EuroPCR 2014

PARIS – Bioabsorbable vascular scaffolds have caught on in Europe and elsewhere in the world as an alternative to conventional metal stents for percutaneous coronary interventions in a wide spectrum of patient types.

By May 2014, more than 50,000 bioabsorbable vascular scaffolds (BVS) of the first brand to enter the European market – the Absorb stent made by Abbott Vascular – had gone into patients since the first placement in 2007, with the vast majority placed since this scaffold entered the European market in September 2012. Use of BVS in the United States remains investigational, while in the 20-plus months since BVS first became available in Europe other brands of BVS also have entered that market.

©wildpixel/iStockphoto.com

Despite growing BVS use in Europe, as well as in Asia and Central and South America, where they are also available, large-scale data on the consequences, especially long-term consequences, of BVS placement are mostly lacking, particularly data on how BVS perform when directly compared with drug-eluting metallic stents.

"Today we have uncontrolled dissemination of the technology without comparative data," Dr. Patrick W. Serruys, a pioneer in using BVS, said during a session at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

"We need evidence to know exactly what to do" with BVS, which patients to use them in, and when they are preferable to metallic stents, said Dr. Serruys, an interventional cardiologist and professor of medicine at the Thoraxcenter of Erasmus University in Rotterdam, the Netherlands.

"In the 7 years I’ve used them, in patients with 5-year follow-up, there have been no negative signals," he said in an interview, discussing his part of the sizeable anecdotal experience that BVS are safe and effective.

Several large trials comparing BVS with metal stents are in progress, including U.S. pivotal trials, but until these results are out, all that interventionalists have to gauge BVS performance are results from registries and uncontrolled trials. Given that limitation, so far the data look uniformly excellent.

"It is clear that emerging data from real-world, expanded-use registries suggest that use of the Absorb BVS is feasible and safe in a variety of patients, from low to high risk, and from simple to complex lesions," said Dr. Gregg W. Stone in a talk at the meeting. "But attention to procedural detail and technique is essential to optimize the outcomes. BVS are a little more complicated than metallic drug-eluting stents," said Dr. Stone, professor and director of cardiovascular research and education at Columbia University in New York.

"Data from large, randomized controlled trials are necessary to demonstrate whether BVS truly improve outcomes compared with best-in-class metallic stents. We are still early in the technology," he said. Dr. Stone is a lead investigator for one of the large U.S. randomized trials comparing the Absorb BVS to the current standard for percutaneous coronary interventions, a second-generation drug-eluting metallic stent.

Hints of what BVS may deliver

Hints of some of the potential benefits that BVS might provide appeared in results from a post-hoc, across-studies analysis that Dr. Stone presented in his talk. He compared the incidence of angina during the first year following PCI in 287 patients from the Absorb EXTEND study and 602 patients who received coronary stenting with the Xience second-generation everolimus-eluting metallic stent in the SPIRIT IV trial. The analysis matched patients in the Absorb arm with those in the Xience arm by propensity scoring.

The 1-year angina rates were 28% for the patients who received a metallic stent and 16% for those who received an absorbable scaffold, a 12% absolute difference, with a hazard ratio showing a 47% relative reduction in angina in patients who received the BVS, Dr. Stone reported. "There are a variety of mechanisms" by which BVS might reduce the rate of angina compared with metallic stents, including restoration of cyclic pulsatility in the treated arteries and improved vasomotion, he said.

The two outstanding clinical issues that dog PCI with second-generation drug-eluting metallic stents are the accrual of "very late" adverse events and the slow return of angina, with an average rate of target lesion failure with second-generation stents of about 1.8% year that continues out for at least 5 years, he said. "Can BVS flatten out the ongoing event rate" and improve measures like recurrent angina? Dr. Stone asked.

In another cross-study comparison, Dr. Serruys cited a recent, still unpublished analysis on which he collaborated that compared the 1-year outcomes of 102 patients with diabetes who received a BVS and 172 patients with diabetes who received a second-generation drug-eluting metallic stent. The 12-month cumulative rate of cardiovascular death, myocardial infarction, or ischemia-driven target lesion revascularization was 34.9% in the BVS recipients and 6.4% in patients who received state-of-the-art drug-eluting stents.

The working hypothesis behind BVS is that, by dissolving during a period of 12-24 months, the scaffold provides temporary bracing against restenosis but then disappears, allowing improved endovascular healing. During a separate session at EuroPCR, Dr. Charles A. Simonton, an interventional cardiologist and chief medical officer for Abbott Vascular, described the hypothesized impact that bioabsorbable coronary stents might have.

"Our vision is to convert interventional cardiology from mechanically oriented, plumbing-type interventions where you do mechanical things to open arteries" to a focus on tissue regeneration. "What we see when scaffolds resorb is that, at 3-5 years, the arteries look very different from what we see with a metal stent. The vessels show a highly functional neointimal layer that is functioning smooth muscle cells that protect against rupture in underlying plaque," he said.

Having BVS will allow interventional cardiologists to "transition from being mechanical plumbers to really being medical doctors. Not just opening lesions but putting in a treatment that can improve patients long term," Dr. Simonton said, presenting his best-case prediction of what BVS might achieve. "We need to generate a lot of data to make sure this is real," he added, in something of an understatement.

"There is late lumen enlargement with BVS. That is a clear fact," said Dr. Serruys.

The BVS experience

With data from studies that directly compared BVS and metallic stents still a few years off, the only indications of BVS performance now available come from either single- or multicenter registries. The thrust of much of these data presented at EuroPCR was that BVS have performed well as interventionalists have moved in the months since BVS became available for routine use to placing them in sicker patients and in patients with more complex coronary lesions.

Mitchel L. Zoler/Frontline Medical News

The largest registry is ABSORB First, a voluntary-reporting registry that began in January 2013 and involves about 90 centers in countries where Absorb is commercially available in Europe, Asia, New Zealand, and Columbia. Dr. Eric Eeckhout, a cardiologist at Batiment Hospital in Lausanne, Switzerland, reported procedural and 30-day outcome data for the first 800 of the 1,305 patients enrolled in the registry as of May 2014.

Unlike previously reported multicenter series of patients getting BVS, these patients included 46% with at least two affected coronary arteries, 29% with stable angina, 15% with unstable angina, and 35% with an acute or recent MI. Significant calcification was present in 20% of the treated coronaries, 12% of the treated coronary stenoses were located at bifurcations, 12% of the coronaries featured extensive tortuosity, 11% had total occlusions, and 6% had ostial lesions. Lesion complexity scoring based on the American Heart Association and American College of Cardiology method rated 24% of the stenoses type C lesions and another 23% rated as B2 lesions. In addition, 38% of the lesions were at least 20 mm long.

Despite the challenging anatomy that many patients featured, device success occurred in 99% of the patients and procedure success in 98%, reported Dr. Eeckhout. Bailout treatment with a metal stent was needed in five patients (0.6%). During the 30 days following treatment the 800 patients had no deaths, and two cases (0.3%) of definite or probably stent thrombosis with both episodes occurring 1-30 days after scaffold placement – low rates given the complexity of the patients and lesions treated.

"These findings suggest the early safety and performance of Absorb in complex, real-world patients in daily PCI use," Dr. Eeckhout said. "Probably the operators [who treated these 800 patients] knew how to handle a BVS and they were able to expand to more complex pathology without an impact on safety or efficacy," he noted, adding that the "excellent results reflect the increasing experience of interventional cardiologists who use BVS; complexity did not impact efficacy or safety."

"These were "extraordinarily good outcomes in very complex patients," commented Dr. Stone, but he cautioned that the follow-up so far has been brief and that this was a "self-reported" registry, so it is possible that some operators failed to report some of their complications.

Other registry data reported at EuroPCR had longer follow-up, in some cases out to as long as 1 year, but in smaller patient sets and at fewer centers. These series represent "real world" use of BVS at these centers since Absorb came onto the European market in September 2012. Soon after BVS became commercially available, the interventionalists at these centers decided to use them in whichever patients they could regardless of their clinical status – in patients with acute coronary syndrome as well as stable patients, and regardless of lesion type or location. This contrasted with the initial, preapproval trials of BVS that excluded unstable patients and patients with complex coronary lesions or lesions in challenging sites, such as bifurcations or at an arterial ostium.

Findings from several ongoing registries were reported at EuroPCR:

• A group of six German centers had 1-year follow-up on 181 patients. Two thirds had class B2 or C lesions, 16% of lesions were calcified, and 14% involved side branches. These patients had a 5% rate of major adverse coronary events in the first year with no episodes of stent thrombosis, a result comparable with the pivotal trials for second-generation drug-eluting metallic stents as well as the early BVS studies that enrolled patients with simpler lesions, noted Dr. Thomas Schmitz, a cardiologist at the Contilla Heart and Vascular Center in Essen, Germany.

• Single-center experience at the Thoraxcenter in Rotterdam included 6-month follow-up on the first 180 of what are now more than 600 patients who have received BVS at the Thoraxcenter since it came onto the market. The series featured 48% of patients with calcified lesions, 41% with type B2 or C lesions, 38% of patients with multivessel disease, and lesion lengths up to 25 mm. Many patients received a BVS acutely after a ST-segment MI. Device success occurred in 98% of patients. The 6-month rate of major adverse coronary events was 3.3%, with definite or probable stent thrombosis in 2%, and 2% required target-lesion revascularization during 6 months of follow-up. "We had very good results in a complex group of patients that is getting closer to the real world by including patients with unstable and stable angina and ST-elevation myocardial infarction," said Dr. Robert-Jan van Geuns, a cardiologist at the Thoraxcenter. "We got stentlike results using a temporary scaffold. But we want to improve the flexibility of the BVS, reduce strut thickness, and make the procedures easier," he said.

• Interventionalists at Ferrarotto University Hospital in Catania, Italy, decided in March 2013 to start placing BVS when they could "regardless of lesion location or complexity." By this past May they had treated 367 lesions in 289 patients with BVS and had 6-month follow-up on 169 patients and 12-month follow-up on 48, said Dr. Corrado Tamburino, professor of cardiology and director of clinical cardiology at Ferrarotto. Half of their BVS patients had acute coronary syndrome, including 18% with ST-elevation MI, 17% with unstable angina, and 15% with non-STEMI. Half the treated lesions were class C or B2, 27% of patients had two or more lesions, 16% were at bifurcations, 9% were chronic total occlusions, and the mean lesion length was 21 mm. The operators successfully delivered BVS into 98% of patients. Among patients with 6-months’ follow-up, the incidence of major adverse coronary events was 2%, with no episodes of stent thrombosis after 30 days. The series included two deaths: one in a patient who stopped dual-antiplatelet therapy (DAPT) after 25 days and another in a patient who had an arterial dissection. All the BVS thromboses occurred within the first 30 days, "meaning it’s a technical issue. You need to always do lesion preparation, proper sizing [of the BVS for the artery it is entering], and post dilatation. If you do all that, you reduce the risk of thrombosis," he explained. The findings showed that placing "BVS is feasible and safe in the real world, and is effective at midterm follow-up. Stent thrombosis is not an issue if the procedural steps are respected. We expect similar results after 1 and 2 years, but we need to wait and be cautious," Dr. Tamburino said.

• Several centers in Poland began last year to enroll consecutive patients with acute coronary syndrome and culprit lesions that were amenable to BVS treatment. By May they had 1-year follow-up data on 94 BVS recipients, mostly patients with unstable angina or non–ST-elevation MI (NSTEMI) but also several with STEMI. The series had 100% success for BVS delivery and device success, with a 3% rate of major adverse coronary events while the patients remained initially hospitalized. After 12 months the patients had no deaths, three MIs, one target vessel revascularization, and one non–target vessel revascularization. Stent thrombosis occurred in one patient who prematurely stopped DAPT. The series so far has had no need for target-lesion revascularization. The 1-year results "show excellent outcomes. I’m amazed the results have been so good," said Dr. Dariusz Dudek, a cardiologist at University Hospital in Krakow, Poland.

• Interventionalists at two centers in Prague saw 311 consecutive patients with STEMI from December 2012 through the end of April 2014, and among these patients 79 (25%) met the group’s criteria for treatment with BVS. The operators excluded patients with a high likelihood of dying during the 2-3 year period for full BVS disappearance, with a Killip class of III or IV. They also excluded patients with an infarct-related artery less than 2.3 mm in diameter or more than 3.7 mm because of the limited size availability of BVS and because of the dangers from using incorrectly sized BVS. The 79 patients who received a BVS were a third of all patients in the series who received some form of PCI. An analysis presented by Dr. Petr Widimský, professor and head of the department of cardiology at Vinohrady Teaching Hospital in Prague, compared 9-month outcomes for these 79 patients who received BVS and 184 patients from the same series who also had Killip class I or II disease at the time of PCI. The remaining 48 patients from the series had Killip class III or IV disease and were excluded. After 9 months, event-free survival rate was 95% in the BVS recipients and 90% in the patients who received PCI with metallic stents, a nonsignificant difference. In the BVS group, 76 of the 79 patients successfully received a total of 85 BVS. Seventy-two of the 76 who received a BVS had an "ideal" procedural result, with no dissections and achievement of full blood flow through the treated lesion; the other four patients had slightly compromised blood flow after BVS placement. The 76 patients who successfully received a BVS had one death 4 hours after PCI as a result of septal rupture, and another BVS thrombosis 3 days after the patient stopped DAPT. A stroke or transient ischemic attack occurred in three patients. "We conclude that using BVS to treat acute STEMI is feasible and safe, and with currently available BVS sizes can be done in 25%-33% of STEMI patients. Having a 4.0-mm diameter BVS would substantially increase the number of patients we could treat," Dr. Widimský said.

• Cardiologists at one center in Barcelona treated 67 chronic total occlusions (CTO) since BVS became available, 49 of which could be crossed with a guidewire. Of these, the interventionalists could place a BVS in 38 patients; they excluded the other 11 patients because of excessive coronary-artery tortuosity, bifurcated lesions, or inappropriate vessel size. Among the 38 CTO patients who received BVS, three required bail-out PCI with a metallic stent because of a dissection. Average CTO length was 19 mm, and the average total lesion length was 36 mm. At 1-month follow-up, there were no deaths, no MI, no need for additional revascularization, and no BVS thrombosis. The same pattern held among the 33 patients from this group who had 6-months’ follow-up. "These surprising, extremely good results seem too good to be true," said Dr. Antonio Serra, an interventional cardiologist at Hospital Sant Pau in Barcelona. Results from the series so far "show that BVS is extremely feasible and safe for treating complex CTO. We report excellent patency and safety. The results at 6 months were outstanding."

Limits on BVS use

BVS are not for everyone. They get ruled out by substantial tortuosity of the route from the catheterization site to the affected coronary because BVS are stiffer than metallic stents and less amenable to pass through a winding arterial route. Patients need to be good candidates to remain on DAPT for at least 12 months, and the target-vessel diameter cannot veer too far from the currently available BVS diameters of 2.5, 3.0, or 3.5 mm. In most centers, these and other exclusion criteria usually rule out 75%-85% of patients, said several experienced BVS interventionalists at the meeting.

"I want patients who are healthy enough so they stay on DAPT. A BVS is not where you try 3 or 6 months of DAPT," said Dr. van Geuns. He also said that he would not use BVS for treating venous grafts, nor for in-stent restenosis because the existing metal likely would prevent late-lumen enlargement. And in some patients BVS cannot reach the lesion site despite aggressive predilation and vessel preparation.

"We’ve seen increasing breadth of use in the real world. It’s not yet true 100% all-comers, because appropriately people are learning where to use this technology," commented Dr. Stone.

"Our data represent a bias because it is not 100% of our patient population. They are the patients whom we think it is possible to implant a BVS," Dr. Tamburino said.

BVS "technology is not forgiving," Dr. van Guens pointed out. "If you leave a small lumen you will get a small lumen, and that can cause flow disturbances and perhaps a thrombus. Sometimes we are too eager with this technology. I think we can get to 100% in the future, but we should go slow because we are not there yet." He added that the number of BVS recipients and the rate of stent thrombosis were so far too small to allow meaningful analysis of which BVS recipients faced the greatest risk of stent thrombosis. Possible factors include inadequate post dilitation of the BVS, overexpansion of a BVS, and premature halt of DAPT.

"BVS is now feasible to use for every case" as long as the target vessel is no more than 10% smaller than the available BVS, Dr. Julinda Mehilli, an interventional cardiologist at the German Heart Center in Munich, said in a talk at the meeting. Preferred locations are long lesions in distal segments. Operators should be cautious using BVS to treat bifurcations, arteries with pronounced tortuosity, or arteries with moderate to severe calcification. When two BVS are needed in tandem, they should be placed as close to edge to edge as possible. She also stressed the need for systematic attention to every phase of BVS preparation and delivery, starting from selecting the appropriate BVS diameter to match the target vessel, predilation of the lesion and vessel and removal of calcium, gradual inflation of the BVS itself, and then followed by post dilitation of the BVS with a noncompliant balloon, ideally for at least 20 seconds.

"Now that we have BVS, it is the device of choice for chronic total occlusions because long term there is healing of the vessel walls when we use BVS. We often see long-term malopposition of stent struts in chronic total occlusions. With BVS the scaffold will disappear," eliminating the malopposition risk, Dr. Mehilli said.

Dr. Stone had no relevant disclosures, but he is lead investigator for an ongoing trial studying Abbot Vascular’s Absorb BVS. Dr. Serruys, Dr. Eeckhout, Dr. Schmitz, Dr. Dudek, and Dr. Serra had no disclosures. Dr. Tamburino is a consultant to Abbott Vascular and three other companies. Dr. Simonton is an employee of Abbott Vascular. Dr. van Geuns has received honoraria and research support from Abbott Vascular and other companies. Dr. Widimský has received honoraria from Abbott Vascular and other companies. Dr. Mehilli has received lecture fees from Abbott Vascular and other companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – Bioabsorbable vascular scaffolds have caught on in Europe and elsewhere in the world as an alternative to conventional metal stents for percutaneous coronary interventions in a wide spectrum of patient types.

By May 2014, more than 50,000 bioabsorbable vascular scaffolds (BVS) of the first brand to enter the European market – the Absorb stent made by Abbott Vascular – had gone into patients since the first placement in 2007, with the vast majority placed since this scaffold entered the European market in September 2012. Use of BVS in the United States remains investigational, while in the 20-plus months since BVS first became available in Europe other brands of BVS also have entered that market.

©wildpixel/iStockphoto.com

Despite growing BVS use in Europe, as well as in Asia and Central and South America, where they are also available, large-scale data on the consequences, especially long-term consequences, of BVS placement are mostly lacking, particularly data on how BVS perform when directly compared with drug-eluting metallic stents.

"Today we have uncontrolled dissemination of the technology without comparative data," Dr. Patrick W. Serruys, a pioneer in using BVS, said during a session at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

"We need evidence to know exactly what to do" with BVS, which patients to use them in, and when they are preferable to metallic stents, said Dr. Serruys, an interventional cardiologist and professor of medicine at the Thoraxcenter of Erasmus University in Rotterdam, the Netherlands.

"In the 7 years I’ve used them, in patients with 5-year follow-up, there have been no negative signals," he said in an interview, discussing his part of the sizeable anecdotal experience that BVS are safe and effective.

Several large trials comparing BVS with metal stents are in progress, including U.S. pivotal trials, but until these results are out, all that interventionalists have to gauge BVS performance are results from registries and uncontrolled trials. Given that limitation, so far the data look uniformly excellent.

"It is clear that emerging data from real-world, expanded-use registries suggest that use of the Absorb BVS is feasible and safe in a variety of patients, from low to high risk, and from simple to complex lesions," said Dr. Gregg W. Stone in a talk at the meeting. "But attention to procedural detail and technique is essential to optimize the outcomes. BVS are a little more complicated than metallic drug-eluting stents," said Dr. Stone, professor and director of cardiovascular research and education at Columbia University in New York.

"Data from large, randomized controlled trials are necessary to demonstrate whether BVS truly improve outcomes compared with best-in-class metallic stents. We are still early in the technology," he said. Dr. Stone is a lead investigator for one of the large U.S. randomized trials comparing the Absorb BVS to the current standard for percutaneous coronary interventions, a second-generation drug-eluting metallic stent.

Hints of what BVS may deliver

Hints of some of the potential benefits that BVS might provide appeared in results from a post-hoc, across-studies analysis that Dr. Stone presented in his talk. He compared the incidence of angina during the first year following PCI in 287 patients from the Absorb EXTEND study and 602 patients who received coronary stenting with the Xience second-generation everolimus-eluting metallic stent in the SPIRIT IV trial. The analysis matched patients in the Absorb arm with those in the Xience arm by propensity scoring.

The 1-year angina rates were 28% for the patients who received a metallic stent and 16% for those who received an absorbable scaffold, a 12% absolute difference, with a hazard ratio showing a 47% relative reduction in angina in patients who received the BVS, Dr. Stone reported. "There are a variety of mechanisms" by which BVS might reduce the rate of angina compared with metallic stents, including restoration of cyclic pulsatility in the treated arteries and improved vasomotion, he said.

The two outstanding clinical issues that dog PCI with second-generation drug-eluting metallic stents are the accrual of "very late" adverse events and the slow return of angina, with an average rate of target lesion failure with second-generation stents of about 1.8% year that continues out for at least 5 years, he said. "Can BVS flatten out the ongoing event rate" and improve measures like recurrent angina? Dr. Stone asked.

In another cross-study comparison, Dr. Serruys cited a recent, still unpublished analysis on which he collaborated that compared the 1-year outcomes of 102 patients with diabetes who received a BVS and 172 patients with diabetes who received a second-generation drug-eluting metallic stent. The 12-month cumulative rate of cardiovascular death, myocardial infarction, or ischemia-driven target lesion revascularization was 34.9% in the BVS recipients and 6.4% in patients who received state-of-the-art drug-eluting stents.

The working hypothesis behind BVS is that, by dissolving during a period of 12-24 months, the scaffold provides temporary bracing against restenosis but then disappears, allowing improved endovascular healing. During a separate session at EuroPCR, Dr. Charles A. Simonton, an interventional cardiologist and chief medical officer for Abbott Vascular, described the hypothesized impact that bioabsorbable coronary stents might have.

"Our vision is to convert interventional cardiology from mechanically oriented, plumbing-type interventions where you do mechanical things to open arteries" to a focus on tissue regeneration. "What we see when scaffolds resorb is that, at 3-5 years, the arteries look very different from what we see with a metal stent. The vessels show a highly functional neointimal layer that is functioning smooth muscle cells that protect against rupture in underlying plaque," he said.

Having BVS will allow interventional cardiologists to "transition from being mechanical plumbers to really being medical doctors. Not just opening lesions but putting in a treatment that can improve patients long term," Dr. Simonton said, presenting his best-case prediction of what BVS might achieve. "We need to generate a lot of data to make sure this is real," he added, in something of an understatement.

"There is late lumen enlargement with BVS. That is a clear fact," said Dr. Serruys.

The BVS experience

With data from studies that directly compared BVS and metallic stents still a few years off, the only indications of BVS performance now available come from either single- or multicenter registries. The thrust of much of these data presented at EuroPCR was that BVS have performed well as interventionalists have moved in the months since BVS became available for routine use to placing them in sicker patients and in patients with more complex coronary lesions.

Mitchel L. Zoler/Frontline Medical News

The largest registry is ABSORB First, a voluntary-reporting registry that began in January 2013 and involves about 90 centers in countries where Absorb is commercially available in Europe, Asia, New Zealand, and Columbia. Dr. Eric Eeckhout, a cardiologist at Batiment Hospital in Lausanne, Switzerland, reported procedural and 30-day outcome data for the first 800 of the 1,305 patients enrolled in the registry as of May 2014.

Unlike previously reported multicenter series of patients getting BVS, these patients included 46% with at least two affected coronary arteries, 29% with stable angina, 15% with unstable angina, and 35% with an acute or recent MI. Significant calcification was present in 20% of the treated coronaries, 12% of the treated coronary stenoses were located at bifurcations, 12% of the coronaries featured extensive tortuosity, 11% had total occlusions, and 6% had ostial lesions. Lesion complexity scoring based on the American Heart Association and American College of Cardiology method rated 24% of the stenoses type C lesions and another 23% rated as B2 lesions. In addition, 38% of the lesions were at least 20 mm long.

Despite the challenging anatomy that many patients featured, device success occurred in 99% of the patients and procedure success in 98%, reported Dr. Eeckhout. Bailout treatment with a metal stent was needed in five patients (0.6%). During the 30 days following treatment the 800 patients had no deaths, and two cases (0.3%) of definite or probably stent thrombosis with both episodes occurring 1-30 days after scaffold placement – low rates given the complexity of the patients and lesions treated.

"These findings suggest the early safety and performance of Absorb in complex, real-world patients in daily PCI use," Dr. Eeckhout said. "Probably the operators [who treated these 800 patients] knew how to handle a BVS and they were able to expand to more complex pathology without an impact on safety or efficacy," he noted, adding that the "excellent results reflect the increasing experience of interventional cardiologists who use BVS; complexity did not impact efficacy or safety."

"These were "extraordinarily good outcomes in very complex patients," commented Dr. Stone, but he cautioned that the follow-up so far has been brief and that this was a "self-reported" registry, so it is possible that some operators failed to report some of their complications.

Other registry data reported at EuroPCR had longer follow-up, in some cases out to as long as 1 year, but in smaller patient sets and at fewer centers. These series represent "real world" use of BVS at these centers since Absorb came onto the European market in September 2012. Soon after BVS became commercially available, the interventionalists at these centers decided to use them in whichever patients they could regardless of their clinical status – in patients with acute coronary syndrome as well as stable patients, and regardless of lesion type or location. This contrasted with the initial, preapproval trials of BVS that excluded unstable patients and patients with complex coronary lesions or lesions in challenging sites, such as bifurcations or at an arterial ostium.

Findings from several ongoing registries were reported at EuroPCR:

• A group of six German centers had 1-year follow-up on 181 patients. Two thirds had class B2 or C lesions, 16% of lesions were calcified, and 14% involved side branches. These patients had a 5% rate of major adverse coronary events in the first year with no episodes of stent thrombosis, a result comparable with the pivotal trials for second-generation drug-eluting metallic stents as well as the early BVS studies that enrolled patients with simpler lesions, noted Dr. Thomas Schmitz, a cardiologist at the Contilla Heart and Vascular Center in Essen, Germany.

• Single-center experience at the Thoraxcenter in Rotterdam included 6-month follow-up on the first 180 of what are now more than 600 patients who have received BVS at the Thoraxcenter since it came onto the market. The series featured 48% of patients with calcified lesions, 41% with type B2 or C lesions, 38% of patients with multivessel disease, and lesion lengths up to 25 mm. Many patients received a BVS acutely after a ST-segment MI. Device success occurred in 98% of patients. The 6-month rate of major adverse coronary events was 3.3%, with definite or probable stent thrombosis in 2%, and 2% required target-lesion revascularization during 6 months of follow-up. "We had very good results in a complex group of patients that is getting closer to the real world by including patients with unstable and stable angina and ST-elevation myocardial infarction," said Dr. Robert-Jan van Geuns, a cardiologist at the Thoraxcenter. "We got stentlike results using a temporary scaffold. But we want to improve the flexibility of the BVS, reduce strut thickness, and make the procedures easier," he said.

• Interventionalists at Ferrarotto University Hospital in Catania, Italy, decided in March 2013 to start placing BVS when they could "regardless of lesion location or complexity." By this past May they had treated 367 lesions in 289 patients with BVS and had 6-month follow-up on 169 patients and 12-month follow-up on 48, said Dr. Corrado Tamburino, professor of cardiology and director of clinical cardiology at Ferrarotto. Half of their BVS patients had acute coronary syndrome, including 18% with ST-elevation MI, 17% with unstable angina, and 15% with non-STEMI. Half the treated lesions were class C or B2, 27% of patients had two or more lesions, 16% were at bifurcations, 9% were chronic total occlusions, and the mean lesion length was 21 mm. The operators successfully delivered BVS into 98% of patients. Among patients with 6-months’ follow-up, the incidence of major adverse coronary events was 2%, with no episodes of stent thrombosis after 30 days. The series included two deaths: one in a patient who stopped dual-antiplatelet therapy (DAPT) after 25 days and another in a patient who had an arterial dissection. All the BVS thromboses occurred within the first 30 days, "meaning it’s a technical issue. You need to always do lesion preparation, proper sizing [of the BVS for the artery it is entering], and post dilatation. If you do all that, you reduce the risk of thrombosis," he explained. The findings showed that placing "BVS is feasible and safe in the real world, and is effective at midterm follow-up. Stent thrombosis is not an issue if the procedural steps are respected. We expect similar results after 1 and 2 years, but we need to wait and be cautious," Dr. Tamburino said.

• Several centers in Poland began last year to enroll consecutive patients with acute coronary syndrome and culprit lesions that were amenable to BVS treatment. By May they had 1-year follow-up data on 94 BVS recipients, mostly patients with unstable angina or non–ST-elevation MI (NSTEMI) but also several with STEMI. The series had 100% success for BVS delivery and device success, with a 3% rate of major adverse coronary events while the patients remained initially hospitalized. After 12 months the patients had no deaths, three MIs, one target vessel revascularization, and one non–target vessel revascularization. Stent thrombosis occurred in one patient who prematurely stopped DAPT. The series so far has had no need for target-lesion revascularization. The 1-year results "show excellent outcomes. I’m amazed the results have been so good," said Dr. Dariusz Dudek, a cardiologist at University Hospital in Krakow, Poland.

• Interventionalists at two centers in Prague saw 311 consecutive patients with STEMI from December 2012 through the end of April 2014, and among these patients 79 (25%) met the group’s criteria for treatment with BVS. The operators excluded patients with a high likelihood of dying during the 2-3 year period for full BVS disappearance, with a Killip class of III or IV. They also excluded patients with an infarct-related artery less than 2.3 mm in diameter or more than 3.7 mm because of the limited size availability of BVS and because of the dangers from using incorrectly sized BVS. The 79 patients who received a BVS were a third of all patients in the series who received some form of PCI. An analysis presented by Dr. Petr Widimský, professor and head of the department of cardiology at Vinohrady Teaching Hospital in Prague, compared 9-month outcomes for these 79 patients who received BVS and 184 patients from the same series who also had Killip class I or II disease at the time of PCI. The remaining 48 patients from the series had Killip class III or IV disease and were excluded. After 9 months, event-free survival rate was 95% in the BVS recipients and 90% in the patients who received PCI with metallic stents, a nonsignificant difference. In the BVS group, 76 of the 79 patients successfully received a total of 85 BVS. Seventy-two of the 76 who received a BVS had an "ideal" procedural result, with no dissections and achievement of full blood flow through the treated lesion; the other four patients had slightly compromised blood flow after BVS placement. The 76 patients who successfully received a BVS had one death 4 hours after PCI as a result of septal rupture, and another BVS thrombosis 3 days after the patient stopped DAPT. A stroke or transient ischemic attack occurred in three patients. "We conclude that using BVS to treat acute STEMI is feasible and safe, and with currently available BVS sizes can be done in 25%-33% of STEMI patients. Having a 4.0-mm diameter BVS would substantially increase the number of patients we could treat," Dr. Widimský said.

• Cardiologists at one center in Barcelona treated 67 chronic total occlusions (CTO) since BVS became available, 49 of which could be crossed with a guidewire. Of these, the interventionalists could place a BVS in 38 patients; they excluded the other 11 patients because of excessive coronary-artery tortuosity, bifurcated lesions, or inappropriate vessel size. Among the 38 CTO patients who received BVS, three required bail-out PCI with a metallic stent because of a dissection. Average CTO length was 19 mm, and the average total lesion length was 36 mm. At 1-month follow-up, there were no deaths, no MI, no need for additional revascularization, and no BVS thrombosis. The same pattern held among the 33 patients from this group who had 6-months’ follow-up. "These surprising, extremely good results seem too good to be true," said Dr. Antonio Serra, an interventional cardiologist at Hospital Sant Pau in Barcelona. Results from the series so far "show that BVS is extremely feasible and safe for treating complex CTO. We report excellent patency and safety. The results at 6 months were outstanding."

Limits on BVS use

BVS are not for everyone. They get ruled out by substantial tortuosity of the route from the catheterization site to the affected coronary because BVS are stiffer than metallic stents and less amenable to pass through a winding arterial route. Patients need to be good candidates to remain on DAPT for at least 12 months, and the target-vessel diameter cannot veer too far from the currently available BVS diameters of 2.5, 3.0, or 3.5 mm. In most centers, these and other exclusion criteria usually rule out 75%-85% of patients, said several experienced BVS interventionalists at the meeting.

"I want patients who are healthy enough so they stay on DAPT. A BVS is not where you try 3 or 6 months of DAPT," said Dr. van Geuns. He also said that he would not use BVS for treating venous grafts, nor for in-stent restenosis because the existing metal likely would prevent late-lumen enlargement. And in some patients BVS cannot reach the lesion site despite aggressive predilation and vessel preparation.

"We’ve seen increasing breadth of use in the real world. It’s not yet true 100% all-comers, because appropriately people are learning where to use this technology," commented Dr. Stone.

"Our data represent a bias because it is not 100% of our patient population. They are the patients whom we think it is possible to implant a BVS," Dr. Tamburino said.

BVS "technology is not forgiving," Dr. van Guens pointed out. "If you leave a small lumen you will get a small lumen, and that can cause flow disturbances and perhaps a thrombus. Sometimes we are too eager with this technology. I think we can get to 100% in the future, but we should go slow because we are not there yet." He added that the number of BVS recipients and the rate of stent thrombosis were so far too small to allow meaningful analysis of which BVS recipients faced the greatest risk of stent thrombosis. Possible factors include inadequate post dilitation of the BVS, overexpansion of a BVS, and premature halt of DAPT.

"BVS is now feasible to use for every case" as long as the target vessel is no more than 10% smaller than the available BVS, Dr. Julinda Mehilli, an interventional cardiologist at the German Heart Center in Munich, said in a talk at the meeting. Preferred locations are long lesions in distal segments. Operators should be cautious using BVS to treat bifurcations, arteries with pronounced tortuosity, or arteries with moderate to severe calcification. When two BVS are needed in tandem, they should be placed as close to edge to edge as possible. She also stressed the need for systematic attention to every phase of BVS preparation and delivery, starting from selecting the appropriate BVS diameter to match the target vessel, predilation of the lesion and vessel and removal of calcium, gradual inflation of the BVS itself, and then followed by post dilitation of the BVS with a noncompliant balloon, ideally for at least 20 seconds.

"Now that we have BVS, it is the device of choice for chronic total occlusions because long term there is healing of the vessel walls when we use BVS. We often see long-term malopposition of stent struts in chronic total occlusions. With BVS the scaffold will disappear," eliminating the malopposition risk, Dr. Mehilli said.

Dr. Stone had no relevant disclosures, but he is lead investigator for an ongoing trial studying Abbot Vascular’s Absorb BVS. Dr. Serruys, Dr. Eeckhout, Dr. Schmitz, Dr. Dudek, and Dr. Serra had no disclosures. Dr. Tamburino is a consultant to Abbott Vascular and three other companies. Dr. Simonton is an employee of Abbott Vascular. Dr. van Geuns has received honoraria and research support from Abbott Vascular and other companies. Dr. Widimský has received honoraria from Abbott Vascular and other companies. Dr. Mehilli has received lecture fees from Abbott Vascular and other companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – Bioabsorbable vascular scaffolds have caught on in Europe and elsewhere in the world as an alternative to conventional metal stents for percutaneous coronary interventions in a wide spectrum of patient types.

By May 2014, more than 50,000 bioabsorbable vascular scaffolds (BVS) of the first brand to enter the European market – the Absorb stent made by Abbott Vascular – had gone into patients since the first placement in 2007, with the vast majority placed since this scaffold entered the European market in September 2012. Use of BVS in the United States remains investigational, while in the 20-plus months since BVS first became available in Europe other brands of BVS also have entered that market.

©wildpixel/iStockphoto.com

Despite growing BVS use in Europe, as well as in Asia and Central and South America, where they are also available, large-scale data on the consequences, especially long-term consequences, of BVS placement are mostly lacking, particularly data on how BVS perform when directly compared with drug-eluting metallic stents.

"Today we have uncontrolled dissemination of the technology without comparative data," Dr. Patrick W. Serruys, a pioneer in using BVS, said during a session at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

"We need evidence to know exactly what to do" with BVS, which patients to use them in, and when they are preferable to metallic stents, said Dr. Serruys, an interventional cardiologist and professor of medicine at the Thoraxcenter of Erasmus University in Rotterdam, the Netherlands.

"In the 7 years I’ve used them, in patients with 5-year follow-up, there have been no negative signals," he said in an interview, discussing his part of the sizeable anecdotal experience that BVS are safe and effective.

Several large trials comparing BVS with metal stents are in progress, including U.S. pivotal trials, but until these results are out, all that interventionalists have to gauge BVS performance are results from registries and uncontrolled trials. Given that limitation, so far the data look uniformly excellent.

"It is clear that emerging data from real-world, expanded-use registries suggest that use of the Absorb BVS is feasible and safe in a variety of patients, from low to high risk, and from simple to complex lesions," said Dr. Gregg W. Stone in a talk at the meeting. "But attention to procedural detail and technique is essential to optimize the outcomes. BVS are a little more complicated than metallic drug-eluting stents," said Dr. Stone, professor and director of cardiovascular research and education at Columbia University in New York.

"Data from large, randomized controlled trials are necessary to demonstrate whether BVS truly improve outcomes compared with best-in-class metallic stents. We are still early in the technology," he said. Dr. Stone is a lead investigator for one of the large U.S. randomized trials comparing the Absorb BVS to the current standard for percutaneous coronary interventions, a second-generation drug-eluting metallic stent.

Hints of what BVS may deliver

Hints of some of the potential benefits that BVS might provide appeared in results from a post-hoc, across-studies analysis that Dr. Stone presented in his talk. He compared the incidence of angina during the first year following PCI in 287 patients from the Absorb EXTEND study and 602 patients who received coronary stenting with the Xience second-generation everolimus-eluting metallic stent in the SPIRIT IV trial. The analysis matched patients in the Absorb arm with those in the Xience arm by propensity scoring.

The 1-year angina rates were 28% for the patients who received a metallic stent and 16% for those who received an absorbable scaffold, a 12% absolute difference, with a hazard ratio showing a 47% relative reduction in angina in patients who received the BVS, Dr. Stone reported. "There are a variety of mechanisms" by which BVS might reduce the rate of angina compared with metallic stents, including restoration of cyclic pulsatility in the treated arteries and improved vasomotion, he said.

The two outstanding clinical issues that dog PCI with second-generation drug-eluting metallic stents are the accrual of "very late" adverse events and the slow return of angina, with an average rate of target lesion failure with second-generation stents of about 1.8% year that continues out for at least 5 years, he said. "Can BVS flatten out the ongoing event rate" and improve measures like recurrent angina? Dr. Stone asked.

In another cross-study comparison, Dr. Serruys cited a recent, still unpublished analysis on which he collaborated that compared the 1-year outcomes of 102 patients with diabetes who received a BVS and 172 patients with diabetes who received a second-generation drug-eluting metallic stent. The 12-month cumulative rate of cardiovascular death, myocardial infarction, or ischemia-driven target lesion revascularization was 34.9% in the BVS recipients and 6.4% in patients who received state-of-the-art drug-eluting stents.

The working hypothesis behind BVS is that, by dissolving during a period of 12-24 months, the scaffold provides temporary bracing against restenosis but then disappears, allowing improved endovascular healing. During a separate session at EuroPCR, Dr. Charles A. Simonton, an interventional cardiologist and chief medical officer for Abbott Vascular, described the hypothesized impact that bioabsorbable coronary stents might have.

"Our vision is to convert interventional cardiology from mechanically oriented, plumbing-type interventions where you do mechanical things to open arteries" to a focus on tissue regeneration. "What we see when scaffolds resorb is that, at 3-5 years, the arteries look very different from what we see with a metal stent. The vessels show a highly functional neointimal layer that is functioning smooth muscle cells that protect against rupture in underlying plaque," he said.

Having BVS will allow interventional cardiologists to "transition from being mechanical plumbers to really being medical doctors. Not just opening lesions but putting in a treatment that can improve patients long term," Dr. Simonton said, presenting his best-case prediction of what BVS might achieve. "We need to generate a lot of data to make sure this is real," he added, in something of an understatement.

"There is late lumen enlargement with BVS. That is a clear fact," said Dr. Serruys.

The BVS experience

With data from studies that directly compared BVS and metallic stents still a few years off, the only indications of BVS performance now available come from either single- or multicenter registries. The thrust of much of these data presented at EuroPCR was that BVS have performed well as interventionalists have moved in the months since BVS became available for routine use to placing them in sicker patients and in patients with more complex coronary lesions.

Mitchel L. Zoler/Frontline Medical News

The largest registry is ABSORB First, a voluntary-reporting registry that began in January 2013 and involves about 90 centers in countries where Absorb is commercially available in Europe, Asia, New Zealand, and Columbia. Dr. Eric Eeckhout, a cardiologist at Batiment Hospital in Lausanne, Switzerland, reported procedural and 30-day outcome data for the first 800 of the 1,305 patients enrolled in the registry as of May 2014.

Unlike previously reported multicenter series of patients getting BVS, these patients included 46% with at least two affected coronary arteries, 29% with stable angina, 15% with unstable angina, and 35% with an acute or recent MI. Significant calcification was present in 20% of the treated coronaries, 12% of the treated coronary stenoses were located at bifurcations, 12% of the coronaries featured extensive tortuosity, 11% had total occlusions, and 6% had ostial lesions. Lesion complexity scoring based on the American Heart Association and American College of Cardiology method rated 24% of the stenoses type C lesions and another 23% rated as B2 lesions. In addition, 38% of the lesions were at least 20 mm long.

Despite the challenging anatomy that many patients featured, device success occurred in 99% of the patients and procedure success in 98%, reported Dr. Eeckhout. Bailout treatment with a metal stent was needed in five patients (0.6%). During the 30 days following treatment the 800 patients had no deaths, and two cases (0.3%) of definite or probably stent thrombosis with both episodes occurring 1-30 days after scaffold placement – low rates given the complexity of the patients and lesions treated.

"These findings suggest the early safety and performance of Absorb in complex, real-world patients in daily PCI use," Dr. Eeckhout said. "Probably the operators [who treated these 800 patients] knew how to handle a BVS and they were able to expand to more complex pathology without an impact on safety or efficacy," he noted, adding that the "excellent results reflect the increasing experience of interventional cardiologists who use BVS; complexity did not impact efficacy or safety."

"These were "extraordinarily good outcomes in very complex patients," commented Dr. Stone, but he cautioned that the follow-up so far has been brief and that this was a "self-reported" registry, so it is possible that some operators failed to report some of their complications.

Other registry data reported at EuroPCR had longer follow-up, in some cases out to as long as 1 year, but in smaller patient sets and at fewer centers. These series represent "real world" use of BVS at these centers since Absorb came onto the European market in September 2012. Soon after BVS became commercially available, the interventionalists at these centers decided to use them in whichever patients they could regardless of their clinical status – in patients with acute coronary syndrome as well as stable patients, and regardless of lesion type or location. This contrasted with the initial, preapproval trials of BVS that excluded unstable patients and patients with complex coronary lesions or lesions in challenging sites, such as bifurcations or at an arterial ostium.

Findings from several ongoing registries were reported at EuroPCR:

• A group of six German centers had 1-year follow-up on 181 patients. Two thirds had class B2 or C lesions, 16% of lesions were calcified, and 14% involved side branches. These patients had a 5% rate of major adverse coronary events in the first year with no episodes of stent thrombosis, a result comparable with the pivotal trials for second-generation drug-eluting metallic stents as well as the early BVS studies that enrolled patients with simpler lesions, noted Dr. Thomas Schmitz, a cardiologist at the Contilla Heart and Vascular Center in Essen, Germany.

• Single-center experience at the Thoraxcenter in Rotterdam included 6-month follow-up on the first 180 of what are now more than 600 patients who have received BVS at the Thoraxcenter since it came onto the market. The series featured 48% of patients with calcified lesions, 41% with type B2 or C lesions, 38% of patients with multivessel disease, and lesion lengths up to 25 mm. Many patients received a BVS acutely after a ST-segment MI. Device success occurred in 98% of patients. The 6-month rate of major adverse coronary events was 3.3%, with definite or probable stent thrombosis in 2%, and 2% required target-lesion revascularization during 6 months of follow-up. "We had very good results in a complex group of patients that is getting closer to the real world by including patients with unstable and stable angina and ST-elevation myocardial infarction," said Dr. Robert-Jan van Geuns, a cardiologist at the Thoraxcenter. "We got stentlike results using a temporary scaffold. But we want to improve the flexibility of the BVS, reduce strut thickness, and make the procedures easier," he said.

• Interventionalists at Ferrarotto University Hospital in Catania, Italy, decided in March 2013 to start placing BVS when they could "regardless of lesion location or complexity." By this past May they had treated 367 lesions in 289 patients with BVS and had 6-month follow-up on 169 patients and 12-month follow-up on 48, said Dr. Corrado Tamburino, professor of cardiology and director of clinical cardiology at Ferrarotto. Half of their BVS patients had acute coronary syndrome, including 18% with ST-elevation MI, 17% with unstable angina, and 15% with non-STEMI. Half the treated lesions were class C or B2, 27% of patients had two or more lesions, 16% were at bifurcations, 9% were chronic total occlusions, and the mean lesion length was 21 mm. The operators successfully delivered BVS into 98% of patients. Among patients with 6-months’ follow-up, the incidence of major adverse coronary events was 2%, with no episodes of stent thrombosis after 30 days. The series included two deaths: one in a patient who stopped dual-antiplatelet therapy (DAPT) after 25 days and another in a patient who had an arterial dissection. All the BVS thromboses occurred within the first 30 days, "meaning it’s a technical issue. You need to always do lesion preparation, proper sizing [of the BVS for the artery it is entering], and post dilatation. If you do all that, you reduce the risk of thrombosis," he explained. The findings showed that placing "BVS is feasible and safe in the real world, and is effective at midterm follow-up. Stent thrombosis is not an issue if the procedural steps are respected. We expect similar results after 1 and 2 years, but we need to wait and be cautious," Dr. Tamburino said.

• Several centers in Poland began last year to enroll consecutive patients with acute coronary syndrome and culprit lesions that were amenable to BVS treatment. By May they had 1-year follow-up data on 94 BVS recipients, mostly patients with unstable angina or non–ST-elevation MI (NSTEMI) but also several with STEMI. The series had 100% success for BVS delivery and device success, with a 3% rate of major adverse coronary events while the patients remained initially hospitalized. After 12 months the patients had no deaths, three MIs, one target vessel revascularization, and one non–target vessel revascularization. Stent thrombosis occurred in one patient who prematurely stopped DAPT. The series so far has had no need for target-lesion revascularization. The 1-year results "show excellent outcomes. I’m amazed the results have been so good," said Dr. Dariusz Dudek, a cardiologist at University Hospital in Krakow, Poland.

• Interventionalists at two centers in Prague saw 311 consecutive patients with STEMI from December 2012 through the end of April 2014, and among these patients 79 (25%) met the group’s criteria for treatment with BVS. The operators excluded patients with a high likelihood of dying during the 2-3 year period for full BVS disappearance, with a Killip class of III or IV. They also excluded patients with an infarct-related artery less than 2.3 mm in diameter or more than 3.7 mm because of the limited size availability of BVS and because of the dangers from using incorrectly sized BVS. The 79 patients who received a BVS were a third of all patients in the series who received some form of PCI. An analysis presented by Dr. Petr Widimský, professor and head of the department of cardiology at Vinohrady Teaching Hospital in Prague, compared 9-month outcomes for these 79 patients who received BVS and 184 patients from the same series who also had Killip class I or II disease at the time of PCI. The remaining 48 patients from the series had Killip class III or IV disease and were excluded. After 9 months, event-free survival rate was 95% in the BVS recipients and 90% in the patients who received PCI with metallic stents, a nonsignificant difference. In the BVS group, 76 of the 79 patients successfully received a total of 85 BVS. Seventy-two of the 76 who received a BVS had an "ideal" procedural result, with no dissections and achievement of full blood flow through the treated lesion; the other four patients had slightly compromised blood flow after BVS placement. The 76 patients who successfully received a BVS had one death 4 hours after PCI as a result of septal rupture, and another BVS thrombosis 3 days after the patient stopped DAPT. A stroke or transient ischemic attack occurred in three patients. "We conclude that using BVS to treat acute STEMI is feasible and safe, and with currently available BVS sizes can be done in 25%-33% of STEMI patients. Having a 4.0-mm diameter BVS would substantially increase the number of patients we could treat," Dr. Widimský said.

• Cardiologists at one center in Barcelona treated 67 chronic total occlusions (CTO) since BVS became available, 49 of which could be crossed with a guidewire. Of these, the interventionalists could place a BVS in 38 patients; they excluded the other 11 patients because of excessive coronary-artery tortuosity, bifurcated lesions, or inappropriate vessel size. Among the 38 CTO patients who received BVS, three required bail-out PCI with a metallic stent because of a dissection. Average CTO length was 19 mm, and the average total lesion length was 36 mm. At 1-month follow-up, there were no deaths, no MI, no need for additional revascularization, and no BVS thrombosis. The same pattern held among the 33 patients from this group who had 6-months’ follow-up. "These surprising, extremely good results seem too good to be true," said Dr. Antonio Serra, an interventional cardiologist at Hospital Sant Pau in Barcelona. Results from the series so far "show that BVS is extremely feasible and safe for treating complex CTO. We report excellent patency and safety. The results at 6 months were outstanding."

Limits on BVS use

BVS are not for everyone. They get ruled out by substantial tortuosity of the route from the catheterization site to the affected coronary because BVS are stiffer than metallic stents and less amenable to pass through a winding arterial route. Patients need to be good candidates to remain on DAPT for at least 12 months, and the target-vessel diameter cannot veer too far from the currently available BVS diameters of 2.5, 3.0, or 3.5 mm. In most centers, these and other exclusion criteria usually rule out 75%-85% of patients, said several experienced BVS interventionalists at the meeting.

"I want patients who are healthy enough so they stay on DAPT. A BVS is not where you try 3 or 6 months of DAPT," said Dr. van Geuns. He also said that he would not use BVS for treating venous grafts, nor for in-stent restenosis because the existing metal likely would prevent late-lumen enlargement. And in some patients BVS cannot reach the lesion site despite aggressive predilation and vessel preparation.

"We’ve seen increasing breadth of use in the real world. It’s not yet true 100% all-comers, because appropriately people are learning where to use this technology," commented Dr. Stone.

"Our data represent a bias because it is not 100% of our patient population. They are the patients whom we think it is possible to implant a BVS," Dr. Tamburino said.

BVS "technology is not forgiving," Dr. van Guens pointed out. "If you leave a small lumen you will get a small lumen, and that can cause flow disturbances and perhaps a thrombus. Sometimes we are too eager with this technology. I think we can get to 100% in the future, but we should go slow because we are not there yet." He added that the number of BVS recipients and the rate of stent thrombosis were so far too small to allow meaningful analysis of which BVS recipients faced the greatest risk of stent thrombosis. Possible factors include inadequate post dilitation of the BVS, overexpansion of a BVS, and premature halt of DAPT.

"BVS is now feasible to use for every case" as long as the target vessel is no more than 10% smaller than the available BVS, Dr. Julinda Mehilli, an interventional cardiologist at the German Heart Center in Munich, said in a talk at the meeting. Preferred locations are long lesions in distal segments. Operators should be cautious using BVS to treat bifurcations, arteries with pronounced tortuosity, or arteries with moderate to severe calcification. When two BVS are needed in tandem, they should be placed as close to edge to edge as possible. She also stressed the need for systematic attention to every phase of BVS preparation and delivery, starting from selecting the appropriate BVS diameter to match the target vessel, predilation of the lesion and vessel and removal of calcium, gradual inflation of the BVS itself, and then followed by post dilitation of the BVS with a noncompliant balloon, ideally for at least 20 seconds.

"Now that we have BVS, it is the device of choice for chronic total occlusions because long term there is healing of the vessel walls when we use BVS. We often see long-term malopposition of stent struts in chronic total occlusions. With BVS the scaffold will disappear," eliminating the malopposition risk, Dr. Mehilli said.

Dr. Stone had no relevant disclosures, but he is lead investigator for an ongoing trial studying Abbot Vascular’s Absorb BVS. Dr. Serruys, Dr. Eeckhout, Dr. Schmitz, Dr. Dudek, and Dr. Serra had no disclosures. Dr. Tamburino is a consultant to Abbott Vascular and three other companies. Dr. Simonton is an employee of Abbott Vascular. Dr. van Geuns has received honoraria and research support from Abbott Vascular and other companies. Dr. Widimský has received honoraria from Abbott Vascular and other companies. Dr. Mehilli has received lecture fees from Abbott Vascular and other companies.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – Transcatheter mitral valve replacement finally took off this year, but it may keep a low profile short-term as investigators gain more clinical experience with transcatheter systems and slowly start to define the right types of patients for this procedure.

Transcatheter mitral valve replacement (TMVR) had something of a false start 2 years ago when CardiAQ announced the first clinical case of a patient with severe mitral valve regurgitation who underwent valve replacement using a transcatheter system at the Heart Centre of Rigshospitalet University Hospital, Copenhagen. Further details of that first case have not yet been reported. It was not until this past May that a second patient underwent TMVR performed by the same Danish team, using a second-generation CardiAQ system.

Mitchel L. Zoler/Frontline Medical News

Also this year came reports on two new TMVR systems, each used for the first time clinically, with five patients treated with the Fortis system made by Edwards Lifesciences, and two treated with the Tiara system made by Neovasc.

"We are finally on the journey of assessment of multiple transcatheter mitral valves. We’ve been saying that for a number of years, but it seems like now we truly will see progress in the mitral space," Dr. Martyn Thomas said during a talk at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

At the meeting, Dr. Thomas, an interventional cardiologist at St. Thomas’ Hospital, London, and his associate Vinayak Bapat, a cardiac surgeon, reported the experience with five patients treated with the Fortis valve system, including three patients treated by them and their colleagues in London, one patient in Bern, Switzerland, and a fifth who had been treated in Toronto just 4 days before their report at the meeting.

"We have shown that we can deploy the valve, that the valve functions; and we have one patient who is gradually improving, so I believe that the principle is now there as long as we can find the patients" best suited to TMVR, Dr. Thomas said.

"Patient selection is everything," he noted. The selection process is "perhaps more difficult than for transcatheter aortic valve replacement." Patients with severe mitral valve regurgitation often have substantial comorbidities such as left ventricular dysfunction, pulmonary disease, and renal disease, and these may mean a much longer delay to see patient improvement following TMVR compared with after an aortic valve is replaced, he noted.

Mitchel L. Zoler/Frontline Medical News

"Valve replacement seeks to eliminate mitral regurgitation, while clip systems attempt to reduce regurgitation by about one grade. We need to do both, and the difficulty will be determining which patients should get what treatment," Dr. Thomas said in an interview. "Perhaps the highest-risk patients should undergo repair" with a clip, he suggested.

"We need to select patients who will survive the [TMVR] procedure and get through the following 3 months because we may not see any benefit for 3-6 months, in contrast to aortic valve patients who recover and improve very quickly. I believe we will develop a complex algorithm based on each patient’s anatomy that will address the procedure’s risk and its potential to eliminate mitral regurgitation. The mitral clip is a relatively safe procedure, so it will be a much more complex algorithm than for the aortic valve."

A second report at the meeting reviewed experience with the first two patients who received the Tiara TMVR system, both at St. Paul’s Hospital in Vancouver, B.C. Like the Fortis valve, the Tiara is delivered by a transapical approach. The Tiara system delivers a mitral valve via a 32F catheter; the size of the Fortis catheter has not been reported, but a spokeswoman for Edwards acknowledged that it was a similarly large catheter and that efforts are ongoing to try to cut the catheter size. The Fortis mitral valve is 29 mm in diameter, while the size of the Tiara valve has not been reported. Procedure times for the two Tiara cases were 20 minutes for the first patient and 12 minutes for the second, reported Dr. Anson W. Cheung, surgical director of cardiac transplantation at St. Paul’s. The Fortis valve cases showed a learning curve similar to that of the Tiara cases, with the Fortis procedure time falling from 93 minutes for the first patient to 34 minutes for the fourth.

"The key is to catch patients before their left ventricle burns out, and to prevent the vicious cycle of high afterloading" that can occur when the mitral valve is replaced, Dr. Cheung said. He reported that his two cases had no complications or left ventricular outflow tract obstruction, and that one patient has now survived more than 3 months and has shown improved heart function and a halving of her baseline blood level of brain natriuretic peptide.

Mitchel L. Zoler/Frontline Medical News

"In patients with aortic stenosis, when you remove the obstructed [aortic] valve, they improve. In patients with mitral regurgitation, who develop very severely depressed left ventricular function, once you correct the regurgitation it increases stress on the ventricle and they can get into trouble," commented Dr. William Wijns, codirector of the Cardiovascular Center in Aalst, Belgium. "The complexity of the mitral valve problem is several orders of magnitude greater than with transcatheter aortic valve replacement," Dr. Wijns said.

Dr. Thomas has been a consultant to and has received research support from Edwards, the company developing the Fortis valve. Mr. Bapat has been a consultant to Edwards, Medtronic, and St. Jude and has received research support from Edwards. Dr. Cheung has been a consultant to and received honoraria from Neovasc, the company developing the Tiara valve. Dr. Wijns has received grant support to his institution from Edwards and 15 other companies, and he owns stock in two health care companies and a biotechnology company.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – Transcatheter mitral valve replacement finally took off this year, but it may keep a low profile short-term as investigators gain more clinical experience with transcatheter systems and slowly start to define the right types of patients for this procedure.

Transcatheter mitral valve replacement (TMVR) had something of a false start 2 years ago when CardiAQ announced the first clinical case of a patient with severe mitral valve regurgitation who underwent valve replacement using a transcatheter system at the Heart Centre of Rigshospitalet University Hospital, Copenhagen. Further details of that first case have not yet been reported. It was not until this past May that a second patient underwent TMVR performed by the same Danish team, using a second-generation CardiAQ system.

Mitchel L. Zoler/Frontline Medical News

Also this year came reports on two new TMVR systems, each used for the first time clinically, with five patients treated with the Fortis system made by Edwards Lifesciences, and two treated with the Tiara system made by Neovasc.

"We are finally on the journey of assessment of multiple transcatheter mitral valves. We’ve been saying that for a number of years, but it seems like now we truly will see progress in the mitral space," Dr. Martyn Thomas said during a talk at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

At the meeting, Dr. Thomas, an interventional cardiologist at St. Thomas’ Hospital, London, and his associate Vinayak Bapat, a cardiac surgeon, reported the experience with five patients treated with the Fortis valve system, including three patients treated by them and their colleagues in London, one patient in Bern, Switzerland, and a fifth who had been treated in Toronto just 4 days before their report at the meeting.

"We have shown that we can deploy the valve, that the valve functions; and we have one patient who is gradually improving, so I believe that the principle is now there as long as we can find the patients" best suited to TMVR, Dr. Thomas said.

"Patient selection is everything," he noted. The selection process is "perhaps more difficult than for transcatheter aortic valve replacement." Patients with severe mitral valve regurgitation often have substantial comorbidities such as left ventricular dysfunction, pulmonary disease, and renal disease, and these may mean a much longer delay to see patient improvement following TMVR compared with after an aortic valve is replaced, he noted.

Mitchel L. Zoler/Frontline Medical News

"Valve replacement seeks to eliminate mitral regurgitation, while clip systems attempt to reduce regurgitation by about one grade. We need to do both, and the difficulty will be determining which patients should get what treatment," Dr. Thomas said in an interview. "Perhaps the highest-risk patients should undergo repair" with a clip, he suggested.

"We need to select patients who will survive the [TMVR] procedure and get through the following 3 months because we may not see any benefit for 3-6 months, in contrast to aortic valve patients who recover and improve very quickly. I believe we will develop a complex algorithm based on each patient’s anatomy that will address the procedure’s risk and its potential to eliminate mitral regurgitation. The mitral clip is a relatively safe procedure, so it will be a much more complex algorithm than for the aortic valve."

A second report at the meeting reviewed experience with the first two patients who received the Tiara TMVR system, both at St. Paul’s Hospital in Vancouver, B.C. Like the Fortis valve, the Tiara is delivered by a transapical approach. The Tiara system delivers a mitral valve via a 32F catheter; the size of the Fortis catheter has not been reported, but a spokeswoman for Edwards acknowledged that it was a similarly large catheter and that efforts are ongoing to try to cut the catheter size. The Fortis mitral valve is 29 mm in diameter, while the size of the Tiara valve has not been reported. Procedure times for the two Tiara cases were 20 minutes for the first patient and 12 minutes for the second, reported Dr. Anson W. Cheung, surgical director of cardiac transplantation at St. Paul’s. The Fortis valve cases showed a learning curve similar to that of the Tiara cases, with the Fortis procedure time falling from 93 minutes for the first patient to 34 minutes for the fourth.

"The key is to catch patients before their left ventricle burns out, and to prevent the vicious cycle of high afterloading" that can occur when the mitral valve is replaced, Dr. Cheung said. He reported that his two cases had no complications or left ventricular outflow tract obstruction, and that one patient has now survived more than 3 months and has shown improved heart function and a halving of her baseline blood level of brain natriuretic peptide.

Mitchel L. Zoler/Frontline Medical News

"In patients with aortic stenosis, when you remove the obstructed [aortic] valve, they improve. In patients with mitral regurgitation, who develop very severely depressed left ventricular function, once you correct the regurgitation it increases stress on the ventricle and they can get into trouble," commented Dr. William Wijns, codirector of the Cardiovascular Center in Aalst, Belgium. "The complexity of the mitral valve problem is several orders of magnitude greater than with transcatheter aortic valve replacement," Dr. Wijns said.

Dr. Thomas has been a consultant to and has received research support from Edwards, the company developing the Fortis valve. Mr. Bapat has been a consultant to Edwards, Medtronic, and St. Jude and has received research support from Edwards. Dr. Cheung has been a consultant to and received honoraria from Neovasc, the company developing the Tiara valve. Dr. Wijns has received grant support to his institution from Edwards and 15 other companies, and he owns stock in two health care companies and a biotechnology company.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – Transcatheter mitral valve replacement finally took off this year, but it may keep a low profile short-term as investigators gain more clinical experience with transcatheter systems and slowly start to define the right types of patients for this procedure.

Transcatheter mitral valve replacement (TMVR) had something of a false start 2 years ago when CardiAQ announced the first clinical case of a patient with severe mitral valve regurgitation who underwent valve replacement using a transcatheter system at the Heart Centre of Rigshospitalet University Hospital, Copenhagen. Further details of that first case have not yet been reported. It was not until this past May that a second patient underwent TMVR performed by the same Danish team, using a second-generation CardiAQ system.

Mitchel L. Zoler/Frontline Medical News

Also this year came reports on two new TMVR systems, each used for the first time clinically, with five patients treated with the Fortis system made by Edwards Lifesciences, and two treated with the Tiara system made by Neovasc.

"We are finally on the journey of assessment of multiple transcatheter mitral valves. We’ve been saying that for a number of years, but it seems like now we truly will see progress in the mitral space," Dr. Martyn Thomas said during a talk at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

At the meeting, Dr. Thomas, an interventional cardiologist at St. Thomas’ Hospital, London, and his associate Vinayak Bapat, a cardiac surgeon, reported the experience with five patients treated with the Fortis valve system, including three patients treated by them and their colleagues in London, one patient in Bern, Switzerland, and a fifth who had been treated in Toronto just 4 days before their report at the meeting.

"We have shown that we can deploy the valve, that the valve functions; and we have one patient who is gradually improving, so I believe that the principle is now there as long as we can find the patients" best suited to TMVR, Dr. Thomas said.

"Patient selection is everything," he noted. The selection process is "perhaps more difficult than for transcatheter aortic valve replacement." Patients with severe mitral valve regurgitation often have substantial comorbidities such as left ventricular dysfunction, pulmonary disease, and renal disease, and these may mean a much longer delay to see patient improvement following TMVR compared with after an aortic valve is replaced, he noted.

Mitchel L. Zoler/Frontline Medical News

"Valve replacement seeks to eliminate mitral regurgitation, while clip systems attempt to reduce regurgitation by about one grade. We need to do both, and the difficulty will be determining which patients should get what treatment," Dr. Thomas said in an interview. "Perhaps the highest-risk patients should undergo repair" with a clip, he suggested.

"We need to select patients who will survive the [TMVR] procedure and get through the following 3 months because we may not see any benefit for 3-6 months, in contrast to aortic valve patients who recover and improve very quickly. I believe we will develop a complex algorithm based on each patient’s anatomy that will address the procedure’s risk and its potential to eliminate mitral regurgitation. The mitral clip is a relatively safe procedure, so it will be a much more complex algorithm than for the aortic valve."

A second report at the meeting reviewed experience with the first two patients who received the Tiara TMVR system, both at St. Paul’s Hospital in Vancouver, B.C. Like the Fortis valve, the Tiara is delivered by a transapical approach. The Tiara system delivers a mitral valve via a 32F catheter; the size of the Fortis catheter has not been reported, but a spokeswoman for Edwards acknowledged that it was a similarly large catheter and that efforts are ongoing to try to cut the catheter size. The Fortis mitral valve is 29 mm in diameter, while the size of the Tiara valve has not been reported. Procedure times for the two Tiara cases were 20 minutes for the first patient and 12 minutes for the second, reported Dr. Anson W. Cheung, surgical director of cardiac transplantation at St. Paul’s. The Fortis valve cases showed a learning curve similar to that of the Tiara cases, with the Fortis procedure time falling from 93 minutes for the first patient to 34 minutes for the fourth.

"The key is to catch patients before their left ventricle burns out, and to prevent the vicious cycle of high afterloading" that can occur when the mitral valve is replaced, Dr. Cheung said. He reported that his two cases had no complications or left ventricular outflow tract obstruction, and that one patient has now survived more than 3 months and has shown improved heart function and a halving of her baseline blood level of brain natriuretic peptide.

Mitchel L. Zoler/Frontline Medical News

"In patients with aortic stenosis, when you remove the obstructed [aortic] valve, they improve. In patients with mitral regurgitation, who develop very severely depressed left ventricular function, once you correct the regurgitation it increases stress on the ventricle and they can get into trouble," commented Dr. William Wijns, codirector of the Cardiovascular Center in Aalst, Belgium. "The complexity of the mitral valve problem is several orders of magnitude greater than with transcatheter aortic valve replacement," Dr. Wijns said.

Dr. Thomas has been a consultant to and has received research support from Edwards, the company developing the Fortis valve. Mr. Bapat has been a consultant to Edwards, Medtronic, and St. Jude and has received research support from Edwards. Dr. Cheung has been a consultant to and received honoraria from Neovasc, the company developing the Tiara valve. Dr. Wijns has received grant support to his institution from Edwards and 15 other companies, and he owns stock in two health care companies and a biotechnology company.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – A central problem with the SYMPLICITY HTN-3 trial of renal denervation was that the operators were inexperienced with the denervation procedure – and thus a majority of the renal denervations they carried out were not properly performed and left intact too many of the nerves that surround the renal arteries, commented Dr. Richard R. Heuser during the annual congress of the European Association of Percutaneous Cardiovascular Intervention.

"If you don’t get to the nerves and denervate them, you’re not going to have an effect," said Dr. Heuser, professor of medicine at the University of Arizona and chief of cardiology at St. Luke’s Medical Center in Phoenix.

Another limitation of the SYMPLICITY HTN-3 trial (N. Engl. J. Med. 2014;370:1393-1401) was that 25% of its enrolled patients were African Americans, and the trial’s results suggest that this patient subgroup does not respond to renal denervation with a significant fall in blood pressure.

In a video interview at the meeting, Dr. Heuser discussed the trial's potential limitations and renal denervation’s post-SYMPLICITY future.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – A central problem with the SYMPLICITY HTN-3 trial of renal denervation was that the operators were inexperienced with the denervation procedure – and thus a majority of the renal denervations they carried out were not properly performed and left intact too many of the nerves that surround the renal arteries, commented Dr. Richard R. Heuser during the annual congress of the European Association of Percutaneous Cardiovascular Intervention.

"If you don’t get to the nerves and denervate them, you’re not going to have an effect," said Dr. Heuser, professor of medicine at the University of Arizona and chief of cardiology at St. Luke’s Medical Center in Phoenix.

Another limitation of the SYMPLICITY HTN-3 trial (N. Engl. J. Med. 2014;370:1393-1401) was that 25% of its enrolled patients were African Americans, and the trial’s results suggest that this patient subgroup does not respond to renal denervation with a significant fall in blood pressure.

In a video interview at the meeting, Dr. Heuser discussed the trial's potential limitations and renal denervation’s post-SYMPLICITY future.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PARIS – A central problem with the SYMPLICITY HTN-3 trial of renal denervation was that the operators were inexperienced with the denervation procedure – and thus a majority of the renal denervations they carried out were not properly performed and left intact too many of the nerves that surround the renal arteries, commented Dr. Richard R. Heuser during the annual congress of the European Association of Percutaneous Cardiovascular Intervention.

"If you don’t get to the nerves and denervate them, you’re not going to have an effect," said Dr. Heuser, professor of medicine at the University of Arizona and chief of cardiology at St. Luke’s Medical Center in Phoenix.

Another limitation of the SYMPLICITY HTN-3 trial (N. Engl. J. Med. 2014;370:1393-1401) was that 25% of its enrolled patients were African Americans, and the trial’s results suggest that this patient subgroup does not respond to renal denervation with a significant fall in blood pressure.

In a video interview at the meeting, Dr. Heuser discussed the trial's potential limitations and renal denervation’s post-SYMPLICITY future.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler