiting, early surgical intervention also reduced by 81% the risk of hospitalization for heart failure, Dr. Tomohiko Taniguchi said at the Transcatheter Cardiovascular Therapeutics annual meeting. The study was simultaneously published in the Journal of the American College of Cardiology (Am Coll Cardiol. 2015. doi: 10.1016/j.jacc.2015.10.001).

Observation has been the byword for asymptomatic patients with severe aortic stenosis (AS). The American College of Cardiology recommends a conservative approach to the asymptomatic AS patient, but acknowledges the disorder inevitably progresses in nearly all patients. In the ACC’s 2014 treatment guidelines, survival during the asymptomatic phase is similar to that of age-matched controls when patients are carefully followed.

But the CURRENT AS registry results suggest that “the long-term outcome of asymptomatic patients with severe aortic stenosis was dismal when they were managed conservatively in real clinical practice,” Dr. Taniguchi said during a press briefing at the meeting, which was sponsored by the Cardiovascular Research Foundation.

“If you’re watching and waiting, and you wait for sudden death, then that is a problem,” said Dr. Ajay J. Kirtane, who moderated the briefing. Early intervention “potentially changes the game because we do have a less-invasive procedure we can offer – transcatheter aortic valve replacement (AVR),” said Dr. Kirtane of New York-Presbyterian Hospital.

In the CURRENT AS study, severe AS was considered a peak aortic jet velocity over 4.0 m/s, or a mean aortic pressure gradient greater than 40 mm Hg, or an aortic valve area less than 1.0 cm². The registry includes 3,815 patients; Dr. Taniguchi of Kyoto University reported outcomes for a propensity-score matched cohort of 582 patients, 291 in the initial AVR group and 291 in the conservatively managed group. There was no treatment randomization; treatment decisions were made at the clinical level.

Patients in the matched cohort were in their early 70s; in 80%, the AS etiology was degenerative. The mean aortic pressure gradient was 54 mm Hg in the early intervention group and 45 mm Hg in the watchful waiting group. In 79% of the early intervention group and in 54% of the watchful waiting group, the mean aortic pressure gradient was below 40 mm Hg.

Among the patients who underwent AVR despite being asymptomatic, most (63%) had at least one surgical indication, including severe AS (41%), left ventricular dysfunction (7%), rapid hemodynamic progression (11%), or active infective endocarditis (0.3%). Other cardiac surgery indications were present in 8%. Many of the conservatively managed patients (41%) did eventually require AVR, Dr. Taniguchi noted.

By the end of the 5-year follow up period, 26% of the conservative therapy group and 15% of the early AVR group had died – a significant difference (hazard ratio, 0.64; P = .02).

The coprimary endpoint of heart failure hospitalization was also significantly more common among the conservatively treated group (19.9% vs. 3.8%; HR, 0.19; P less than .001).

The early intervention group also did significantly better on several secondary clinical outcomes, including cardiovascular death (10% vs. 18.6%), aortic valve-related death (5.3% vs. 13.5%), sudden death (3.6% vs. 5.8%), and emerging symptoms (3.2% vs. 46.3%).

Dr. Taniguchi had no financial disclosures. The study was sponsored by Kyoto University.

[email protected]

SAN FRANCISCO - Early valve replacement may be in the best interest of asymptomatic patients with severe aortic stenosis, possibly halving their 5-year risk of death, based on data from the CURRENT AS registry study.

Compared to watchful waiting, early surgical intervention also reduced by 81% the risk of hospitalization for heart failure, Dr. Tomohiko Taniguchi said at the Transcatheter Cardiovascular Therapeutics annual meeting. The study was simultaneously published in the Journal of the American College of Cardiology (Am Coll Cardiol. 2015. doi: 10.1016/j.jacc.2015.10.001).

Observation has been the byword for asymptomatic patients with severe aortic stenosis (AS). The American College of Cardiology recommends a conservative approach to the asymptomatic AS patient, but acknowledges the disorder inevitably progresses in nearly all patients. In the ACC’s 2014 treatment guidelines, survival during the asymptomatic phase is similar to that of age-matched controls when patients are carefully followed.

But the CURRENT AS registry results suggest that “the long-term outcome of asymptomatic patients with severe aortic stenosis was dismal when they were managed conservatively in real clinical practice,” Dr. Taniguchi said during a press briefing at the meeting, which was sponsored by the Cardiovascular Research Foundation.

“If you’re watching and waiting, and you wait for sudden death, then that is a problem,” said Dr. Ajay J. Kirtane, who moderated the briefing. Early intervention “potentially changes the game because we do have a less-invasive procedure we can offer – transcatheter aortic valve replacement (AVR),” said Dr. Kirtane of New York-Presbyterian Hospital.

In the CURRENT AS study, severe AS was considered a peak aortic jet velocity over 4.0 m/s, or a mean aortic pressure gradient greater than 40 mm Hg, or an aortic valve area less than 1.0 cm². The registry includes 3,815 patients; Dr. Taniguchi of Kyoto University reported outcomes for a propensity-score matched cohort of 582 patients, 291 in the initial AVR group and 291 in the conservatively managed group. There was no treatment randomization; treatment decisions were made at the clinical level.

Patients in the matched cohort were in their early 70s; in 80%, the AS etiology was degenerative. The mean aortic pressure gradient was 54 mm Hg in the early intervention group and 45 mm Hg in the watchful waiting group. In 79% of the early intervention group and in 54% of the watchful waiting group, the mean aortic pressure gradient was below 40 mm Hg.

Among the patients who underwent AVR despite being asymptomatic, most (63%) had at least one surgical indication, including severe AS (41%), left ventricular dysfunction (7%), rapid hemodynamic progression (11%), or active infective endocarditis (0.3%). Other cardiac surgery indications were present in 8%. Many of the conservatively managed patients (41%) did eventually require AVR, Dr. Taniguchi noted.

By the end of the 5-year follow up period, 26% of the conservative therapy group and 15% of the early AVR group had died – a significant difference (hazard ratio, 0.64; P = .02).

The coprimary endpoint of heart failure hospitalization was also significantly more common among the conservatively treated group (19.9% vs. 3.8%; HR, 0.19; P less than .001).

The early intervention group also did significantly better on several secondary clinical outcomes, including cardiovascular death (10% vs. 18.6%), aortic valve-related death (5.3% vs. 13.5%), sudden death (3.6% vs. 5.8%), and emerging symptoms (3.2% vs. 46.3%).

Dr. Taniguchi had no financial disclosures. The study was sponsored by Kyoto University.

[email protected]

SAN FRANCISCO - Early valve replacement may be in the best interest of asymptomatic patients with severe aortic stenosis, possibly halving their 5-year risk of death, based on data from the CURRENT AS registry study.

Compared to watchful waiting, early surgical intervention also reduced by 81% the risk of hospitalization for heart failure, Dr. Tomohiko Taniguchi said at the Transcatheter Cardiovascular Therapeutics annual meeting. The study was simultaneously published in the Journal of the American College of Cardiology (Am Coll Cardiol. 2015. doi: 10.1016/j.jacc.2015.10.001).

Observation has been the byword for asymptomatic patients with severe aortic stenosis (AS). The American College of Cardiology recommends a conservative approach to the asymptomatic AS patient, but acknowledges the disorder inevitably progresses in nearly all patients. In the ACC’s 2014 treatment guidelines, survival during the asymptomatic phase is similar to that of age-matched controls when patients are carefully followed.

But the CURRENT AS registry results suggest that “the long-term outcome of asymptomatic patients with severe aortic stenosis was dismal when they were managed conservatively in real clinical practice,” Dr. Taniguchi said during a press briefing at the meeting, which was sponsored by the Cardiovascular Research Foundation.

“If you’re watching and waiting, and you wait for sudden death, then that is a problem,” said Dr. Ajay J. Kirtane, who moderated the briefing. Early intervention “potentially changes the game because we do have a less-invasive procedure we can offer – transcatheter aortic valve replacement (AVR),” said Dr. Kirtane of New York-Presbyterian Hospital.

In the CURRENT AS study, severe AS was considered a peak aortic jet velocity over 4.0 m/s, or a mean aortic pressure gradient greater than 40 mm Hg, or an aortic valve area less than 1.0 cm². The registry includes 3,815 patients; Dr. Taniguchi of Kyoto University reported outcomes for a propensity-score matched cohort of 582 patients, 291 in the initial AVR group and 291 in the conservatively managed group. There was no treatment randomization; treatment decisions were made at the clinical level.

Patients in the matched cohort were in their early 70s; in 80%, the AS etiology was degenerative. The mean aortic pressure gradient was 54 mm Hg in the early intervention group and 45 mm Hg in the watchful waiting group. In 79% of the early intervention group and in 54% of the watchful waiting group, the mean aortic pressure gradient was below 40 mm Hg.

Among the patients who underwent AVR despite being asymptomatic, most (63%) had at least one surgical indication, including severe AS (41%), left ventricular dysfunction (7%), rapid hemodynamic progression (11%), or active infective endocarditis (0.3%). Other cardiac surgery indications were present in 8%. Many of the conservatively managed patients (41%) did eventually require AVR, Dr. Taniguchi noted.

By the end of the 5-year follow up period, 26% of the conservative therapy group and 15% of the early AVR group had died – a significant difference (hazard ratio, 0.64; P = .02).

The coprimary endpoint of heart failure hospitalization was also significantly more common among the conservatively treated group (19.9% vs. 3.8%; HR, 0.19; P less than .001).

The early intervention group also did significantly better on several secondary clinical outcomes, including cardiovascular death (10% vs. 18.6%), aortic valve-related death (5.3% vs. 13.5%), sudden death (3.6% vs. 5.8%), and emerging symptoms (3.2% vs. 46.3%).

Dr. Taniguchi had no financial disclosures. The study was sponsored by Kyoto University.

[email protected]