Interventional Cardiology Research Reviewtm

Interventional Cardiology Research ReviewTM

Making Education Easy Issue 27 - 2019

In this issue: Welcome to issue 27 of Interventional Cardiology Research Review. We are please to return with a new issue, beginning with a paper reporting on the development and validation of >>Scoring chronic total coronary a contemporary scoring system for predicting outcomes following chronic total coronary occlusion angioplasty. occlusion angioplasty success A first-in-human comparison reported similar angiographic outcomes for a novel sirolimus-coated balloon that has a crystalline coating versus a clinically proven paclitaxel-coated balloon for the treatment of coronary >>Vancouver 3M clinical pathway for DES (drug-eluting stent) in-stent restenosis. We also report noninferiority of a sirolimus-eluting stent with a next-day discharge home after TAVR biodegradable polymer coating and ultra-thin struts when compared with the standard-of-care XIENCE stent in an all-comers trial of coronary artery stenosis. This issue concludes with a comparison of patency rates associated >>Sirolimus- vs. paclitaxel-coated with DES versus DCB (drug-coated balloon) angioplasty plus bailout stenting in patients with femoropopliteal balloon for coronary DES restenosis arterial disease. Long-term survival following multivessel I hope you find this update of interventional cardiology research informative and helpful in your everyday practice. >> We welcome any feedback and comments. revascularisation in diabetics Kind Regards, >>New trans-septal system for Associate Professor Craig Juergens percutaneous TMVR [email protected] >>Percutaneous repair vs. medical treatment for secondary mitral Derivation and validation of a chronic total coronary occlusion intervention regurgitation procedural success score from the 20,000-patient EuroCTO Registry >>Transcatheter mitral-valve repair in HF Authors: Szijgyarto Z et al. Sirolimus-eluting stent with ultra-thin Summary: These researchers used data from the EuroCTO registry to develop a contemporary scoring system >> (CASTLE) for predicting outcomes following chronic total coronary occlusion angioplasty. The respective failure strut for atherosclerotic lesions rates in the derivation (n=14,882) and validation (n=5745) cohorts were 15.5% and 12.2%. A total of 20.2% of >>TAVR with next-generation cases were performed retrogradely, and 9.3% underwent dissection re-entry. Six predictors of technical failure self-expanding devices were included in the CASTLE score, namely prior CABG, age ≥70 years, stump anatomy (blunt or invisible), degree of tortuosity (severe or unseen), occlusion length ≥20mm and severe extent of calcification, with each >>DES vs. DCB revascularisation for assigned a value of 1. The technical failure rate increased from 8% for CASTLE scores 0–1 to 35% for scores femoropopliteal arterial disease ≥4. The respective area under the curve values in the derivation and validation cohorts were 0.66 and 0.68. Chronic total occlusions are found in up to 20% of coronary angiograms and represent a Abbreviations used in this issue: Comment: therapeutic challenge, although PCI success rates have improved markedly with new techniques, equipment CABG = coronary artery bypass graft; DAPT = dual antiplatelet therapy; and approaches. However, success rates are lower than with conventional PCI and there have been a number DCB = drug-coated balloon; DES = drug-eluting stent; HF = heart failure; MI = myocardial infarction; PCI = percutaneous coronary intervention; of attempts to identify a reliable preassessment tool (e.g. J-CTO score) to gauge the likelihood of success. TAVR/TMVR = transcatheter aortic/mitral valve replacement; This study analysed data from the EuroCTO registry to derive the CASTLE score. The researchers have TCO = total coronary occlusion. developed a potentially useful tool identifying previous CABG, age ≥70 years, blunt stump anatomy, severe or unseen tortuosity, severe calcification and occlusion length ≥20mm as predictors of reduced success. Claim CPD/CME points Click here for more info. The score was more predictive than the J-CTO score, and it is unique in that it is derived from a very large dataset including numerous operators and institutions in a contemporary period. Follow RESEARCH REVIEW Australia on Twitter now @ Cardioreviews Reference: JACC Cardiovasc Interv 2019;12:335–42 https://twitter.com/cardioreviews Abstract

Before prescribing please review PBS and Product Information available in the primary advertisement in this publication or on request from NEW AstraZeneca on 1800 805 342 or www.astrazeneca.com.au/PI. orodispersible Reference: 1. Brilinta Approved Product Information. AstraZeneca Pty. Ltd. ABN 54 009 682 311. 66 Talavera Road, Macquarie Park, NSW 2113. www.astrazeneca.com.au. For Medical Information enquiries: 1800 805 342 or [email protected]. tablet To report an adverse event: 1800 805 342 or via https://aereporting.astrazeneca.com. AU-5909, WL301868, May 2019.

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The Vancouver 3M (Multidisciplinary, Multimodality, But Minimalist) clinical pathway facilitates safe next-day discharge home at low-, medium-, and high-volume transfemoral transcatheter aortic valve replacement centers Authors: Wood DA et al. Summary: The safety and efficacy of next-day discharge using the Vancouver 3M (Multidisciplinary, Multimodality, but Minimalist) clinical pathway was evaluated in 411 patients who underwent TAVR at six low-volume, four medium-volume and three high-volume centres; 58.2% received a SAPIEN XT valve and 41.8% received a SAPIEN 3 valve. The participants’ median age was 84 years and their median STS score was 4.9%. The respective next-day and 48-hour discharge rates were 80.1% and 89.5%. The composite primary endpoint of all-cause mortality or stroke ® by 30 days was recorded for 2.9% of the participants, with neither component significantly affected by hospital TAVR volume. Over 30 days, the major vascular BRILINTA ODT MAKES complication rate was 2.4%, the readmission rate was 9.2%, the cardiac readmission rate was 5.7%, the proportion needing new permanent pacemakers was 5.7% and the mild or greater paravalvular regurgitation rate was 3.8%. ACS LOADING QUICK * Comment: Transfemoral TAVR has become an excellent alternative to surgery in an ever-increasing range of patients. As the technique matures, there is an AND EASY increasing focus on expediting discharge using a so-called minimalist approach, although there is a need to assess the efficacy, safety and feasibility of a next-day discharge approach. This study evaluated an approach prospectively *rapidly disperses with saliva enrolling patients from 13 centres in North America performing varying volumes and low pill burden at loading of procedures. They included a large percentage of patients (55% of those screened), although there were a number of exclusions including poor social support, poor English comprehension, unfavourable vascular access and objective frailty measures. Procedures were mostly done with minimal or no procedural sedation and a minimum of invasive lines. Next-day discharge was achieved in 80% of patients with acceptable safety and efficacy outcomes. Further studies in other centres and assessing the cost effectiveness of this strategy are warranted, but this study provides a useful template for those centres wishing to adopt this approach.

Reference: JACC Cardiovasc Interv 2019;12:459–69 Abstract

Treatment of coronary drug-eluting stent restenosis by a sirolimus- or paclitaxel-coated balloon Authors: Ali RM et al. Summary: Fifty patients with DES coronary in-stent restenosis were randomised to a novel sirolimus-coated balloon 4 μg/mm2 or a paclitaxel-coated balloon 3 μg/mm2 in this trial. There was no significant difference between the sirolimus- versus 90mg Orodispersible tablets paclitaxel-coated balloon arms for in-segment late lumen loss on angiography at 6 months (primary endpoint; 0.17 vs. 0.21mm) or for other clinical events Only available in hospital (including stent thrombosis, cardiac-related mortality, target-lesion MI, target lesion revascularisation and binary restenosis) out to 12 months in a per-protocol analysis. Comment: Restenosis after DES implantation remains an ongoing issue with Before prescribing please review PBS treatment, with another DES or a paclitaxel-coated drug-eluting balloon a reasonable option. Whilst ‘limus’-eluting stents dominate the market, there has and Product Information available in the been no suitable ‘limus’-eluting DCB to date. This is explained by the need for primary advertisement in this publication or on sirolimus to be released for a period of weeks to effectively inhibit neointimal proliferation due to its reversible binding to FKBP-12. The crystalline coating request from AstraZeneca on 1800 805 342 (butylated hydroxytoluene) investigated in the present study showed excellent drug transfer rates and tissue persistence in a porcine coronary model, or www.astrazeneca.com.au/PI. which may explain the excellent results when compared with the market leading Reference: 1. Brilinta Approved Product Information. AstraZeneca Pty. Ltd. ABN 54 paclitaxel-coated balloon. This is a small study with a surrogate endpoint and more 009 682 311. 66 Talavera Road, Macquarie Park, NSW 2113. www.astrazeneca. studies should be done powered for clinical endpoints before this drug-eluting com.au. For Medical Information enquiries: 1800 805 342 or medinfo.australia@ balloon becomes part of our armamentarium. astrazeneca.com. To report an adverse event: 1800 805 342 or via https:// aereporting.astrazeneca.com. AU-5909, WL301868, May 2019. Reference: JACC Cardiovasc Interv 2019;12:558–66 Abstract

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Long-term survival following multivessel Percutaneous repair or medical treatment for revascularization in patients with diabetes secondary mitral regurgitation Authors: Farkouh ME et al. Authors: Obadia J-F et al., for the MITRA-FR Investigators Summary: The FREEDOM trial randomised 1900 patients with diabetes mellitus Summary: The MITRA-FR trial investigated the benefits of percutaneous mitral and multivessel coronary disease to undergo PCI with DESs (sirolimus- or paclitaxel- valve repair in patients with chronic HF and secondary mitral regurgitation. The study eluting) or CABG, along with optimal medical therapy, after which 943 entered the participants were randomised 1:1 to receive medical therapy alone with (n=152) FREEDOM Follow-On study with median follow-up of 7.5 years. There were 204 or without (n=152) percutaneous mitral valve repair. No significant difference was deaths recorded during the original FREEDOM trial and 110 during FREEDOM seen between the percutaneous mitral valve repair and medical therapy alone arms Follow-On. Compared with participants who underwent CABG, PCI-DES recipients for the proportion of participants with a primary outcome event (composite of death had a significantly higher all-cause mortality rate (24.3% vs. 18.3%; hazard ratio from any cause or unplanned hospitalisation for HF; 54.6% vs. 51.3%; odds ratio 1.36 [95% CI 1.07–1.74]), with a trend for a higher rate during FREEDOM Follow-On 1.16 [95% CI 0.73–1.84]) or for either of its components. (23.7% vs. 18.7%; 1.32 [0.97–1.78]). Comment: Patients with severe secondary mitral regurgitation (functional mitral Comment: The FREEDOM trial showed that CABG was a superior treatment regurgitation) have a poor outcome in the setting of HF. It is unclear whether it strategy than PCI with DESs in patients with multivessel coronary disease and a is a consequence or cause of the poor outcome. This multicentre, randomised, history of diabetes mellitus. The original study had median follow-up of 3.8 years open-label trial (MITRA-FR; 37 centres in France) of 304 patients attempted to and longer-term follow-up is of interest. Follow up beyond 5 years is unusual determine if repair of the valve using the MitraClip (Abbott vascular) improved in most trials, and this study presents follow-up at a median of 7.5 years in the prognosis compared with medical therapy. The technical success of the MitraClip 25 centres (of the original 140) that agreed to continue to collect long-term data. was reasonable with 76.4% of patients having mitral regurgitation grade 0+ to 1+ There were some baseline differences of patients with extended follow-up versus at discharge, although 14.6% of patients suffered a periprocedural complication those without, but there were no significant differences between the CABG and of device implantation. Unfortunately, percutaneous repair of the valve failed PCI groups. The benefits of surgery persisted including a reduction in long-term to reduce the composite endpoint when compared with medical therapy alone. mortality. Whilst there have been advances in medical therapy, PCI technology Mortality was 24.3% with the device versus 22.4% in the control group at and CABG techniques since the trial began enrolment in April 2005, the benefits 12 months. of surgery are impressive and should be presented to diabetic patients when discussing treatment options. Reference: N Engl J Med 2018;379:2297–306 Abstract Reference: J Am Coll Cardiol 2019;73:629–38 Abstract Interventional Cardiology Percutaneous transcatheter mitral valve replacement: TM first-in-human experience with a new transseptal system Research Review Authors: Webb JG et al. Summary: The feasibility of a percutaneous trans-septal TMVR system was Independent commentary by Associate Professor Craig Juergens evaluated in ten patients with severe symptomatic mitral regurgitation of degenerative Associate Professor Craig Juergens is an Interventional Cardiologist at Liverpool (n=4), functional (n=4) or mixed (n=2) aetiology and high surgical risk. Hospital where he is Head of Cardiology. He established the coronary The implantation success and technical success (primary endpoint) rates interventional service at Liverpool hospital which has subsequently become were both 90%. All implanted participants achieved total mitral regurgitation a centre of training for interventional Cardiologists. Apart from his interest in reductions to trivial or less, and their mean transmitral gradient was 2.3mm Hg. Interventional Cardiology, he has a major interest in acute coronary syndromes One participant did not have the device implanted due to pericardial effusion and has been involved in a large number of multicentre, multinational clinical requiring pericardiocentesis. The median hospitalisation duration was 1.5 days. trials. He has been author of over 80 peer reviewed papers and he continues No strokes, MIs, rehospitalisations, left ventricular outflow tract obstructions, device as an active clinician in the Department of Cardiology at Liverpool Hospital, migrations, emboli or conversions to mitral surgery were recorded over 30 days as well as providing support for the interventional Cardiology programme at and there were no deaths. One patient experienced recurrent regurgitation due to Orange Base hospital. paravalvular leak, which was treated with a closure device. All other treated patients experienced ≤1 mitral regurgitation.

Comment: Symptomatic mitral regurgitation conveys significant mortality and morbidity; however, many patients are not treated with surgical mitral Kindly Supported by regurgitation due to comorbidities. Whilst there have been some advancements with transcatheter repair, there is a need for TMVR. This study presents the first-in-human experience of a percutaneous trans-septal TMVR (Edwards Sapien M3). The ten patients included were deemed to be at high or prohibitive surgical risk by two experienced cardiac surgeons. Via a trans-septal approach, a balloon expandable valve is deployed within a nitinol dock that encircles the chordae tendineae and native mitral valve leaflets. The valve was successfully placed in nine patients with one developing a pericardial effusion requiring drainage and the procedure to be terminated. Results were good, although another patient Cardiology developed severe perivalvular leak by 30 days treated with a closure device. This is a single-centre study with short-term follow-up and more research is Research Review TM needed, but the early results are encouraging. SUBSCRIBE free, click here to visit www.researchreview.com.au Reference: J Am Coll Cardiol 2019;73:1239–46 and update your subscription to receive Cardiology Research Review. Abstract

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Transcatheter mitral-valve repair in patients with heart failure Authors: Stone GW et al., for the COAPT Investigators Summary: The COAPT study investigated the efficacy of transcatheter mitral valve repair in 614 patients with HF and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. The participants were randomised to receive medical therapy with (n=302) or without (n=312) transcatheter mitral valve repair. The annualised rate of all hospitalisations for HF within 24 months (primary efficacy endpoint) was significantly lower in the device group compared with the control group (35.8% vs. 67.9% per patient-year; hazard ratio 0.53 [95% CI 0.40–0.70]), as was ® the 24-month all-cause mortality rate (29.1% vs. 46.1%; 0.62 [0.46–0.82]). The 12-month freedom from device-related complications rate (primary safety endpoint) BRILINTA ODT was 96.6%, significantly greater than the prespecified objective performance goal of 88.0% (p<0.001).

Comment: This randomised trial (COAPT) performed in 78 sites in North America compared the MitraClip with optimal medical therapy in 614 patients with moderate-to-severe or severe secondary mitral regurgitation. The clip was successfully implanted in 98% of patients and the degree of mitral regurgitation achieved was 1+ or lower in 82% at hospital discharge. There was a dramatic reduction in death from any cause at 2 years favouring the device group (29.1% Rapidly disperses Low pill burden vs. 46.1% [p<0.001]). Potential reasons for the dramatically different outcome to the French study published in the same issue of the N Engl J Med may be that with saliva (with or at loading 1 these patients were more likely to be truly refractory to optimal HF treatment, without water) when (2 tablets only ) the baseline mitral regurgitation may have been worse and the intervention may placed on the tongue*1 have been superior with more clips used and less mitral regurgitation at follow- up. It seems there is a role for the device for those patients truly refractory to optimal medical therapy. *Bioequivalent to Brilinta film-coated Reference: N Engl J Med 2018;379:2307–18 1 Abstract whole tablets. Brilinta provides faster and more consistent inhibition of Safety and efficacy of a sirolimus-eluting coronary platelet aggregation than clopidogrel1,2 stent with ultra-thin strut for treatment of atherosclerotic lesions (TALENT) Authors: Zaman A et al., on behalf of the TALENT trial investigators STREAMLINED AUTHORITY CODE 5746 Summary: Adult patients with ≥1 coronary artery stenosis of >50% in a native coronary artery, saphenous venous graft or arterial bypass conduit, and with PBS Information: Film-coated tablet. Authority a reference vessel diameter of 2.25–4.50mm, were randomised to PCI with ( ) implantation of either a sirolimus-eluting stent with a biodegradable polymer Required STREAMLINED . Treatment of acute coating and ultrathin struts (Supraflex) or an everolimus-eluting stent with a durable coronary syndrome (myocardial infarction or unstable polymer coating (XIENCE) in this noninferiority trial; 720 and 715 participants from angina) in combination with aspirin. Orodispersible the respective arms underwent index procedures. The respective proportions of tablet. This product is not listed on the PBS. the everolimus- and sirolimus-eluting stent groups who met the 12-month primary endpoint of cardiac-related death, target-vessel MI or clinically indicated target lesion revascularisation were 4.9% and 5.3% (p<0.0001 for noninferiority). The prevalence of definite or probable stent thrombosis was low in both study groups with no Please CLICK HERE to review full significant between-group difference. Product Information before prescribing. Comment: This 1435-patient, prospective, randomised, single-blind, multicentre Further information available on request study across 23 centres in Europe compared the Supraflex (Sahajanand Medical Technologies, India) with XIENCE (Abbot Vascular, USA) stent. The Supraflex from AstraZeneca on 1800 805 342 stent is a sirolimus-eluting, ultrathin (60µm) cobalt-chromium alloy platform with a biodegradable polymer. There were few inclusion and exclusion criteria, or www.astrazeneca.com.au/PI. and patients with stable coronary disease were recommended to continue Reference: 1. Brilinta Approved Product Information. 2. Gurbel PA et al. Circulation DAPT for 6 months whilst patients with an acute coronary syndrome were 2009;120:2577-2585. BRILINTA® is a registered trademark of the AstraZeneca group of recommended to have 12 months of DAPT. There was a higher device success companies. Registered user AstraZeneca Pty. Ltd. ABN 54 009 682 311. 66 Talavera Road, rate with XIENCE (99.5%) versus the Supraflex (97.6%), which may reflect lack Macquarie Park, NSW 2113. www.astrazeneca.com.au. For Medical Information enquiries: of operator familiarity with the new device. The stent was found to be noninferior 1800 805 342 or [email protected]. To report an adverse event: 1800 to XIENCE with a low rate of definite or probable stent thrombosis (0.8%) in both 805 342 or via https://aereporting.astrazeneca.com. AU-5909, WL301868, May 2019. groups at 12 months. This stent therefore may be a reasonable alternative to the industry leader XIENCE in our cath labs.

Reference: Lancet 2019;393:987–97 Abstract

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Transcatheter aortic valve replacement with Drug-eluting stent versus drug-coated balloon next-generation self-expanding devices revascularization in patients with femoropopliteal Authors: Pagnesi M et al. arterial disease Summary: The ACURATE neo and Evolut PRO devices for TAVR were compared in a Authors: Bausback Y et al. retrospective cohort of patients with a mean STS score of 5.1%. From 1263 patients Summary: Patients with symptomatic femoropopliteal disease (n=150) were in whom ACURATE neo devices were used and 288 in whom Evolut PRO devices were stratified by lesion length and randomised to primary DES implantation or DCB used, 251 propensity matched pairs were identified for comparison. No significant angioplasty with bailout stenting in this trial; more than half the lesions were difference was seen between use of the ACURATE neo and Evolut PRO devices for total occlusions, and the stenting rate was 25.3% among the DCB recipients. the VARC (Valve Academic Research Consortium)-2 device success rates (90.6% vs. No significant difference was seen between the DES and DCB arms for Kaplan-Meier 91.6% [p=0.751]), predischarge moderate-to-severe paravalvular aortic regurgitation estimates of primary patency at 12 months (79% vs. 80% [p=0.96]); these rates (7.3% vs. 5.7% [p=0.584]) or 30-day clinical outcomes including all-cause mortality had decreased at 36 months (54% vs. 38% [p=0.17]). The 12-month freedom from (3.2% vs. 1.2% [p=0.221]), stroke (2.4% vs. 2.8% [p=1.000]), new permanent clinically driven target lesion revascularisation rate was >90%, falling to ~70% at pacemaker implantation (11.0% vs. 12.8% [p=0.565]) and the VARC-2 early safety 36 months in both groups. The overall 36-month mortality rate was 7.3%, including endpoint (10.6% vs. 10.4% [p=1.000]). Consistent findings were seen for the overall one procedure-related death in the DCB arm. Clinical outcomes remained improved unmatched cohort in logistic regression analyses. out to 36 months.

Comment: TAVR has revolutionised the treatment of severe aortic stenosis and Comment: The superficial common femoral artery is commonly affected by the technology of the valves continues to evolve. It is important to evaluate these symptomatic peripheral arterial disease. Treatment with balloon angioplasty is new valves to ensure new iterations remain efficacious and meet the promise associated with high restenosis rates and is inferior to DES and DCB technologies, of reducing complications. This study compared the ACURATE neo (Boston but to date there have been no randomised trials comparing these newer Scientific) with the latest generation Evolut PRO (Medtronic) self-expanding technologies. The current trial addresses this shortfall in a five-centre trial valves in the context of a propensity-matched multicentre registry. The rate of performed in Germany and Belgium, comparing the commercially available moderate-to-severe paravalvular aortic regurgitation was acceptable (5.3%) and self-expanding Zilver (Cook) DES with a paclitaxel DCB (Medtronic). Bailout stenting similar between groups. In the overall population, there was more permanent was needed in 25% of patients in the DCB arm. Patency rates were similar at pacemaker implantation (13.2% vs. 8.8%) in the Evolut PRO group and higher 12 months, but there was a trend in favour of DESs at 36 months, particularly bleeding rates in the ACURATE neo group, but these differences disappeared in lesions longer than 10cm. Larger studies powered for clinical endpoints are after propensity adjustment. Both valves performed well at 30 days with needed to further define the role of these technologies. similar outcomes with each device. Future prospective randomised trials are needed with long-term follow-up to see how these new valves compare with Reference: J Am Coll Cardiol 2019;73:667–79 balloon-expandable and older generation self-expanding valves. Abstract

Reference: JACC Cardiovasc Interv 2019;12:433–43 Abstract

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