Debra L. Beck 2017-02-03 00:43:46
Impacting Interventional Cardiology in 2017 There is great uncertainty in health care in North America these days and it’s likely to continue for most of 2017. Efforts to repeal parts of the Affordable Care Act are already underway, but timelines and alternatives are unclear at this time. Based on some of the Tweets from the new Trump administration, it’s a good guess that drug prices will be forced lower. Getting needed medications to patients is always a good thing, but will a frontal attack on the drug industry hamper medical research and biotech innovation or just hammer 401Ks? Confirmations of nominees to head key agencies like the U.S. Food and Drug Administration (FDA) are also underway, with some of the names proposed generating lively debate. With so much of the macroenvironment in play as this first issue of the new and improved Cardiology: Interventions goes to press, we sought a better sense of the narrower view of the interventional cardiology world. We asked Peter C. Block, MD, MACC, editor-in-chief of Cardiology: Interventions, and Spencer B. King III, MD, MACC, editor-in-chief of JACC: Cardiovascular Interventions to share their forecasts for interventional cardiology in 2017. In short, 2017 looks to be a solid, steady ahead kind of year for interventional cardiology. It’s not likely to serve up any major practice-changing breakthroughs, nor any big train wrecks, but a healthy number of new and improved procedures to keep catheterization (cath) lab schedules booked are likely. PROCEDURE VOLUMES UP! Interventional cardiology is booming, and not only because of demographic factors (an aging population and growing prevalence of obesity and diabetes). Multiple lines of research reported in 2016 lent support for the use of percutaneous options across an everincreasing number of patient populations. Here are just two: • RESPECT for patent foramen ovale (PFO) closure. The question of PFO closure efficacy has been a decades-long headache, but in final study findings, closure solidly beat medical management for secondary stroke prevention in the appropriately named RESPECT trial.1 As an added boost, the FDA approved the Amplatzer PFO Occluder (St. Jude Medical) in October 2016. The Amplatzer had been withdrawn from the U. S. market in 2006 after a humanitarian device exemption expired, but will now be re-released. PFO closure procedures are expected to pick up in 2017, but may do so even more if added clarity on the procedure comes from the Gore REDUCE trial, a test of the W.L. Gore & Associates HELEX Septal Occluder for PFO closure in stroke patients. Gore REDUCE is scheduled to release findings in early 2017.2 • PARTNER 2A for transcatheter aortic valve replacement (TAVR) in intermediate-risk patients: Despite a potential setback with durability (stay tuned for more details on this in 2017), TAVR continues its descent down to the low notes of the risk scale. PARTNER 2A confirmed the noninferiority of Sapien XT implantation to surgical aortic valve replacement (SAVR) in intermediate-risk patients with symptomatic severe aortic stenosis.3 In those suitable for transfemoral access, superiority was seen for the primary endpoint of all-cause death and disabling stroke at two years. If TAVR continues to supplant SAVR as the standard of care for all patients with severe aortic stenosis, the U. S. TAVR market could triple in size to about $3 billion annually.4 “The overall use of aortic valve intervention for aortic stenosis will continue to increase, and what we’ll see really soon is that TAVR will be competitive in the routine, low-risk aortic patients who need an intervention,” says King. But even as TAVR sports fast-growing evidence that will help fine tune technical and patient selection issues, the finding that some patients just don’t seem to benefit much from the procedure remains an important societal question that we will likely continue to grapple with in 2017. “There is no question that someone with severe aortic stenosis, no matter how frail or how much cancer or other comorbidities they have, is going to feel better after having the valve replaced,” says King. “The question is given its exorbitant cost and if it extends life for only a few months, or the patient feels better but can’t really do much more, is it worth doing?” Beyond the valves, positive findings for left atrial appendage closure in atrial fibrillation (AFib) may increase the number of clinicians and patients opting to skip the lifelong anticoagulation route. As well, new chronic total occlusion (CTO) technologies may affect an increase in interventionalists willing to attempt crossings. On his 2017 wish list, Block suggests that a coronary imaging technology for CTO interventions that allows visualization within the artery during the intervention would be very welcome. “We simply don’t have adequate visualization inside the arteries so we can work and see at the same time. I would love to see industry come up with something that would allow us, for example, to have an ultrasound or optical coherence tomography (OCT) or whatever wire that you can place right next to the wire you’re working with so you can see what you’re doing while you’re doing it.” Market analysis supports the contention that interventional cardiologists needn’t worry about their procedure numbers: the global market for interventional cardiovascular surgery devices is expected to grow from nearly $12.6 billion in 2015 to $21.2 billion in 2020, representing a compound annual growth rate of 11. 0 percent for the period 2015-2020.5 AN AUC BUMP TO PROCEDURAL LENGTH? Primary PCI procedures may take longer in 2017 because of some new multi-society guidance. Updated Appropriate Use Criteria for Coronary Revascularization in Acute Coronary Syndromes (ACS) were released on Dec. 14, 2016.6 (See article on page 32. ) The biggest news from this long-anticipated update to 2012 guidance is more leniency for treatment of non–infarct-related stenoses in patients with STEMI. The authors suggested that nonculprit lesions can be treated either during the primary PCI or in a staged procedure during the index hospitalization. “It’s quite nuanced,” says King. “The new guidance doesn’t say it’s better to treat multiple lesions, but it’s no longer out of bounds based on the operator’s judgment and the documentation of ischemia.” LITHOPLASTY GETS THE BLOOD FLOWING Asked if there are any new technologies that seem really promising, both Block and King say lithoplasty is the one that they are most excited about. Interestingly, though, they have differing ideas of how they’d like to see it utilized. Lithoplasty uses sound waves to disrupt vascular calcium. The Shockwave Medical Peripheral Lithoplasty System is CE marked and received FDA approval for the treatment of calcified peripheral arterial disease in September 2016. At TCT 2016, DISRUPT CAD, a pre-market, prospective, multicenter single arm trial of the Shockwave system in patients with complex calcified obstructive coronary artery disease prior to drugeluting stent implantation showed 98 percent device success, an acute gain of 1.7 mm, and 13 percent residual stenosis post procedure. An OCT substudy demonstrated that the treated calcium was fractured though all layers and around the circumference of the artery. “If this works in the coronaries, it will take away all the rotablating and various kinds of cutting balloons and rotational atherectomy that we have now,” says Block. “It will be more efficient and probably safer.” Going one step further, he suggested that this technology, if proven safe, could be a real boon for aortic valve intervention. “The extension of the concept to valvular heart disease would be an extraordinary step and might allow far better placement of transcatheter valves, for example, without some of the issues that heavy calcification of valves can produce when you’re trying to fix them,” he suggests. Indeed, the company has completed a feasibility study for the treatment of aortic stenosis with lithoplasty. King likes this idea too, but suggests that TAVR devices might need some design changes if they are to be used after lithoplasty, because they require a somewhat stiff aortic annulus to hold the valve in place. “If you soften it up too much, you might have an issue with securing the valve.” For his part, King sees lithoplasty and bioabsorbable vascular scaffolds having a “natural interdependence.” “If we get to the point where bioabsorbable vascular scaffolds become more mainline, then the need for preparing or tenderizing the artery with lithoplasty could be a critical component of implanting a bioabsorbable scaffold, which requires low pressure but complete expansion.” While exciting to ponder, these advances aren’t ready for prime time yet. The Shockwave system is still being tested in the coronary space and has yet to gain approval for a coronary indication. VALVE ADD-ONS The mitral valve is ready to stop playing second fiddle, percutaneously speaking, to the aortic valve. The need for effective and safe new treatments is clear: the prevalence of mitral valve disease is greater than that of aortic valve disease and more than half of patients with severe mitral regurgitation have comorbidities that preclude surgical treatment.7 “It turns out that valve replacement in the mitral position is a much more difficult problem than the aortic position,” says King. He thinks percutaneous mitral valve intervention will advance beyond the MitraClip in 2017, but that percutaneous mitral valve replacement is unlikely to become widely available anytime soon. Of course, just because it’s being widely studied doesn’t mean it’ll work. Block thinks this may be the case with the ongoing European outcome trials of transcatheter direct and indirect mitral valve annuloplasty, “which everybody is touting and saying they’re terrific.” For his part, he thinks they may not work as intended. “These annuloplasty devices are just replicas of what the surgeons did in the 1960s and 1970s and they all came apart. Suture-based annuloplasty never worked surgically, so the question is will it work percutaneously, and my thought is, ‘why should it?’” There are a handful of annuloplasty devices in development— including the Mitralign (Mitralign Inc.) and the Cardioband System (Valtech), both of which received CE Mark approval in the past two years. HOW ‘BOUT WE JUST CURE THIS THING! In 2014, King asked in an editorial whether PCSK9 inhibitors might be the “fluoride” of cardiology.8 The addition of fluoride to communal water supplies, started in the U. S. more than 70 years ago, is credited with a marked reduction in dental carries, a subsequently reduced need for dentists, and the closure of several dental schools. His question seems especially prescient given the recent results from the GLAGOV trial. Presented at AHA 2016, GLAGOV studied the addition of evolocumab (Repatha, Amgen) in statin-treated patients and found that treatment with the PCSK9 inhibitor was associated with dramatic reductions in LDL-C.9 After 18 months of treatment, mean LDL-C fell from a baseline of 92.5 mg/dl to 36.6 mg/dl. Better yet, the investigators found that PCSK9 treatment on top of statin therapy resulted in a significant reduction in intravascular ultrasound-measured percent atheroma volume (PAV) compared with statin monotherapy. Of note, 58 percent of patients entered the trial using high-dose statins. Plaque regression (defined as any change in PAV or total atheroma volume less than zero) was seen in 64. 3 percent of evolocumab-treated patients (p < 0.001 compared with statin-only patients). It has been suggested that PCSK9 inhibitors, should they be found to safely reduce cardiovascular events or stabilize vulnerable plaques, could be the biggest disrupter to interventional cardiology since, well, since the invention of over-the-wire balloon angioplasty. “Let’s say direct-to-consumer advertising doesn’t go away, which it’s not going to under the current free-for-all situation. If the PCSK9 outcome trials are positive and we have documented improvement in survival and plaque regression, somebody will make a TV ad about it and we’ll have patients coming in asking for these drugs all over the place,” suggests King. Going further with utter speculation…if President Trump indeed does the populist move and forces drug prices lower, including PCSK9 prices, could interventional cardiology meet their fluoride moment? “Things change,” says King. “The very nice hospital where I used to practice in Denver was established to treat tuberculosis … It’s hard to imagine medical therapy for atherosclerosis changing to such a dramatic degree, but if it did it would massively change the way cardiovascular care is delivered. It’ll take some years to play out, but we could see some big news this year References Thaler DE. RESPECT: final long-term outcomes from a prospective, randomized trial of PFO closure in patients with cryptogenic stroke. Presented at TCT 2016, Washington, DC. November 1, 2016. Gore REDUCE trial. Available at: clinicaltrials.gov/ct2/show/NCT00738894. Accessed January 19, 2017. Leon MB, Smith CR, Mack MJ, et al. N Engl J Med 2016;374:1609-20. Messenger S. A comprehensive guide to the U.S. TAVR market: surveying the field. Available at: www.meddeviceonline.com/ doc/a-comprehensive-guide-to-the-u-s-tavrmarket- surveying-the-field-0001. Accessed January 19, 2017. Joshi B. Cardiovascular surgical devices: technologies and global markets. Available at: www.bccresearch.com/market-research/ healthcare/cardiovascular-surgical-devicesmarkets- report-hlc076c.html. Accessed January 19, 2017. Coronary Revascularization Writing Group, Patel MR, Calhoon JH, Dehmer GJ, et al. J Am Coll Cardiol 2016;Dec 14:[Epub ahead of print]. Testa L, Latib A, Montone RA, Bedogni F. J Thorac Cardiovasc Surg 2016;152:319-27. King SB 3rd. JACC Cardiovasc Interv 2014;7:1331-2. Nicholls SJ, Puri R, Anderson T, et al. JAMA 2016;316:2373-84. IMPRESS Trial: Impella Fails to Demonstrate Superiority Over IABP Mortality in patients with acute myocardial infarction with cardiogenic shock remains high, despite ongoing advances in treatment.1-4 While the intra-aortic balloon pump (IABP) has been the most widely short-term mechanical circulatory support system in use for the past 5 decades,5 there is a need to improve patient outcomes either with new treatments or perhaps revised treatment protocols. To this end,can reduce 30-day mortality (in MI patients) in comparison with an IABP. They looked specifically at the Impella CP device (maximum output around 3.7 L/min). The multicenter, randomized study included patients presenting with acute MI with Stsegment elevation complicated by severe cardiogenic shock in the setting of percutaneous coronary intervention (PCI). Patients were randomized at 1:1 to receive either the Impella device (n = 24) or an IABP (n = 24). The primary study endpoint was 30-day all-cause mortality, with 6-month all-cause mortality set as a secondary endpoint. Trial Results The researchers reported no significant differences in all-cause mortality between the two patient groups (50% IABP vs. 46% Impella; p = 0. 92) at 30 days, as well as no significant differences at 6 months (50% IABP vs. 50% Impella; p = 0.923; see Figure 1). They also reported that refractory cardiogenic shock was the cause of death in 29% of deceased patients (25% in the IABP group vs. 33% in the Impella group). Subgroup analysis revealed “no significant interactions in 30-day mortality between the IABP and Impella patients” with respect to other factors such as age, sex, return of spontaneous circulation (ROSC), lactate levels upon admission, time of device placement, TIMI flow following the procedure, and traumatic injuries upon admission. Of note, when analyzing the combined study population, patients who had ROSC in less than 20 minutes had lower 30-day mortality (19% vs. 70% , p = 0.001), as well as in patients with admission levels of lactate < 7.5 mmol/L (29% vs. 60% , p = 0.04). One patient in each treatment group suffered ischemic stroke. A trend toward lower mortality was seen across the combined study groups if mechanical support was initiated prior to primary PCI (25% vs. 53%, p = 0.16), and also in patients without traumatic injuries due to cardiac arrest (44% vs. 71%, p = 0.18). The IMPRESS Severe Shock Trial is the largest study to compare the Impella device to IABP, and so far, the only trial to use the Impella CP device. The IMPRESS Severe Shock Trial is the largest study to compare the Impella device to IABP, and so far, the only trial to use the Impella CP device. Some Notable Data Points There were some findings of note within the study’s supplementary data. Major bleeding occurred more often in the Impella- treated patients than in the IABP-treated patients (33% vs. 8%; see Figure 2). This is in line with results from a registry comparing the two devices (in that study, it was 26% Impella vs. 6% IABP), and two other large, multicenter Impella registries describe bleeding rates requiring transfusion of 24.2% and 17.5%. Hemolysis rates in those registries were 7.5% and 10. 3% respectively.6 This study found hemolysis requiring device extraction only occurred in the Impella group and affected 8% of patients. Patients in the IABP group had a higher average pre-PCI Syntax score than those in the Impella group (28.2±10.6 vs. 23.2 ± 8.7). Five patients in the Impella group required rehospitalization. In addition, patients in the Impella group required an overall longer hospital stay than those in the IABP group (16 days vs. 10 days). The researchers also noted that the time that the device is implanted in relation to the PCI procedure could be associated with lower mortality rates. “Earlier reports have demonstrated a better survival in patients who received the Impella 2.5 before primary PCI than implantation post-PCI,”7 they wrote. “Our data also show a trend towards lower mortality rates in patients in whom the device is initiated before the primary PCI in both the Impella and IABP group.” The small patient population was cited by the authors as the study’s chief limitation. However, several randomized controlled trials (RCTs) have compared the Impella device with IABP, and although all trials were underpowered to adequately evaluate mortality, the pooled data from these trials illustrate a compelling story. There has been a total of 95 patients randomized between the 3 RCTs comparing Impella with IABP in cardiogenic shock after acute MI. A recently published meta-analysis found no difference in all-cause mortality between the patient groups at 30-days (relative risk (RR) 0.99; 95% CI, 0.62- 1. 58; p = 0.95) or at 6-months (RR 1.15; 95% CI, 0. 74-1.48; p = 0.53). There was also no difference in left ventricular ejection fraction (LVEF) between Impella- and IABP-treated patients during followup (mean difference: -2.6%; 95% CI, -9.1-3.8; p = 0. 42). Although improvement in hemodynamic support has been shown with Impella, this has not translated into improved clinical outcomes.8 ¦ References Hochman JS, Sleeper LA, Webb, JG, et al. N Engl J Med. 1999;341:625-34. Babaev A, Frederick PD, Pasta DJ, et al. JAMA. 2005;294:448-54. Goldberg RJ, Spencer FA, Gore JM, et al. Circulation. 2009;119:1211-9. Thiele H, Zeymer U, Neumann FJ, et al. N Engl J Med. 2012;367:1287-96. Stretch R, Sauer CM, Yuh DD, Bonde P, et al. J Am Coll Cardiol. 2014;64:1407-15. Ouweneel DM, Henriques JP. Heart. 2012;98:1246-54. O’Neill WW, Schreiber T, Wohns DH, et al. J Intv Cardiol. 2014;27:1-11. Ouweneel DM, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2016.10.026 Disclosures: The Academic Medical Center has received research grants and honoraria from Abiomed, Inc. The trial was funded by the Academic Medical Center, Amsterdam.
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