Below is an up to date list (15th April 2021) of all publications using BCIS / NICOR dataset. The first is PCI publications the second is TAVI publications

A huge thanks to Tim Kinnaird from University Hospital of Wales for preparing this list

TAVI PUBLICATIONS

1. Pre-procedural pacing bias among transcatheter aortic valves with higher post-procedure pacing rates: evidence from the UKTAVI  Hilling-Smith R, Smethurst J, Cockburn J, Williams T, Trivedi U, Banning A, Redwood S, de Belder A, MacCarthy P, Khogali S, Blackman D, Ludman P, Hildick-Smith D.Heart Vessels. 2021 Mar;36(3):408-413. doi: 10.1007/s00380-020-01703-z
2. Survival relative to pacemaker status after transcatheter aortic valve implantation. Myat A, Mouy F, Buckner L, Cockburn J, Baumbach A, MacCarthy P, Banning AP, Curzen N, Hilling-Smith R, Blackman DJ, Mullen M, de Belder M, Cox I, Kovac J, Manoharan G, Zaman A, Muir D, Smith D, Brecker S, Turner M, Khogali S, Malik IS, Alsanjari O, D’Auria F, Redwood S, Prendergast B, Trivedi U, Robinson D, Ludman P, de Belder A, Hildick-Smith D.Catheter Cardiovasc Interv. 2021 Jan 27. doi: 10.1002/ccd.29498
3. In-hospital stroke after transcatheter aortic valve implantation: A UK observational cohort analysis. Myat A, Buckner L, Mouy F, Cockburn J, Baumbach A, Banning AP, Blackman DJ, Curzen N, MacCarthy P, Mullen M, de Belder M, Cox I, Kovac J, Brecker S, Turner M, Khogali S, Malik IS, Alsanjari O, Redwood S, Prendergast B, Trivedi U, Robinson D, Ludman P, de Belder A, Hildick-Smith D.Catheter Cardiovasc Interv. 2021 Mar;97(4):E552-E559. doi: 10.1002/ccd.29157.
4. Transcatheter aortic valve implantation via surgical subclavian versus direct aortic access: A United Kingdom analysis. Myat A, Papachristofi O, Trivedi U, Bapat V, Young C, de Belder A, Cockburn J, Baumbach A, Banning AP, Blackman DJ, MacCarthy P, Mullen M, Muir DF, Nolan J, Zaman A, de Belder M, Cox I, Kovac J, Brecker S, Turner M, Khogali S, Malik I, Redwood S, Prendergast B, Ludman P, Sharples L, Hildick-Smith D.Int J Cardiol. 2020 Jun 1;308:67-72. doi: 10.1016/j.ijcard.2020.03.059.
5. UKTAVI  Ludman PF.Heart. 2019 Mar;105(Suppl 2):s2-s5. doi: 10.1136/heartjnl-2018-313510.PMID: 30846517 Review.
6. Long-Term Durability of Transcatheter Aortic Valve Prostheses. Blackman DJ, Saraf S, MacCarthy PA, Myat A, Anderson SG, Malkin CJ, Cunnington MS, Somers K, Brennan P, Manoharan G, Parker J, Aldalati O, Brecker SJ, Dowling C, Hoole SP, Dorman S, Mullen M, Kennon S, Jerrum M, Chandrala P, Roberts DH, Tay J, Doshi SN, Ludman PF, Fairbairn TA, Crowe J, Levy RD, Banning AP, Ruparelia N, Spence MS, Hildick-Smith D. J Am Coll Cardiol. 2019 Feb 12;73(5):537-545. doi: 10.1016/j.jacc.2018.10.078.
7. Association of comorbid burden with clinical outcomes after transcatheter aortic valve implantation. Bagur R, Martin GP, Nombela-Franco L, Doshi SN, George S, Toggweiler S, Sponga S, Cotton JM, Khogali SS, Ratib K, Kinnaird T, Anderson RA, Chu MWA, Kiaii B, Biagioni C, Schofield-Kelly L, Loretz L, Torracchi L, Sekar B, Kwok CS, Sperrin M, Ludman PF, Mamas MA. Heart. 2018 Dec;104(24):2058-2066. doi: 10.1136/heartjnl-2018-313356. Epub 2018 Jul 20.
8. Do frailty measures improve prediction of mortality and morbidity following transcatheter aortic valve implantation? An analysis of the UK TAVI registry. Martin GP, Sperrin M, Ludman PF, deBelder MA, Gunning M, Townend J, Redwood SR, Kadam UT, Buchan I, Mamas MA. BMJ Open. 2018 Jun 30;8(6):e022543. doi: 10.1136/bmjopen-2018-022543
9. Novel United Kingdom prognostic model for 30-day mortality following transcatheter aortic valve implantation. Martin GP, Sperrin M, Ludman PF, de Belder MA, Redwood SR, Townend JN, Gunning M, Moat NE, Banning AP, Buchan I, Mamas MA. Heart. 2018 Jul;104(13):1109-1116. doi: 10.1136/heartjnl-2017-312489. Epub 2017 Dec 7.
10. Relative Survival After Transcatheter Aortic Valve Implantation: How Do Patients Undergoing Transcatheter Aortic Valve Implantation Fare Relative to the General Population? Martin GP, Sperrin M, Hulme W, Ludman PF, de Belder MA, Toff WD, Alabas O, Moat NE, Doshi SN, Buchan I, Deanfield JE, Gale CP, Mamas MA; National Institute of Cardiovascular Outcomes Research (NICOR). J Am Heart Assoc. 2017 Oct 17;6(10). pii: e007229. doi: 10.1161/JAHA.117.007229.
11. United Kingdom: coronary and structural heart interventions from 2010 to 2015. Ludman PF, de Belder MA, Redwood S, Banning A. 2017 May 15;13(Z):Z83-Z88. doi: 10.4244/EIJ-D-16-00833.
12. Dialysis Following Transcatheter Aortic Valve Replacement: Risk Factors and Outcomes: An Analysis From the UK TAVI (Transcatheter Aortic Valve Implantation) Registry. Ferro CJ, Law JP, Doshi SN, de Belder M, Moat N, Mamas M, Hildick-Smith D, Ludman P, Townend JN; UK TAVI Steering Group and the National Institute for Cardiovascular Outcomes Research. JACC Cardiovasc Interv. 2017 Oct 23;10(20):2040-2047. doi: 10.1016/j.jcin.2017.05.020. Epub 2017 Aug
13. Pre-Implantation Balloon Aortic Valvuloplasty and Clinical Outcomes Following Transcatheter Aortic Valve Implantation: A Propensity Score Analysis of the UK Registry. Martin GP, Sperrin M, Bagur R, de Belder MA, Buchan I, Gunning M, Ludman PF, Mamas MA. J Am Heart Assoc. 2017 Feb 18;6(2). pii: e004695. doi: 10.1161/JAHA.116.004695.
14. Transcatheter Aortic Valve Replacement Using the Repositionable LOTUS Valve: United Kingdom Experience. Rampat R, Khawaja MZ, Byrne J, MacCarthy P, Blackman DJ, Krishnamurthy A, Gunarathne A, Kovac J, Banning A, Kharbanda R, Firoozi S, Brecker S, Redwood S, Bapat V, Mullen M, Aggarwal S, Manoharan G, Spence MS, Khogali S, Dooley M, Cockburn J, de Belder A, Trivedi U,Hildick-Smith D. JACC Cardiovasc Interv. 2016 Feb 22;9(4):367-372. doi: 10.1016/j.jcin.2015.12.012
15. Impact of left ventricular function and transaortic gradient on outcomes from transcatheter aortic valve implantation: data from the UK TAVI Registry. Malkin CJ, Long WR, Baxter PD, Gale CP, Wendler O, Monaghan M, Thomas MT, Ludman PF, de Belder MA, Cunningham AD, Moat NE, Blackman DJ; National Institute for Cardiovascular Outcomes Research (NICOR). EuroIntervention. 2016 Feb;11(10):1161-9. doi: 10.4244/EIJY14M12_12.
16. Activity and outcomes for aortic valve implantations performed in England and Wales since the introduction of transcatheter aortic valve implantation. Grant SW, Hickey GL, Ludman P, Moat N, Cunningham D, de Belder M, Blackman DJ, Hildick-Smith D, Uppal R, Kendall S, Bridgewater B. Eur J Cardiothorac Surg. 2016 Apr;49(4):1164-73. doi: 10.1093/ejcts/ezv270. Epub 2015 Aug 13.
17. Impact of renal function on survival after transcatheter aortic valve implantation (TAVI): an analysis of the UK TAVI registry. Ferro CJ, Chue CD, de Belder MA, Moat N, Wendler O, Trivedi U, Ludman P, Townend JN; UK TAVI Steering Group; National Institute for Cardiovascular Outcomes Research. Heart. 2015 Apr;101(7):546-52. doi: 10.1136/heartjnl-2014-307041. Epub 2015 Jan 12.
18. Comparative survival after transapical, direct aortic, and subclavian transcatheter aortic valve implantation (data from the UK TAVI registry). Fröhlich GM, Baxter PD, Malkin CJ, Scott DJ, Moat NE,Hildick-Smith D, Cunningham D, MacCarthy PA, Trivedi U, de Belder MA, Ludman PF, Blackman DJ; National Institute for Cardiovascular Outcomes Research. Am J Cardiol. 2015 Nov 15;116(10):1555-9. doi: 10.1016/j.amjcard.2015.08.035. Epub 2015 Sep 3.
19. Management of concomitant coronary artery disease in patients undergoing transcatheter aortic valve implantation: the United Kingdom TAVI Registry. Snow TM, Ludman P, Banya W, DeBelder M, MacCarthy PM, Davies SW, Di Mario C, Moat NE. Int J Cardiol. 2015 Nov 15;199:253-60. doi: 10.1016/j.ijcard.2015.06.166. Epub 2015 Jul 4.
20. Poor mobility predicts adverse outcome better than other frailty indices in patients undergoing transcatheter aortic valve implantation. Cockburn J, Singh MS, Rafi NH, Dooley M, Hutchinson N, Hill A, Trivedi U, de Belder A, Hildick-Smith D. Catheter Cardiovasc Interv. 2015 Dec 1;86(7):1271-7. doi: 10.1002/ccd.25991. Epub 2015 Jun 29.
21. Transcatheter aortic valve implantation in the United Kingdom: temporal trends, predictors of outcome, and 6-year follow-up: a report from the UK Transcatheter Aortic Valve Implantation (TAVI) Registry, 2007 to 2012. Ludman PF, Moat N, de Belder MA, Blackman DJ, Duncan A, Banya W, MacCarthy PA, Cunningham D, Wendler O, Marlee D,Hildick-Smith D, Young CP, Kovac J, Uren NG, Spyt T, Trivedi U, Howell J, Gray H; UK TAVI Steering Committee and the National Institute for Cardiovascular Outcomes Research. Circulation. 2015 Mar 31;131(13):1181-90. doi: 10.1161/CIRCULATIONAHA.114.013947. Epub 2015 Jan 30.
22. Long-term outcomes after transcatheter aortic valve replacement in high-risk patients with severe aortic stenosis: the U.K. Transcatheter Aortic Valve Implantation Registry. Duncan A, Ludman P, Banya W, Cunningham D, Marlee D, Davies S, Mullen M, Kovac J, Spyt T, Moat N. JACC Cardiovasc Interv. 2015 Apr 27;8(5):645-53. doi: 10.1016/j.jcin.2015.01.009.
23. Do outcomes from transcatheter aortic valve implantation vary according to access route and valve type? The UK TAVI Registry. Blackman DJ, Baxter PD, Gale CP, Moat NE, Maccarthy PA,Hildick-Smith D, Trivedi U, Cunningham D, DE Belder MA, Ludman PF; National Institute for Cardiovascular Outcomes Research (NICOR). J Interv Cardiol. 2014 Feb;27(1):86-95. doi: 10.1111/joic.12084. Epub 2013 Dec 30.
24. Device-dependent association between paravalvar aortic regurgitation and outcome after TAVI. Dworakowski R, Wendler O, Halliday B, Ludman P, DeBelder M, Ray S, Moat N, Kovac J, Spyt T, Trivedi U, Hildick-Smith D, Blackman D, Marlee D, Cunningham D, MacCarthy PA. Heart. 2014 Dec;100(24):1939-45. doi: 10.1136/heartjnl-2013-305390. Epub 2014 Jul 22.
25. Device-dependent association between paravalvar aortic regurgitation and outcome after TAVI. Dworakowski R, Wendler O, Halliday B, Ludman P, DeBelder M, Ray S, Moat N, Kovac J, Spyt T, Trivedi U, Hildick-Smith D, Blackman D, Marlee D, Cunningham D, MacCarthy PA. Heart. 2014 Jul 22. pii: heartjnl-2013-305390. doi: 10.1136/heartjnl-2013-305390.
26. Provision of cardiopulmonary bypass and surgical backup during TAVI: impact on surgical services. Spiro JR, Venugopal V, Ludman PF, Townend JN, Doshi SN; on behalf of the UK TAVI Steering Gropup. Br J Cardiol 2014;21:113–14 doi: 10.5837/bjc.2014.027
27. Influence of gender on clinical outcomes following transcatheter aortic valve implantation from the UK transcatheter aortic valve implantation registry and the National Institute for Cardiovascular Outcomes Research. Al-Lamee R, Broyd C, Parker J, Davies JE, Mayet J, Sutaria N, Ariff B, Unsworth B, Cousins J, Bicknell C, Anderson J, Malik IS, Chukwuemeka A, Blackman DJ, Moat N, Ludman PF, Francis DP, Mikhail GW. Am J Cardiol. 2014 Feb 1;113(3):522-8. doi: 10.1016/j.amjcard.2013.10.024. Epub 2013 Nov 9.
28. The 2011-12 pilot European Sentinel Registry of Transcatheter Aortic Valve Implantation: in-hospital results in 4,571 patients. Di Mario C, Eltchaninoff H, Moat N, Goicolea J; Ussia GP, MD; Kala P,Wenaweser P, Zembala M; Nickenig G, Barrero EA, Snow T; Iung B, Zamorano P; Schuler G; Corti R, Alfieri O; Prendergast B; Ludman P; Windecker S; Sabate M, Gilard M, Witkowski A, Danenberg H, Schroeder E, Romeo F, Macaya C, Derumeaux G, Maggioni A, Tavazzi L: on behalf of the Transcatheter Valve Treatment Sentinel Registry (TCVT) Investigators of the EURObservational Research Programme (EORP) of the European Society of Cardiology. Eurointervention 2013;8:1362
29. Stand-alone balloon aortic valvuloplasty: indications and outcomes from the UK in the transcatheter valve era. Khawaja MZ, Sohal M, Valli H, Dworakowski R, Pettit SJ, Roy D, Newton J, Schneider H, Manoharan G, Doshi S, Muir D, Roberts D, Nolan J, Gunning M, Densem C, Spence MS, Chowdhary S, Mahadevan VS, Brecker SJ, Maccarthy P, Mullen M, Stables RH, Prendergast BD, de Belder A, Thomas M, Redwood S, Hildick-Smith D. Catheter Cardiovasc Interv. 2013 Feb;81(2):366-73. doi: 10.1002/ccd.24534.
30. The UK transcatheter aortic valve implantation registry; one of the suite of registries hosted by the National Institute for Cardiovascular Outcomes Research (NICOR). Ludman PF; UK TAVI Steering Group and the National Institute for Cardiovascular Outcomes Research. Heart. 2012 Dec;98(24):1787-9. doi: 10.1136/heartjnl-2012-302534. Epub 2012 Aug 9. Review.
31. Long-term outcomes after transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis: the U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry. Moat NE, Ludman P, de Belder MA, Bridgewater B, Cunningham AD, Young CP, Thomas M, Kovac J, Spyt T, MacCarthy PA, Wendler O, Hildick-Smith D, Davies SW, Trivedi U, Blackman DJ, Levy RD, Brecker SJ, Baumbach A, Daniel T, Gray H, Mullen MJ. J Am Coll Cardiol. 2011 Nov 8;58(20):2130-8. doi: 10.1016/j.jacc.2011.08.050. Epub 2011 Oct 20.

BCIS R&D Group

Literature Review November 2019

Prepared by: Michael Mahmoudi, Aung Myat & Julian Gunn

 

STABLE CAD & ACS

Consistent benefits with complete revascularization in STEMI patients

Complete Revascularization with Multivessel PCI for Myocardial Infarction

NEJM 2019; 381:1411-21
Four intermediate-sized trials have shown that complete revascularization in patients presenting with STEMI and multivessel CAD is safe and reduces the risk of repeat revascularization. A general strategy of complete revascularization has not been shown to reduce the risk of hard endpoints such as death or MI. The COMPLETE trial randomized 4041 patients presenting with STEMI and multivessel CAD to either complete revascularization (n=2016) or culprit-lesion-only PCI (n=2025). Nonculprit lesions were considered angiographically significant if they were associated with at least 70% stenosis on visual estimation or with 50-69% stenosis accompanied by FFR<0.8. Patients randomized to complete revascularization were to have routine staged PCI of all suitable nonculprit lesions regardless of if there were clinical symptoms or there was evidence of ischaemia within 45 days of randomization. The first coprimary outcome was the composite of death from CV causes or new MI; the second coprimary outcome was the composite of death from CV causes, new MI, or ischaemia-driven revascularization. Safety outcomes included major bleeding and contrast-associated acute kidney injury. At a median follow-up of 3 years, the first coprimary was lower in the complete revascularization group (7.8% vs. 10.5%; HR, 0.74; 95% CI, 0.60-0.91; p=0.004). The second coprimary endpoint was also lower in the complete revascularization group (8.9% vs. 16.7%; HR, 0.51; 95% CI, 0.43-0.61; p<0.001). The rates of major bleeding, stroke, stent thrombosis, and acute kidney injury were similar in the two groups.

 

PCI and CABG excel at 5 years

Five-Year Outcomes after PCI or CABG for Left Main Coronary Disease

NEJM 2019; 381:1820-30
The role of PCI in patients with left main CAD is not clearly established. The EXCEL trial randomized 1905 patients with left main CAD of low or intermediate SYNTAX score (<32) to either PCI with the cobalt-chromium everolimus-eluting stents or CABG. The primary endpoint was the composite of death from any cause, stroke, or MI at 3 years. Major secondary endpoints included the primary endpoint at 30 days and the composite of death, stroke, MI, or ischemia-driven revascularization at 3 years. Long-term additional secondary outcomes included these measures and their components at 5 years, as well as therapy failure (definite stent thrombosis or symptomatic graft stenosis or occlusion), all revascularizations, and all cerebrovascular events (stroke or transient ischemic attack). At 5 years, the primary endpoint was similar in the PCI and CABG groups (22.0% vs. 19.2%; difference, 2.8 percentage points; 95% CI, −0.9-6.5; p=0.13). Death from any cause was greater in the PCI group (13.0% vs. 9.9%; difference, 3.1 percentage points; 95% CI, 0.2-6.1). The incidences of definite cardiovascular death (5.0% vs. 4.5%; difference, 0.5 percentage points; 95% CI, −1.4-2.5) and MI (10.6% vs. 9.1%; difference, 1.4 percentage points; 95% CI, −1.3-4.2) were similar. All cerebrovascular events were less frequent with PCI (3.3% vs. 5.2%; difference, −1.9 percentage points; 95% CI, −3.8-0), although the incidence of stroke was not significantly different between the two groups (2.9% vs. 3.7%; difference, −0.8 percentage points; 95% CI, −2.4-0.9). Ischemia-driven revascularization was greater in the PCI group (16.9% vs. 10.0%; difference, 6.9 percentage points; 95% CI, 3.7-10.0).

 

Further support for PCI in mutilvessel CAD

Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial

Lancet 2019;394:1325-34
The original SYNTAX trial was an international multicentre randomised controlled trial performed in 85 hospitals across 18 North American and European countries. Patients with de novo 3-vessel or left main coronary artery disease were randomised in a 1:1 fashion to revascularisation either by PCI with a first-generation drug-eluting stent versus coronary artery bypass graft surgery. The original trial spawned the concept of a Heart Team reaching a consensus on anatomic complexity that would allow for presumed equipoise in terms of suitability for PCI or CABG. Published in 2009, the trial demonstrated 1 year MACCE to be significantly higher in the PCI group (17.8% vs. 12.4% for CABG; p=0.002), driven primarily by the need for repeat revascularisation after coronary stenting. Rates of death and MI were similar, but stroke occurred significantly more often after CABG. At 5-year follow-up, published in the Lancet in 2013, CABG remained superior for complex lesions (high or intermediate SYNTAX scores, ≥33 and 23-32 respectively), driven by significantly higher rates of repeat revascularisation and MI in the PCI arm. Interestingly, in less complex disease (low SYNTAX scores 0-22) or left main coronary disease (low or intermediate SYNTAX scores), PCI was found to be an acceptable mode of revascularisation. The latter finding was the basis upon which the EXCEL trial pitted a second-generation DES versus CABG for left main coronary artery disease with low or intermediate SYNTAX scores. At 10-year follow-up of the SYNTAX trial, life status was complete for the vast majority of the original cohort (93% PCI vs. 95% CABG). There was no significant difference in all-cause mortality between either revascularisation modality (HR 1.17, 85% CI 0.97-1.41; p=0.092). All-cause mortality rates favoured CABG after stratification by 3-vessel disease (HR1.41, 95% CI 1.10-1.80) but remained equivalent for left main coronary artery disease (HR 0.90, 95% CI 0.68-1.20; p value for interaction=0.019). The latter lending further credence to the results emanating from the 3- and 5-year follow-up data from EXCEL. There was also no treatment-by-subgroup interaction relative to diabetes status. How transferable these results are in an age of newer-generation DES where the haemodynamic significance of a lesion is routinely assessed by invasive physiology remains a topic of contention.

 

DEBs are finding indications beyond in-stent restenosis

Drug-coated balloon for treatment of de-novo coronary artery lesions in patients with high bleeding risk (DEBUT): a single-blind, randomised, non-inferiority trial

Lancet 2019;394:230-39
There is limited data on the clinical effectiveness of drug-coated balloons (DCB) for the treatment of obstructive coronary lesions in standard-sized vessels in those with high bleeding risk. Previous trials have focussed on comparing drug-coated balloons against first- and second-generation DES in small coronary artery disease. The Drug-Eluting Balloon in stable and Unstable angina (DEBUT) trial was a non-inferiority trial of 208 patients randomised to DCB (n=102) or bare-metal stent (BMS: n=106). An individual was deemed at high bleeding risk if they had just one recognised risk factor from a list of 11 pre-specified variables. No reference was made to established high bleeding risk scores such as HAS-BLED, ATRIA or CRUSADE. Moreover the predominant factors determining a high bleeding risk in the trial were age ≥80, baseline anaemia or thrombocytopenia and chronic oral anticoagulation use. In its favour the trial protocol did mandate an objective measure of ischaemia in the context of stable CAD, either by non-invasive imaging or pressure wire study before inclusion in the trial. Randomisation took place after the initial balloon predilation of the target lesion, subsequent dissection or >30% recoil of the target vessel precluded trial entry. Dual antiplatelet therapy was continued for 1 month after the procedure, in the context of both stable CAD and ACS. Aspirin was continued for 6 months in those presenting on oral anticoagulation. At 9-months the primary composite endpoint of MACE (CV mortality, non-fatal MI, or ischaemia-driven TLR) had occurred in just one patient (1%) in the DCB group versus 15 patients (14%) in the BMS group (p<0.0001 for non-inferiority and p=0.00034 for superiority). There were no cases of acute vessel closure after DCB treatment and no patients required TLR in the DCB arm versus 6 patients (6%) after BMS implantation. There was no significant difference in bleeding events. Key to the success of the DCB strategy was optimal lesion preparation, which was adhered to stringently in the trial. The difference between DCB versus BMS remained significant up to 36-month follow-up, which was a pre-specified secondary endpoint.

 

MgBRS provides further conflicting results for bioresorbable enthusiasts

Magnesium-Based Resorbable Scaffold versus Permanent Metallic Sirolimus Eluting Stent in Patients with ST-Segment Elevation Myocardial Infarction: The MAGSTEMI Randomized Clinical Trial

Circ 2019 Online
The use of first generation poly-L lactic acid-based bioresorbable scaffolds has been hampered by safety concerns. Magnesium-based bioresorbable scaffold (MgBRS) has short resorption period as well as being thromboresistant. Given the lack of data regarding the performance of MgBRS, the MAGSTEMI trial was designed to compare the in-stent/scaffold vasomotion between MgBRS and permanent metallic sirolimus-eluting stent (SES) at 12-month follow-up in 150 STEMI patients undergoing PPCI. The primary endpoint was the rate of increase (≥3%) after nitroglycerin in mean lumen diameter of the in-stent/scaffold segment with superiority of MgBRS over SES. Main secondary endpoints included angiographic parameters of restenosis, the device-oriented composite endpoint, their individual components, and device thrombosis rate. At 1-year follow-up, the primary endpoint was higher in the MgBRS group (56.5% vs. 33.8%; p=0.01). Late lumen loss was lower in the SES group (in-segment: 0.39±0.49mm vs. 0.02±0.27); p<0.001; in-device: 0.61±0.55 vs. 0.06±0.21; p<0.001). The device-oriented composite endpoint was higher in the MgBRS due to an increase in ischaemia driven TLR (16.2% vs. 5.2%; p=0.03). Definite ST rates were similar (1.4% vs. 2.6%; p=1.0). Endothelial function assessment at device segment was more pronounced in the MgBRS group (-8.3±3.5% vs. -2.4±1.3%; p=0.003).

 

ANTIPLATELET THERAPY

 

Ticagrelor monotherapy for high risk PCI?

Ticagrelor with or without Aspirin in High-Risk Patients after PCI

NEJM 2019 Online
Despite the use of DAPT in patients presenting with ACS or who have undergone PCI, the risk of ischaemic complications remains significant. The TWILIGHT trial was designed to test the hypothesis that in patients undergoing PCI who are at high risk of ischemic or haemorrhagic complications and who have completed a 3-month course of DAPT with ticagrelor plus aspirin, continued treatment with ticagrelor monotherapy would be superior to ticagrelor plus aspirin. The primary endpoint was BARC type 2, 3, 04 5 bleeding. The key secondary endpoint was death from any cause, nonfatal MI, or nonfatal stroke. Clinical criteria for high risk were age ≥ 65 years, female sex, troponin positive ACS, established vascular disease, diabetes mellitus, and CKD. Angiographic criteria included multivessel CAD, stent length >30mm, a thrombotic target lesion, bifurcation lesion treated with two stents, an obstructive left main or proximal LAD lesion, and a calcified target lesion treated atherectomy. The study enrolled 9006 patients and 7119 underwent randomization after 3 months of DAPT. At 1 year the primary endpoint was lower in the ticagrelor monotherapy group (4% vs. 7.1%; HR, 0.56; 95% CI, 0.45-0.68; p<0.001). The incidence of death from any cause, nonfatal MI or stroke was 3.9% in both groups (difference, -0.06 percentage points; 95% CI, -0.97-0.84, HR, 0.99; p<0.001 for noninferiority).

 

Should prasugrel replace ticagrelor in ACS patients?

Ticagrelor or Prasugrel in Patients with Acute Coronary Syndromes

NEJM 2019; 381:1524-34
The safety and efficacy of prasugrel versus ticagrelor in patients with ACS has not been adequately compared in a head to head fashion. The ISAR-REACT-5 trial randomized 4018 patients, who presented with ACS and for whom invasive evaluation was planned, to receive either ticagrelor or prasugrel. Patients who were assigned to ticagrelor received the loading dose as soon as possible after randomization and maintained at 90mg BD. Prasugrel was started at a loading dose of 60mg and maintained at 10mg OD. A reduced maintenance dose of 5mg OD was recommended in patients who were ≥ 75 years old, and in those who had a body weight < 60 Kg. The primary endpoint (a composite of death, MI, or stroke at 1 year) was lower in the prasugrel group (6.9% vs. 9.3%; HR, 1.36; 95% CI, 1.09-1/70; p=0.006), with a number needed to treat of 42. This result was driven by a significant reduction of 1.8 percentage points in the incidence of recurrent MI and no significant between-group difference in the incidence of major bleeding (4.8% vs. 5.4%; p=0.46).

 

Ticagrelor not indicated in type II DM and stable CAD

Ticagrelor in Patients with Stable Coronary Disease and Diabetes

NEJM 2019; 381:1309-20
The PARTHENON clinical development program for ticagrelor has included four randomized, controlled, double blind trials across the spectrum of CV disease (PLATO, SOCRATES, EUCLID, PEGASUS-TIMI 54). The THEMIS study, the final PARTHENON trial, examined the safety and efficacy of ticagrelor in 19220 patients who were 50 years of age or older and who had type 2 diabetes mellitus and stable CAD to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with a previous history of MI or stroke were excluded. The presence of stable CAD was determined by one of the following: history of PCI or CABG or documentation of angiographic stenosis of at least 50% in at least one coronary artery. After a median follow-up of 39.9 months, the primary composite efficacy outcome of CV death, MI or stroke favoured DAPT with ticagrelor (7.7% vs. 8.5%; HR, 0.90; 95% CI 0.81-0.99; p=0.04), but the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; HR, 2.32; 95% CI, 1.82-2.94; p<0.001), and there was an excess of intracranial haemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18-2.48; p=0.005). There was no reduction in the composite outcome of irreversible harm, which was defined as death from any cause, MI, stroke, fatal bleeding, or intracranial haemorrhage (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86-1.02).

 

Another positive milestone for personalized medicine

A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI

NEJM 2019; 381:1621-31
Given the genetic variants in CYP2C19 the Popular Genetics trial was designed to determine whether a CYP2C19 genotype-guided strategy for selection of oral P2Y12 inhibitors could reduce bleeding risk without increasing thrombotic risk in patients with STEMI undergoing PPCI. 2488 were randomized to receive either a P2Y12 inhibitor on the basis of early CYP2C19 genetic testing (genotype-guided group) or standard treatment with either ticagrelor or prasugrel (standard treatment group) for 12 months. In the genotype-guided group, carriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles received ticagrelor or prasugrel, and noncarriers received clopidogrel. There were two primary outcomes. The first was the combined outcome of net adverse clinical events, which included death from any cause, MI, definite stent thrombosis, stroke, PLATO major bleeding at 12 months. The second was PLATO major or minor bleeding at 12 months. The primary combined outcome was lower in the genotype-guided group (5.1% vs. 5.9%; absolute difference, −0.7 percentage points; 95% CI, −2.0-0.7; p<0.001 for noninferiority). The primary bleeding outcome was also lower in the genotype-guided group (9.8% vs. 12.5%; HR, 0.78; 95% CI, 0.61-0.98; p=0.04).

 

CORONARY PHYSIOLOGY

 

Utilization of coronary physiology to guide CABG

Graft patency after FFR-guided versus angiography-guided coronary artery bypass grafting. The GRAFFITI trial

EuroIntervention 2019 Online
In contrast to the wealth of data supporting the use of physiological indices to guide PCI, there are few to guide CABG. The GRAFFITI trial was a multi-centre, multi-national study of 172 patients undergoing coronary angiography, with either a chronic or acute presentation, having a significant lesion of the LMS or LAD and at least one more major vessel, making them potentially suitable for CABG. These patients then all underwent pressure wire examination. They were then randomised to FFR vs. visually guided CABG. The primary endpoint was graft patency at 12 months. Patients had a median three lesions. Compared to the angiography-guided group, the FFR-guided group received fewer anastomoses (3.0 vs. 2.0; p=0.004). One-year angiographic follow-up showed no difference in overall graft patency, death, MI, TVR or stroke.

 

Size does matter in CTO PCI

Relationship between Extent of Ischaemic Burden and Changes in Absolute Myocardial Perfusion after Chronic Total Occlusion Percutaneous Coronary Intervention

EuroIntervention 2019 Online
In this single centre study, 193 consecutive patients who had undergone successful CTO PCI underwent [15O]H2O PET at three months. They had also had a similar scan before PCI. The change in perfusion defect size, quantitative hyperaemic myocardial blood flow (MBF) and coronary flow reserve (CFR) in the CTO area were compared. Patients were subdivided according to the size of the perfusion defect into limited (0-1 segment, N=15), moderate (2-3 segments, N=61) and large (≥4 segments, N=117) defects. The median reductions in defect size were 1 [0-1], 2 [1-3], and 4 [2-5] segments in patients in these groups, respectively (all p<0.01). Hyperaemic MBF and CFR improved significantly regardless of baseline defect size. This study appears to support the concept that the larger the area of myocardium supplied by a CTO, the larger the potential benefit with successful revascularization.

 

CRUSH, CALCIFICATION, & BEYOND

 

The rise of coronary lithotripsy as an alternative to rotablation

Safety and Effectiveness of Coronary Intravascular Lithotripsy for Treatment of Severely Calcified Coronary Stenoses. The Disrupt II Study

Circ Cardiovasc Interv 2019; 12:e008434
The feasibility of coronary intravascular lithotripsy (CIVL) to modify coronary calcification has been confirmed in the Disrupt CAD I study. The Disrupt II study was designed to confirm the safety and efficacy of CIVL in 120 patients in whom 94.2% had severe calcification. Delivery and use of the CIVL was achieved in all patients. Post CIVL angiographic luminal gain was 0.83±0.47mm, and residual stenosis was 32.7±10.4%, which further decreased to 7.8±7.1% post DES implantation. The primary endpoint of in-hospital MACE defined as cardiac death, MI, or TVL was 5.8%. There was no procedural abrupt vessel closure, slow or no reflow, or perforations. In 47 patients who underwent OCT post CIVL, calcium fracture was identified in 78.7% of lesions with 3.4±2.6 fractures per lesion.

 

A double crush for distal LMS disease

3-Year Outcomes of the DKCRUSH-V Trial Comparing DK Crush With Provisional Stenting for Left Main Bifurcation Lesions

JACC Intv 2019; 12:1927-37
The Double Kissing Crush versus Provisional Stenting for Left Main Distal Bifurcation Lesions (DKCRUSH-V) randomized trial demonstrated lower TLF and ST at 1-year follow-up in the DK crush group. The aim of the current study was to evaluate the 3-year clinical outcomes of the DKCRUSH-V study. At 3 years, TLF remained lower in the DK group (8.3% vs. 16.9%; p=0.005), driven by increased target vessel MI (1.7% vs. 5.8%; p=0.017) and target lesion revascularization (5.0% vs. 10.3%; p=0.029). Definite or probable ST was also lower in the DK group (0.4% vs. 4.1%; p=0.006).

 

Grave consequences of stent thrombosis

Incidence and predictors of outcomes after a first definite coronary stent thrombosis

EuroIntervention 2019 Online
The authors performed a retrospective analysis of the clinical outcomes of all 695 cases of definite stent thrombosis occurring in two major European centres, Rotterdam and Bern, over the period 1996-2017. They also presented their intravascular imaging findings. The mean age was 63 years and 76% were male. The timing of thrombosis was front-loaded after the index event (IQR 3-551, median 22 days) but with a very long ‘tail’ so that numbers were evenly divided between early and late or very late. Intravascular imaging was performed in 197 cases. In patients with early stent thrombosis, a quarter was associated with malapposition, a quarter with under-expansion and a quarter with edge dissection. In the late cases, 2/3 was associated with neotherosclerosis and 1/3 with malapposition. At 5 years after the thrombosis event, MACE occurred in 44%, of which cardiac death accounted for 20%; 18% experienced a further MI, TVR was required in 25% and repeat definite stent thrombosis occurred in 12%. Predictors of adverse outcomes after stent thrombosis were the presence of cardiogenic shock, location in the LAD, prior CVA/TIA or peripheral vascular disease, multivessel disease and final TIMI flow <3. No specific treatment, such as thrombectomy or GP IIb/IIIa inhibitor, seemed to influence MACE although new generation P2Y12 inhibitors reduced the risk of MI.

 

The perivascular fat attenuation index (FAI) derived via CTCA is a promising tool for monitoring coronary inflammation

Association of Biologic Therapy with Coronary Inflammation in Patients with Psoriasis as Assessed by Perivascular Fat Attenuation Index

JAMA Cardiol 2019; 4:885-91
The link between systemic inflammatory disorders and CAD are well established. In psoriasis biological therapy has been found to be favourably associated with luminal coronary plaques. Whether these associations are related to direct anti-inflammatory effects are unknown. In this study of 134 patients who predominantly had low CV risk and moderate to severe skin disease, investigators examined changes in the perivascular fat attenuation index (FAI), a novel imaging biomarker to assess coronary inflammation by mapping spatial changes of perivascular fat composition via CTCA, at baseline and at 1 year follow-up. Of these patients, 82 received biologic psoriasis therapy (anti-TNF, anti-IL12/23, or anti-IL 17) for 1 year and 52 did not receive any biologic therapy and were given topical or light therapy (control group). Biologic therapy was associated with a significant decrease in FAI at 1 year (median FAI −71.22 HU at baseline vs. −76.09 HU at 1 year; p < 0.001) concurrent with skin disease improvement (median PASI, 7.7 at baseline vs. 3.2 at 1 year; p < 0.001), whereas no change in FAI was noted in those not receiving biologic therapy (median FAI, −71.98 at baseline vs. −72.66 at 1 year; p =0.39). The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents.

 

The return of the polypill

Effectiveness of polypill for primary and secondary prevention of cardiovascular disease (PolyIran): a pragmatic, cluster-randomised trial

Lancet 2019;394:672-83
The premise underpinning the use of a polypill, containing a fixed-dose combination of an anti-hypertensive agent(s), cholesterol-lowering drug, and aspirin, for the primary and secondary prevention of cardiovascular disease appears intuitively to be a good idea. It should maximise patient compliance and has the potential to save money. This is potentially of greater value to those living in low- and middle-income countries, where healthcare provision can be disjointed at best and haphazard at worst. Despite these obvious benefits, the widespread use of a polypill has not gained significant traction globally, in the most part due to previous trials being hampered by small to moderate sample sizes and abbreviated follow-up durations thereby limiting their power to determine the long-term effects of polypills on hard endpoints. The PolyIran study was a cluster-randomised trial nested within the much larger Golestan Cohort Study in Iran. Between February 2011 and April 2013, 6838 individuals were randomised to a minimal care group (n=3417) versus a once-daily polypill (n=3421) cohort. Almost half of each group consisted of women. The two largest polypill trials to date had enrolled just over 2000 individuals each. Minimal care comprised regular education on a healthy lifestyle including diet, exercise, weight control and abstinence from smoking and opium consumption. Polypill one consisted of hydrochlorothiazide 12.5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg. Those who developed cough were changed to Polypill two in which valsartan 40 mg replaced enalapril. Follow-up extended to 60 months after the last patient was enrolled. The two largest polypill trials to date had previously followed-up to 12 weeks and 15 months. Nearly 11% of the entire cohort had pre-existing cardiovascular disease, and of these 79.8% were using cardiovascular drugs at baseline. By the end of the study 8.8% in the minimal care group had had a major CV event (a composite of ACS hospitalisation, fatal MI, sudden death, heart failure, PCI, and non-fatal and fatal stroke) versus 5.9% in the polypill group (HR 0.66, 95% CI 0.55-0.80). When stratified according to high adherence to the polypill the difference to minimal care was even more pronounced (HR 0.43, 95% CI 0.33-0.55). Adverse events were similar between the two groups. Given the relatively large sample size and extended follow-up period, this trial offers a significant contribution to the evidence base for polypills especially in the primary prevention of cardiovascular disease and will serve as a benchmark for future studies in this therapeutic area. Whether a fixed-dose combination is of relevance for secondary prevention of cardiovascular disease, particularly in the developed world where there is now an onus on optimising, and thus up-titrating drug doses, remains to be seen. The next logical step therefore would be to determine the non-inferiority of a fixed-dose combination polypill against standard of care in a secondary prevention setting where the comparator group would be encouraged to up-titrate individual components of the pharmacotherapeutic regimen.

1. INTRODUCTION

Service Specification for Transcatheter Aortic Valve Implantation (TAVI)

Recommendations of the British Cardiovascular Intervention Society (BCIS) – updated July 2019

1. Introduction

Severe aortic stenosis (sAS) is the most common primary valve disease leading to surgery or catheter intervention in Europe and North America, with a growing prevalence due to the ageing population.1 It is a degenerative condition where the outflow of blood from the heart is restricted by progressive narrowing of the aortic valve. This leads to symptoms of breathlessness, exertional chest pain or blackouts. Untreated, the condition causes left ventricular failure and death, with up to 40% of patients dying within 1 year of symptom onset. No medical therapy can improve outcome for this condition and therefore valve intervention is the only treatment option which alters prognosis. The standard of care for this condition has historically been surgical Aortic Valve Replacement (sAVR), but around 1/3 of patients are ineligible for sAVR due to a combination of age and comorbidities.

TAVI is a transformational technology which is a much less invasive approach than sAVR and involves implantation of a new valve without the need for complex surgery or the use of a heart-lung bypass machine. This is most commonly done via the femoral arteries (transfemoral or TF approach) but may also be accomplished via the subclavian arteries or via minimally invasive access using the cardiac apex between the ribs, directly into the aorta through a small incision. Less common approaches via the carotid arteries, axillary artery and the femoral veins / abdominal aorta have also been described. Therefore, for the majority of patients undergoing TAVI, the procedure is performed via the femoral artery, under local anaesthesia/ conscious sedation in a catheter laboratory. This results in quicker patient recovery, shorter hospital stay and reduced use of expensive and limited resources such as cardiac operating theatres and intensive care unit beds, as well as post-operative nursing care.

A number of different valve designs are available, including balloon-expandable and self-expandable devices. Each has different performance characteristics, which may be tailored to specific anatomical or patient-specific features.

TAVI has been proven to be superior to medical therapy for inoperable patients and superior to sAVR in patients who are high risk for sAVR (Society of Thoracic Surgeons (STS) or Euroscore II >8%).2-4 Trials have also shown that patients with intermediate surgical risk (STS or Euroscore II >4%) who are eligible for a transfemoral approach have superior outcomes with TAVI.5-7 Moreover, randomised trials have shown TAVI

to be superior to sAVR in patients classified as ‘low risk’ (STS<4) with outcome data so far published to 12 months 8,9

2. ENTRY TO CARE PATHWAY

Indications for aortic intervention by means of TAVI or sAVR include severe Aortic Stenosis (sAS) and any of the following:

1. Symptoms related to sAS
2. Left ventricular dysfunction related to sAS
3. Evidence of very severe AS, or rapid increase in echo severity
4. Abnormal exercise test or elevated cardiac biomarkers (BNP)
5. Severe bioprosthetic valve failure

After appropriate investigations including (but not limited to) transthoracic echocardiography and cardiac / peripheral CT scanning, patients should be discussed by an appropriately constituted Multidisciplinary Heart Team (MDT – the Heart Team) as per BCS/ SCTS/ BCIS guidelines – see below10. After taking into account age, frailty and comorbidities, MDT outcome will be:

1. sAVR
2. TAVI
3. Conservative/medical management

Recommendations 1 or 2 will be made by taking into account the cardiac and extracardiac characteristics of the patient, the individual risk of surgery, which is assessed by the judgement of the Heart Team, in addition to risk scoring and the technical and anatomical feasibility of TAVI.

Validated calculators of conventional surgical risk (e.g. Euroscore 2 or STS score) have several limitations in selecting patients to undergo TAVI and are now generally not used clinically. Specifically, they do not assess frailty, degree of disability, echocardiographic/anatomical features or important comorbidities. Therefore, patient selection for TAVI requires consideration of the whole patient as well as several prognostic variables.

Technical aspects which may favour TAVI or sAVR should be assessed by detailed review of all investigations. Technical factors for potential TAVI should include suitability for transfemoral access (which is associated with the lowest risk) and risk factors for adverse events such as coronary occlusion, annular trauma and paravalvar leak. Additional adverse features for sAVR which are not represented in surgical calculators should be noted. These include presence of severe aortic calcification, liver disease, chest wall deformity and previous thoracic radiotherapy.

Medical management may be recommended when comorbidities and frailty are so severe that no improvement in quality of life or prognosis is expected from intervention ie. Intervention is thought to be futile. Therefore, the MDT should refer to reports from other specialists with regard to prognosis and severity of other conditions. This may include memory clinic assessments for patients with cognitive impairment as significant dementia is likely to negate any benefit from intervention.

 

The table shown in Figure 1 (below) is taken from the latest European guidelines but is already outdated. However, it illustrates a list of patient features which should be considered by the Heart Team in deciding whether sAVR or TAVI is appropriate in individual cases.

The MDT should refer to up to date guidelines on valve intervention (e.g. NICE, ESC / EACTS 2017 Guidelines for the management of valvular heart disease1) in order to inform decision-making. This is especially important, as this is a rapidly evolving literature and there are several trials in different patient groups underway which will further advance the evidence base for therapy.

Given the time dependency of treatment in the outcome of patients with sAS, it is vital that after MDT discussion, recommended therapy should be offered promptly – see section 8a below. AS has an extremely poor prognosis and patients will die on the waiting list for treatment. BCIS recommends that regular review of mortality of patients on waiting lists is performed by all TAVI centres. The absolute maximum waiting time from point of referral to the definitive valve procedure should be 18 weeks.

FIG 1 CLINICAL CHARACTERISTICS TAVI / SAVR

3. MDT STRUCTURE

Each MDT should involve a minimum of one TAVI interventionist, one cardiac surgeon, one imaging/general cardiologist and should have appropriate administrative support.10 Direct MDT input from other specialties (Elderly Care medicine, anaesthetics) will be required for some patients and local pathways should be developed for this input to be available quickly. MDT meetings should occur at least weekly sufficiently frequently to ensure that unnecessary delays do not occur. Arrangements should also be put in place for ad hoc MDT discussion of urgent patients who may present between formal MDT meetings. Adequate documentation with dissemination of decisions should be prioritised.

Several studies have demonstrated the importance of the TAVI Clinical Nurse Specialist/Co-ordinator which BCIS considers a mandatory component of the Heart Team (MDT) and every TAVI centre.

4. FOLLOW-UP POST INTERVENTION

Following TAVI and at the point of discharge, the implanting team should document the recommended medical therapy and set out arrangements for further follow up. First follow up visit should be within 6-8 weeks in order to assess any possible adverse effects of treatment. This will usually be with the implanting centre. Subsequent follow up arrangements should be according to guidelines for bioprosthetic valve intervention – usually annually with echocardiographic assessment.1 Patients can be followed up by their local Cardiology service after the first review at the TAVI centre.

 

5. INTERDEPENDENCE WITH OTHER SERVICES

BCIS recommends that a TAVI centre should fulfil the following criteria: Essential on-site services:

a. MDT. Constituted as above (see section 3).

b. Imaging. A sophisticated echo and CT service is essential for proceduralplanning, vascular access assessment and valve sizing. At least one Consultant should be assigned to the Heart Team to lead the imaging aspect of the service.

c. ITU. An on-site ITU is mandatory in order to manage multi-system dependence or complications of the procedure. In this regard, on-site access to renal replacement therapy is required.

d. Cardiac surgery.Emergency cardiac surgery for complications is uncommon during transfemoral TAVI, with the latest registry data of 27,760 patients in Europe suggesting an incidence of <1%11. Although infrequent, the commonest complications requiring emergency surgical bailout include left ventricular perforation by guide wire and annular rupture, which are immediately life threatening and can only be successfully treated with immediate surgery. Therefore, on site cardiac surgery is an absolute requirement to support a TAVI service and is recommended by ESC / EACTS and North American guidelines.12 TAVI via thoracic approaches (e.g. transapical, direct aortic) are led by cardiac surgeons.

e. Vascular/Interventional Radiology/Vascular surgery. Vascular complications are the commonest adverse events during transfemoral TAVI, so robust arrangements are needed to deal with these emergently. Vascular bailout may be performed by open surgery or percutaneous techniques. Vascular interventional radiology/vascular surgery expertise should be immediately available allowing access to equipment and techniques for percutaneous management of complications (occlusion balloons, guidewires and peripheral stents) or open vascular surgery as needed. TAVI centres should have a local Standard Operating Policy SOP for these clinical events to ensure that emergencies are managed effectively and systems are reviewed and updated frequently.

f. TAVI clinical nurse specialist/admin support. BCIS considers a co- ordinating TAVI Clinical Nurse Specialist an essential component of the TAVI team. Administrative support should also be provided for an effective MDM (see section 3 above).

6. EXPECTED SIGNIFICANT FUTURE DEMOGRAPHIC CHANGES

In keeping with the degenerative nature of the condition, the ageing population will require a growth in TAVI implantation rates. In addition, newer data suggests efficacy of TAVI (vs sAVR) across the spectrum of risk in patients with AS, including studies in patients at low surgical risk who currently undergo sAVR 8,9.

7. CURRENT EVIDENCE BASE FOR TAVI IN TREATING SAS

Several large randomised controlled trials (RCT) have been published, which may be briefly summarised as follows:

• Inoperable / extreme risk patients: TAVI superior to medical therapy. (PARTNER 1B trial)2
• High risk patients (mortality risk >8%): TF TAVI non-inferior or superior to sAVR (high risk Corevalve trial, PARTNER A trial)3-4
• Intermediate risk patients (mortality risk >4%; <8%): TF TAVI non-inferior or superior to sAVR (NOTION trial, PARTNER 2 trial, SURTAVI trial)5-7
• Low risk: TF TAVI superior to sAVR in patients at low risk (STS<4; PARTNER 3 – follow-up to 12 months to date 8) or equivalent in this patient population (Evolut low risk trial 9)These data have been reviewed extensively in the production of the updated ESC/EACTS 2017 guidelines 1 – but unfortunately, since the guideline publication, several more trials have been published, rendering them already out-of-date.

 

8. BCIS TAVI PATHWAY RECOMMENDATIONS

Goal of therapy: to offer eligible patients with sAS timely intervention to prevent premature death, improve symptoms and reduce hospitalisation, using a transformational, minimally-invasive treatment allowing rapid return to improved quality of life.

BCIS proposes the following guidelines:

a. TAVI pathway–maximum 18 weeks

• Referral to clinic <6wks
• Clinic to investigations/MDT discussion <6wks
• Decision MDT to TAVI <6wks

Regular local audit of service performance should be performed, including quality improvement projects/waiting list surveillance

b. TAVI volume per centre/operator – there is now published evidence to support improved outcomes with TAVI centre/operator volume 13

• New centres should aim for 50 cases per year/2 operators
• The aim should be for at least 100 cases/year i.e. 50 cases/operator in established centre to ensure volume experience and skill in more than one device
• The TAVI procedure should be performed by 2 appropriately trained TAVI operators

c. GA vs non-GA: Centres should aim for >90% cases non-GA

d. Length of Stay: 1-5 days. Level 3 beds should be used only in exceptional cases

e. Submission of the full UK TAVI dataset for all TAVI procedures to NICOR at least every quarter, with data for a quarter to be submitted by the end of the following quarter. 30-day mortality, stroke rate and vascular complications (as per VARC criteria) will be monitored (observed vs predicted) using the NICOR TAVI mortality model/funnel plots.

Details of all TAVI procedures and their outcomes are submitted to NICOR. Criteria for defining outlier performance is currently being agreed, but it is expected that the BCS Outlier policy will be used to implement Society advice. At present 30 day mortality and major complications including rate of vascular complication or stroke are used to measure safety. However other outcomes such as change in symptoms and quality of life may be used in the future.

Currently all departments receive performance outcomes adjusted for risk with funnel plots.

APPLICABLE OBLIGATORY NATIONAL / EUROPEAN STANDARDS

Applicable Obligatory National Standards

NICE IPG586: Transcatheter aortic valve implantation for aortic stenosis. July 2017

Other Applicable Standards to be met by Commissioned Providers

Adherence to ESC / EACTS 2017 Guidelines for the management of valvular heart disease or subsequent updates.

REFERENCES

1. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Baumgartner H et al. European Heart Journal, vol 38, Issue 36, 21 September 2018, Pages 2739-2791.
2. Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Investigators. Transcatheter aortic- valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010 Oct 21;363(17):1597-607.
3. SmithCR,LeonMB,MackMJ,MillerDC,MosesJW,SvenssonLG,TuzcuEM, Webb JG, Fontana GP, Makkar RR, Williams M, Dewey T, Kapadia S, Babaliaros V, Thourani VH, Corso P, Pichard AD, Bavaria JE, Herrmann HC, Akin JJ, Anderson WN, Wang D, Pocock SJ; PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011 Jun 9;364(23):2187-98.
4. Adams DH, Popma JJ, Reardon MJ, Yakubov SJ, Coselli JS, Deeb GM, Gleason TG, Buchbinder M, Hermiller J Jr, Kleiman NS, Chetcuti S, Heiser J, Merhi W, Zorn G, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Conte J, Maini B, Mumtaz M, Chenoweth S, Oh JK; U.S. CoreValve Clinical Investigators. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014 May 8;370(19):1790-8.
5. Thyregod HGH, Steinbrüchel DA, Ihlemann N, Nissen H, Kjeldsen BJ, Chang PPY, Franzen OW, Engstrøm T, Clemmensen P, Hansen PB, Andersen LW, Olsen PS, Søndergaard L. Transcatheter Versus Surgical Aortic Valve Replacement in Patients with Severe Aortic Valve Stenosis. 1- Year Results from the All-Comers NOTION Randomized Clinical Trial. J Am Coll Cardiol 2015; 65: 2184–94.
6. LeonMB,SmithCR,MackMJ,MakkarRR,SvenssonLG,KodaliSK,Thourani VH, Tuzcu EM, Miller DC, Herrmann HC, Doshi D, Cohen DJ, Pichard AD, Kapadia S, Dewey T, Babaliaros V, Szeto WY, Williams MR, Kereiakes D, Zajarias A, Greason KL, Whisenant BK, Hodson RW, Moses JW, Trento A, Brown DL, Fearon WF, Pibarot P, Hahn RT, Jaber WA, Anderson WN, Alu MC, Webb JG; PARTNER 2 Investigators. Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med. 2016 Apr 28;374(17):1609-20.
7. Reardon MJ, Van Mieghem NM, Popma JJ, Kleiman NS, Søndergaard L, Mumtaz M, Adams DH, Deeb GM, Maini B, Gada H, Chetcuti S, Gleason T, Heiser J, Lange R, Merhi W, Oh JK, Olsen PS, Piazza N, Williams M, Windecker S, Yakubov SJ, Grube E, Makkar R, Lee JS, Conte J, Vang E, Nguyen H, Chang Y, Mugglin AS, Serruys PW, Kappetein AP; SURTAVI Investigators. Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med. 2017 Apr 6;376(14):1321-1331.

8. MackMJ,LeonMB,ThouraniVH,MakkarR,KodaliSK,RussoM,KapadiaSR, Malaisrie SC, Cohen DJ, Pibarot P, Leipsic J, Hahn RT, Blanke P, Williams MR, McCabe JM, Brown DL, Babaliaros V, Goldman S, Szeto WY, Genereux P, Pershad A, Pocock SJ, Alu MC, Webb JG, Smith CR; PARTNER 3 Investigators. Transcatheter Aortic-Valve Replacement with a Balloon- Expandable Valve in Low-Risk Patients. N Engl J Med. 2019 May 2;380(18):1695-1705.
9. Popma JJ, Deeb GM, Yakubov SJ, Mumtaz M, Gada H, O’Hair D, Bajwa T, Heiser JC, Merhi W, Kleiman NS, Askew J, Sorajja P, Rovin J, Chetcuti SJ, Adams DH, Teirstein PS, Zorn GL 3rd, Forrest JK, Tchétché D, Resar J, Walton A, Piazza N, Ramlawi B, Robinson N, Petrossian G, Gleason TG, Oh JK, Boulware MJ, Qiao H, Mugglin AS, Reardon MJ; Evolut Low Risk Trial Investigators. Transcatheter Aortic-Valve Replacement with a Self-Expanding Valve in Low-Risk Patients. N Engl J Med. 2019 May 2;380(18):1706-171.
10. Joint Statement on clinical selection for Trans-catheter Aortic Valve Implantation (TAVI) 1/8/2017 On behalf of BCS, SCTS and BCIS. https://www.bcis.org.uk/wp-content/uploads/2017/08/TAVI-commissioning- statement-final.pdf
11. Eggebrecht H, Vaquerizo B, Moris C, Bossone E, Lämmer J, Czerny M, Zierer A, Schröfel H, Kim WK, Walther T, Scholtz S, Rudolph T, Hengstenberg C, Kempfert J, Spaziano M, Lefevre T, Bleiziffer S, Schofer J, Mehilli J, Seiffert M, Naber C, Biancari F, Eckner D, Cornet C, Lhermusier T, Philippart R, Siljander A, Giuseppe Cerillo A, Blackman D, Chieffo A, Kahlert P, Czerwinska- Jelonkiewicz K, Szymanski P, Landes U, Kornowski R, D’Onofrio A, Kaulfersch C, Søndergaard L, Mylotte D, Mehta RH, De Backer O. Incidence and outcomes of emergent cardiac surgery during transfemoral transcatheter aortic valve implantation (TAVI): insights from the European registry on Emergent Cardiac Surgery during TAVI (EuRECS-TAVI). Eur Heart J. 2017, Volume 39, Issue 8, 21 February 2018, Pages 676–684.
12. Otto CM, Kumbhani DJ, Alexander KP, Calhoon JH, Desai MY, Kaul S, Lee JC, Ruiz CE, Vassileva CM. 2017 ACC expert consensus decision pathway for transcatheter aortic valve replacement in the management of adults with aortic stenosis: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2017; 69: 1313–46.
13. Vemulapalli S, Carroll J, Mack M, Li Z, Dai D, Kosinski AS, Kumbhani DJ, Ruiz CE, Thourani VH, Hanzel G, Gleason TG, Herrmann HC, Brindis RG, Bavaria JE. Procedural volume and outcomes for Transcatheter Aortic Valve Replacement, N Eng J Med 2019;380:2541-50.

BCIS R&D Group

Literature Review January 2019

Prepared by: Michael Mahmoudi & Vijay Kunadian

Edited by Nick Curzen

 

 

CORONARY PHYSIOLOGY

 

Consistent message at 5 years from FAME 2… improved outcome by virtue of less revasc in the PCI+OMT group compared to OMT alone (but death & MI rate no different)

Five-Year Outcomes with PCI Guided by Fractional Flow Reserve

NEJM   2018; 379:250-59

The FAME-2 study has shown better 1-year clinical outcomes in patients undergoing FFR-guided PCI plus optimal medical therapy (OMT) versus OMT alone. The current manuscript provides 5-year outcomes of the study. FAME-2 had randomised 888 patients with angiographically significant coronary artery disease in whom at least one lesion was hemodynamically significant (FFR ≤ 0.80) to either FFR guided PCI plus OMT (n=447) or OMT alone (n=441). At 5 years, the PCI groups had a lower rate of the primary endpoint (a composite of death, MI, or urgent revascularization) (13.9% vs. 27%; HR 0.46; 95% CI 0.34-0.63; p<0.001). This difference was driven by a reduction in the rate of ravscularization in the PCI group (6.3% vs. 21.1%; HR 0.27; 95% CI 0.18-0.41; p=0.41). The rates of death (5.1% vs. 5.2%; HR 0.98; 95% CI 0.55-1.75) or MI (8.1% vs. 12%; HR 0.66; 95% CI 0.43-1.0) were similar in the PCI and OMT groups.

 

No significant difference in performance or drift for  SJM/Abbott or Comet BSC pressure wires in simultaneous measurements

A Randomised Controlled Trial to Compare two Coronary Pressure Wires using Simultaneous Measurements in Human Coronary Arteries The COMET trial.

EuroIntervention. 2018 Oct 30. pii: EIJ-D-18-00786. doi: 10.4244/EIJ-D-18-00786.

There is much discussion about the relative performance of pressure wires, both in terms of their diagnostic accuracy but also how much drift they exhibit. This study examined the relative performance of the new COMETÔ wire from Boston Scientific (BS), and the established technology from St Jude/Abbott Vascular (SJ), using a simultaneous readings from pairs of wires. Patients were randomised to one of three groups, BS/BS; SJ/SJ; SJ/BS. After pressure equalisation at the guide catheter, we recorded paired observations in sequence: (a) distal to proximal pressure ratio at baseline; (b) FFR at maximum hyperaemia; (c) pressure on withdrawal into the guide catheter to quantify “drift”. 106 patients were randomised, yielding 288 sets of paired recordings (BS/BS = 90; SJ/SJ = 90; SJ/BS = 108). Drift was recorded from 208 vessels (BS = 105; SJ = 103). The mean (±SD) differences for the randomised pairs were similar: BS/BS = 0.0016 (0.023); SJ/SJ = 0.002 (0.03); SJ/BS = 0.0013 (0.028). The primary outcome tested the hypothesis that the absolute magnitude of the difference (irrespective of sign) observed in the SJ/BS pairing would be similar to that in the SJ/SJ group. The median (IQR) values were SJ/BS = 0.015 (0.01-0.03); SJ/SJ = 0.01 (0.00-0.03); P = 0.61. The drift, expressed as the median (IQR) difference in Pd/Pa from 1.0 (irrespective of sign), was similar: BS = 0.02 (0.01-0.05); SJ = 0.02 (0.01-0.04); P = 0.14. There was no significant difference between these wires in terms of safety and performance, including the degree of drift.

 

 

Insights into the future…. Using physiology and virtual PCI model to predict outcome in serial or diffuse disease

Pre-Angioplasty Instantaneous Wave-Free Ratio Pullback Predicts Hemodynamic Outcome In Humans With Coronary Artery Disease. Primary Results of the International Multicenter iFR GRADIENT Registry.

JACC Cardiovasc Intv 2018; 11:757-67

Physiological assessment of serial stenoses or diffuse vessel disease may be challenging using conventional FFR. Because of the stability of resting coronary flow across a wide range of lesion severity, in tandem or diffuse disease, iFR interrogation of each lesion is theoretically permissible. iFR pullback recording may thus theoretically allow construction of a physiological map of lesion severity and thereby perhaps to predict the physiological outcome after modelling a virtual PCI. The iFR GRADIENT registry examined the accuracy of online-generated iFR-pullback curves to predict physiological outcomes post PCI and to assess the impact of these data on procedural decision-making in 123 patients undergoing PCI. Vessels protected by a graft conduit, patients with STEMI, TIMI flow grade <3, presence of clot, or lesion severity >90% by visual assessment were excluded.  The predicted post-PCI iFR calculated online was 0.93±0.05; the actual iFR was 0.92±0.06. iFR pullback predicted the post-PCI iFR with 1.4±0.5% error. As compared to angiography-guided decision-making, after iFR pullback, decision-making was changed in 31% of vessels.

 

 

Insights into the future… physiology in all coronaries calculated from your angiogram:  all the benefits of pressure wiring all vessels at the diagnostic stage, without the pressure wire?

Diagnostic performance of angiography-derived fractional flow reserve: a systematic review and Bayesian meta-analysis 

European Heart Journal, Volume 39, Issue 35, 14 September 2018, 3314–3321

Collet and colleagues sought to evaluate the diagnostic performance of FFR derived from angiography in diagnosing hemodynamically significant coronary artery disease. They undertook a systematic review and meta-analysis of studies assessing the diagnostic performance of angiography-derived FFR in 13 studies and 1842 vessels. The primary outcome was pooled sensitivity and specificity. A Bayesian bivariate meta-analysis yielded a pooled sensitivity of 89%, specificity of 90% (95% credible interval 88–92%), positive likelihood ratio (+LR) of 9.3 and negative likelihood ratio (−LR) of 0.13. The summary area under the receiver-operating curve was 0.84. The authors concluded that FFR derived from angiography was good to detect hemodynamically significant lesions compared with invasive FFR as reference. Further studies are required evaluating clinical endpoints using this technique.

 

RENAL DENERVATION

 

Renal denervation… hanging on in there & maybe ready for a come back?

Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial.

The Lancet 2018; 391:2335-45

The role of renal denervation in the treatment of hypertension has been controversial. The RADIANCE-HTN SOLO study was a multicentre, international, single-blind, randomised, sham-controlled trial undertaken in 21 US and 18 European centres. Patients were deemed eligible if they had ambulatory BP ≥ 135/85 mmHg and < 170/105 mmHg after a 4-week discontinuation of up to two antihypertensive medications. The primary efficacy endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Patients were to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded. Major adverse events included all-cause mortality, renal failure, an embolic event with end-organ damage, renal artery or other major vascular complications requiring intervention, or admission to hospital for hypertensive crisis within 30 days and new renal artery stenosis within 6 months. The study screened 803 patients and 146 eligible patients were randomised to either endovascular renal denervation (n=74) or a sham procedure (n=72). Renal denervation was associated with a greater reduction in daytime ambulatory systolic BP -8.5 mmHg vs. -2.2 mmHg; baseline adjusted difference between the groups: -6.3 mmHg; 95% CI -9.4 to -3.1; p=0.0001). No major adverse events were observed in the two groups.

Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. The

Lancet 2018; 391:2346-55

The SPYRAL HTN-ON MED study examined the safety and BP response of renal denervation in patients with uncontrolled hypertension on antihypertensive medications with regular drug adherence testing. Eligible patients had office systolic BP of between 150 mmHg-180 mmHg and diastolic BP of ≥ 90 mmHg, a 24 hour ambulatory systolic BP of between 140 mmHg-170 mmHg at a second screening and were on 1-3 antihypertensive medications. The primary efficacy endpoint was BP change from baseline based upon ambulatory BP measurements at 6 months. The study screened and enrolled 467 patients over a period of 2 years.  The results of the first 80 patients (renal denervation=38; sham control=42) are presented in this publication. Office and 24 hour ambulatory BP was lower in the denervation group (mean baseline adjusted treatment differences in 24 hour systolic BP -7.0 mmHg; 95% CI -12 to -2.1; p=0.0059; 24 hour diastolic BP -4.3 mmHg; 95% CI -7.8 to -0.8; p=0.0174; office systolic BP -4.2 mmHg; 95% CI -12.4 to -0.7; p=0.025, and office diastolic BP -4.2 mmHg; 95% CI -7.7 to -0.7; p=0.019). At 6 months, renal denervation was associated with greater reductions in office systolic BP (difference -6.8 mmHg; 95% CI -12.5 to -1.1; p=0.02), 24 hour systolic BP (difference -7.4 mmHg; 95% CI -12.5 to -2.3; p=0.005), office diastolic BP (difference -3.5 mmHg; 95% CI  -7-0; p=0.048) and 24 hour diastolic BP (difference -4.1 mmHg; 95% CI  -7.8 to -0.4; p=0.29). Medication adherence was approximately 60%. There were no major adverse events in either group.

 

ANTIPLATELET THERAPY

 

 

First trial of ticagrelor monotherapy after DES does not show benefit compared with conventional DAPT and aspirin

Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs. aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of drug-eluting stent: a multicentre, open-label, randomised superiority trial.

The Lancet 2018; 392:15-21

The optimal combination and duration of antiplatelet therapy in patients treated with DES remains uncertain. The GLOBAL LEADERS trial was designed to compare the benefits and risks of 2 years of treatment with 90mg ticagrelor twice daily (in combination with aspirin for the first month) with conventional 1-year dual antiplatelet therapy (DAPT) followed by aspirin alone in patients treated exclusively with a biolimus A9-eluting stent. The study randomised 15,968 patients with stable angina or ACS to receive either (a) aspirin 75-100mg daily plus ticagrelor 90mg twice daily for 1 month followed by 23 months of ticagrelor monotherapy or (b) standard DAPT with aspirin 75-100mg daily plus clopidogrel 75mg daily (for patients with stable angina), or ticagrelor 90mg twice daily (for ACS patients) for 12 months followed by aspirin alone for a further 12 months. The primary endpoint at 2 years was a composite of all-cause mortality or new Q-wave MI. Key secondary safety endpoints were BARC grade 3-5 bleeding. At 2 years, the primary endpoint was similar in the ticagrelor and aspirin arms (3.81% vs. 4.37%; RR 0.87; 95% CI 0.75-1.01; p=0.073). BARC grade 3-5 bleeding was also similar in the two groups (2.04% vs. 2.12%; RR 0.97; 95% CI 0.78-1.20; p=0.77).

 

The intuitive feeling that earlier potent P2Y12 inhibitor should reduce events in PPCI is still not endorsed by data!

No Benefit of Ticagrelor Pretreatment Compared With Treatment During Percutaneous Coronary Intervention in Patients With ST-Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Circ Cardiovasc Interv 2018; 11:e005528

The potential for ticagrelor preloading to provide any additional benefits in STEMI patients receiving the drug in the cath lab is controversial. Data from the SWEDEHEART registry, including 7433 patients of whom 5438 patients had received ticagrelor pretreatment prior to PPCI, has been used to study whether such an approach is associated with reductions in the composite endpoint of all-cause mortality, MI, and stent thrombosis at 30-day follow-up. In this study, crude event rates showed no difference in 30-day composite endpoint (6.2% vs. 6.5%; p=0.69), mortality (4.5% vs. 4.7%; p=0.86), MI (1.6% vs. 1.7%; p=0.72) or stent thrombosis (0.5% vs. 0.4%; p=0.80). Ticagrelor pretreatment did not increase the rate of in-hospital major bleeding rates.

 

 

Ideal duration of DAPT after ACS PCI with DES… yes, it’s still as clear as mud!

6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial.

The Lancet 2018; 391:1274-84

The debate regarding the optimal duration of dual antiplatelet therapy (DAPT) following implantation of a DES in patients presenting with an ACS remains unresolved. The SMART-DATE study was a randomised, open-label, non-inferiority trial at 31 South Korean centres that compared a strategy of either 6-month (n=1357) or 12-month or longer DAPT (n=1355) in patients presenting with unstable angina, NSTEMI, or STEMI. The primary endpoint was a composite of all-cause mortality, MI, or stroke at 18 months. Secondary endpoints included individual components of the primary endpoint, definite or probable stent thrombosis and BARC type 2-5 bleeding at 18 months. The median duration of DAPT was 6.1 months in the 6-month group and 17.7 months in the 12-month or longer group. The primary endpoint occurred 63 patients in the 6-month DAPT group and 56 patients in the 12-month or longer group (cumulative event rate 4.7% vs. 4.2%; absolute risk difference 0.5%; upper limit of one-sided 95% CI 1.8%; p_{non-inferiority}=0.03). The rates of all-cause mortality (2.6% vs. 2.9%; p=0.90), stroke 0.8% vs. 0.9%; p=0.84), stent thrombosis (1.1% vs. 0.7%; p=0.32), and bleeding (2.7% vs. 3.9%; p=0.09) were similar in both groups. MI was more common in the 6-month group (1.8% vs. 0.8%; p=0.02). Based upon the increased risk of MI and the wide non-inferiority margin, the study has recommends prolonged DAPT in ACS patients undergoing PCI with DES.

 

De-escalating from prasugrel to clopidogrel guided by platelet function testing in ACS PCI patient <70 improves outcome… but not in the older age group

Age and outcomes following guided de-escalation of antiplatelet treatment in acute coronary syndrome patients undergoing percutaneous coronary intervention: results from the randomized TROPICAL-ACS trial 

European Heart Journal, Volume 39, Issue 29, 1 August 2018, 2749–2758,

Our population is ageing with consequent increase in cardiovascular disease burden and co-morbidities. Often strategies that work in younger patients have not been proven to be beneficial in older patients. The older patients are often classified as high bleeding risk patients and therefore a gentler approach to antiplatelet therapy post PCI might be an attractive strategy. To prove this, the authors of the above trial studied the impact of age on clinical outcomes following de-escalation of antiplatelet treatment in ACS patients undergoing PCI. Patients were randomly assigned in a 1:1 fashion to either standard treatment with prasugrel for 12 months (control group) or to a guided de-escalation regimen (1 week prasugrel followed by 1 week clopidogrel and platelet function testing guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). In younger patients (age ≤70 years, n = 2240), the occurrence of cardiovascular death, myocardial infarction, stroke, or bleeding ≥ grade 2 according to the BARC criteria at 1 year was significantly lower in guided de-escalation vs. control group [5.9% vs. 8.3%; P = 0.03]. In elderly patients (age >70 years, n = 370), the absolute risk of events was higher without significant differences between guided de-escalation vs. control group (15.5% vs. 13.6%; P = 0.56). The authors concluded that the treatment effects of guided de-escalation for P2Y₁₂ inhibitors is different between young and elderly patients. The net clinical benefit seen in younger patients was not seen in older patients. This study of course is limited by small sample size and will need to be evaluated further in larger studies.

 

STRUCTURAL/VALVE INTERVENTION

 

 

A new low frequency worm of concern about coronary obstruction after TAVI?

Delayed Coronary Obstruction After Transcatheter Aortic Valve Replacement.

JACC 2018; 71:1513-24

The incidence and outcome of delayed coronary obstruction (DCO) following TAVI are unknown. Retrospective data analysis from an international multicentre registry, including 17,092 patients, has demonstrated that DCO has an incidence of 0.22%, and commonly occurred between 1-7 days after the procedure. DCO was more common after valve-in-valve implantation (0.89% vs. 0.18%; p<0.001) and with self-expandable valves (0.36% vs. 0.11% (balloon expandable); p<0.001). The most common presentation was with cardiac arrest (31.6%) followed by STEMI (23.7%), with PCI being the most common treatment strategy. The left coronary artery was obstructed in 92.1% of cases. The in-hospital death rate was 50%, and was greater if DCO occurred within 7 days of the procedure.

 

 

Local anaesthetic for TF TAVI is quicker with shorter hospital stay with no cost in terms of outcome…. Going, going, GONE!

Comparison of general anaesthesia and non-general anaesthesia approach in transfemoral transcatheter aortic valve implantation

Heart 2018. Oct;104(19):1621-1628.

In the UK TAVI registry, the authors studied the impact of GA versus LA on procedural outcomes and 30-day and 1-year mortality in TF TAVI procedures using either an Edwards Sapien or a Medtronic CoreValve prosthesis. Propensity score-matching analysis was performed to adjust for confounding factors. 2243 patients were studied (aged 81.4±7.5 years, 1195 males). 81% underwent TAVI with GA and 19% without GA. Transoesophageal echocardiography (TOE) was used in 92.3% of GA and 12.4% of non-GA cases (p<0.001). There was no significant difference in the rate of successful valve deployment (GA 97.2% vs non-GA 95.7%, p=0.104) and in the incidence of more than mild aortic regurgitation at the end of the procedure (GA 5.6% vs non-GA 7.0%, p=0.295). Procedure time was longer (131±60 vs 121±60mins, p=0.002) and length of stay was greater (8.0±13.5 vs 5.7±5.5 days, p<0.001) for GA cases with no difference in 30-day and 1-year mortality rates did not differ between the groups. The authors concluded that procedure outcome, and 30-day and 1-year mortality are not influenced by mode of anaesthesia albeit GA was associated with longer procedure duration and greater length of stay.

 

Promising results for balloon expandable mitral valve… would be really interesting to see the outcome in lower risk patients?

Clinical and haemodynamic outcomes of balloon-expandable transcatheter mitral valve implantation: a 7-year experience

European Heart Journal, Volume 39, Issue 28, 21 July 2018, 2679–2689,

Percutaneous approaches to treat mitral valve disease are the subject of much interest and research. In this study, the authors evaluated the early and long-term clinical and haemodynamic outcomes of balloon-expandable transcatheter mitral valve implantation (TMVI). Patients were followed at 1 month, 1 year, and yearly thereafter. A total of 91 patients (median age 73; 70% female) at high risk for surgery with a median EuroSCORE II of 9.6 (4.0–14.6)% underwent TMVI. Indication for TMVI was bioprosthesis failure (valve-in-valve) in 37.3%, annuloplasty failure (valve-in-ring) in 33.0%, and severe mitral annulus calcification (MAC) in 29.7%. The transseptal approach was used in 92.3% of patients with technical success of 84.6% of patients and the mean transmitral gradient decreased from 9.3 ± 3.9 mmHg at baseline to 6.0 ± 2.3 mmHg at discharge (P < 0.001). At 30 days, 7.7% of patients had died, without significant differences between groups, and a major stroke occurred in 2.2% of patients. The cumulative rates of all-cause mortality at 1-year and 2-year follow-up were 21.0% and 35.7%, with a higher late mortality in patients with annular calcification. At 6 months to 1 year, 68.9% of patients were in NYHA Class I/II, and 90.7% of patients had mild or less mitral regurgitation. The authors concluded that transcatheter mitral valve implantation using balloon-expandable valves in selected patients was associated with a low rate of peri-procedural complications and acceptable long-term outcomes.

 

MULTIVESSEL DISEASE/ PCI V CABG

 

Is PCI really equivalent to CABG in complex MV disease?

Mortality after coronary artery bypass grafting versus percutaneous coronary intervention with stenting for coronary artery disease: a pooled analysis of individual patient data.

The Lancet 2018; 391:939-48

The mortality benefit of CABG over PCI remains debatable. The authors have undertaken a meta-analysis of 11 randomised studies, including 11,518 patients assigned to PCI (n=5,753) or CABG (5,765) with multivessel or left main disease who did not present with acute MI and who had more than 1-year follow-up for all-cause mortality. PCI was undertaken with BMS or DES. Mean SYNTAX score was 26, with 22.1% of patients having a SYNTAX score of ≥33. As compared to CABG, PCI was associated with greater 5-year all-cause mortality (11.2% vs. 9.2%; HR 1.20; 95% CI 1.06-1.37; p=0.0038). Further breakdown of the data has indicated that 5-year all cause mortality was significantly greater with PCI in patients with multivessel disease (11.5% vs. 8.9%; HR 1.28; 95% CI 1.09-1.49; p=0.0019) including those with diabetes (15.5% vs. 10%; HR 1.48; 95% CI 1.19-1.84; p=0.0004). In patients with left main disease, 5-year all-cause mortality was similar with PCI and CABG regardless of the diabetic status and SYNTAX score (10.7% vs. 10.5%; HR 1.07; 95% CI 0.87-1.33; p=0.52).

 

Multivessel PCI can be equally successful if either done in a single session or staged

Single-session versus staged procedures for elective multivessel percutaneous coronary intervention

Heart 2018 Jun;104(11):936-944

Toyoto et al studied the effect of single-session multivessel percutaneous coronary intervention (PCI) strategy versus staged multivessel strategy on clinical outcomes in patients with stable coronary artery disease or NSTEMI in the Kyoto PCI/CABG cohort 2 registry in 2018 patients. All-cause death, myocardial infarction and stroke at 5-year follow-up were the primary outcome. 35% patients underwent single-session multivessel PCI and 65% had staged multivessel PCI. Though the 30-day incidence of all-cause death was significantly higher in the single-session group than in the staged group (1.1% vs. 0.2%, p=0.009), the causes of death in 11 patients who died within 30 days were generally not related to the procedural complications. The 5-year primary outcome was not different between the 2 groups (p=0.45). For the subgroup analyses including age, gender, extent of CAD, severe chronic kidney disease and heart failure, there was no significant interaction between the subgroup factors and the effect of the single-session strategy versus the staged strategy for the primary outcome measure. The authors concluded that single-session multivessel PCI strategy was associated with at least comparable 5-year clinical outcomes compared with the staged multivessel PCI.

 

Useful to know, but rocket science this ain’t

Prior Percutaneous Coronary Intervention and Mortality in Patients Undergoing Surgical Myocardial Revascularization. Results From the E-CABG (European Multicenter Study on Coronary Artery Bypass Grafting) With a Systematic Review and Meta-Analysis.

Circ Cardiol Intv 2018; 11:e005650

The clinical implications of PCI in patients who subsequently require CABG are uncertain. Data from the prospective European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) including 3641 patients of whom 685 patients had previously undergone PCI has shown that prior PCI was not associated with increased hospital mortality (OR 0.90; 95% CI 0.39-2.08; p=0.81). Prior PCI was not shown to have any impact upon hospital morbidity and mortality, blood transfusions, hospital resource use, or neurological/renal/cardiac complications.

 

MISCELLANEOUS

 

Reassurance from UK dataset that left radial approach is at least as safe as right radial…. Or perhaps even safer??

Incidence, Determinants, and Outcomes of Left and Right Radial Access Use in Patients Undergoing Percutaneous Coronary Intervention in the United Kingdom. A National Perspective Using the BCIS Dataset.

JACC Cardiovasc Intv 2018; 11:1021-33

The right radial route (RRR) has become the most common route for coronary intervention in many European countries. The left radial route (LRR) is occasionally used in patients with previous CABG as well as patients in whom anatomical considerations preclude the use of the RRA. Data from the BCIS database has been used to compare RRR and LRR with regards to in-hospital or 30-day mortality, MACE, in-hospital stroke, and major bleeding complications between 2007-2014. The study included 342,806 cases with 96% in the RRA group and 4% in the LRR group. As compared to the RRR, the LRR was not associated with significant differences in in-hospital mortality (OR 1.19; 95% CI 0.90-1.57; p=0.20), 30-day mortality (OR 1.17; 95% CI 0.93-1.74; p=0.16), MACE (OR 1.06; 95% CI 0.86-1.32; p=0.56) or major bleeding (OR 1.22; 95% CI 0.87-1.77; p=0.24). In propensity match analysis, LRR was associated with a significant decrease in in-hospital stroke (OR 0.52; 95% CI 0.37-0.82; p=0.005).

 

Drug-coated balloons in de novo lesions in small vessels… another niche?

Drug-coated balloons for small coronary artery disease (BASKET-SMALL 2): an open-label randomised non-inferiority trial.

The Lancet 2018; 392:849-56

Drug-eluting balloons (DEB) have emerged as a realistic treatment strategy for in-stent restenosis but their role in the treatment of de novo CAD remains controversial. The BASKET-SMALL 2 trial examined the non-inferiority of DEB (SeQuent Please, B Braun Melsungen AG, Germany) versus the everolimus-eluting Xience stent in 758 patients (DEB=382, Xience=376) with de novo lesions < 3mm in diameter. Patients included those with ACS, stable angina, or evidence of silent ischemia. The primary endpoint was the non-inferiority of DEB versus Xience with regards to MACE as defined by cardiac death, non-fatal MI, and TVR after 12 months. The non-inferiority margin was set as an absolute difference of 4% in MACE. Non-inferiority was demonstrated as the 95% CI of the absolute difference was below the predefined margin (-3.83 to 3.93%; p=0.022). At 12 months, the DEB and Xience groups had similar MACE rates in the full analysis population (7.5% vs. 7.3%; HR 0.97; 95% CI 0.58-1.64; p=0.92).

 

Does  a biodegradable polymer really make any difference at all in DES?  Another study shows no harm or benefit?

Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting, biodegradable polymer coronary stent (TARGET ALL Comers): a multicentre, open-label, randomised non-inferiority trial.

The Lancet 2018; 392:1117-26

The biodegradable polymer concept, although attractive in theory, has remained an enigma in the field of PCI. The TARGET ALL Comers study was a multicentre, open-label, randomised non-inferiority trial comparing the FIREHAWK DES (n=823) with its fully biodegradable sirolimus-containing polymer versus the Xience DES (n=830). The primary endpoint was target lesion failure (TLF) at 12 months, defined as a composite of cardiac death, target vessel MI< or ischemia driven TLR. Late lumen loss was the primary endpoint of an angiographic substudy. At 12 months, TLF was 6.1% in the FIREHAWK group and 5.9% in the Xience group (difference 0.2%; 90% CI -1.9 2.2; p_{non-inferiority}=0.004; 95% CI -2.2 to 2.6; p_superiority =0.88). The rates of stent thrombosis and ischemia driven revascularization were similar in the two groups. Late lumen loss in the angiographic substudy were also favourable (0.17mm for FIREHAWK vs. 0.11mm for Xienec; p=0.48; absolute difference 0.05 mm; 95% CI -0.09 to 0.18; p_{non-inferiority}=0.024).

No prognostic benefit to CTO PCI in patients presenting with STEMI… but ultimately less angina.  Shouldn’t we leave the CTO alone  and then wait to see who develops angina, then?

Long-term impact of chronic total occlusion recanalisation in patients with ST-elevation myocardial infarction.

Heart 2018 Sep;104(17):1432-1438

To treat or not to treat a CTO in the setting of a STEMI is a common clinical conundrum given concurrent CTO is found in 10% of patients with STEMI. The authors determined mid-term and long-term clinical outcome of CTO-PCI versus CTO-No PCI in 302 STEMI patients after successful primary PCI. Patients were randomised to either CTO-PCI or CTO-No PCI. Cardiac death, coronary artery bypass grafting and MI consisted of the primary outcome (MACE). Other end points were 1-year left ventricular function (LVF); LV-ejection fraction and LV end-diastolic volume and angina status. At a median follow-up of 3.9 years MACE was not significantly different between arms (13.5% vs. 12.3%, P=0.93). Cardiac death was more frequent in the CTO-PCI arm (6.0% vs 1.0%, P=0.02) with no difference in all-cause mortality (12.9% vs. 6.2%, HR 2.07, P=0.11). One-year LVF did not differ between both arms. However, there were more patients with freedom of angina in the CTO-PCI arm at 1 year (94% vs. 87%, P=0.03). In this randomised trial involving STEMI patients with a concurrent CTO, CTO-PCI was not associated with a reduction in long-term MACE compared to CTO-No PCI albeit with more patients free of angina in the CTO-PCI group.

 

A more sinister side to a condition we are now a bit blasé about?   Takotsubo bites back

Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy.

Circulation  2018; 137:1039-1048

Despite normalization of the resting LV ejection fraction following an episode of Takotsubo cardiomyopathy (TCM), the long-term manifestations of this clinical entity has been poorly investigated. An observational case-control study of 37 patients with prior (range 13-39 months) TCM and 37 age- & gender-matched controls has examined long-term clinical and functional consequences of TCM using serum biomarkers, cardiopulmonary exercise testing, echocardiography, and CMR including ³¹P-spectroscopy.  In this study 97% of participants were female, 88% had symptoms compatible with heart failure and limitation on exercise testing (reduced peak oxygen consumption 24±1.3 vs. 31±1.3 ml/Kg/min, p<0.001; increased VE/V_CO2 slope 31±1 vs. 26±1; p=0.002). Furthermore, TCM patients had impaired cardiac deformation indices (apical circumferential strain -16±1 vs. -23±1.5%; p<0.001; global longitudinal strain -17±1 vs. -20±1%; p=0.006), increased T1 mapping values (1264±10 vs. 1184±10 ms; P<0.001) and impaired cardiac energetic status (phosphocreatine:∂-adenosine triphosphate ratio 1.3±0.1 vs. 1.9±0.1; p<0.001).

 

Fascinating insight into the potential benefit of CTCA as the front line test for stable chest pain….  FORECAST looms!

The SCOT-HEART Investigators. Coronary CT Angiography and 5-Year Risk of Myocardial Infarction.

NEJM 2018; 379:924-33

The long-term clinical impact of CT coronary angiography (CTCA) in the assessment of patients with stable chest pain is uncertain. The SCOT-HEART investigators examined the rates of death from coronary artery disease or non-fatal MI at 5-years in 4146 patients with stable chest pain who had been referred to a cardiology clinic for further evaluation and who were randomized to either CTCA plus standard care (n=2073) or standard care alone (n=2073). The 5-year rate of the primary endpoint was significantly lower in the CTCA group (2.3% vs. 3.9%; HR 0.59; 95% CI 0.41-0.84; p=0.004), driven by a lower rate of nonfatal MI in the CTCA group (HR 0.60; 95% CI 0.41-0.87). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTCA group in the first few months of follow-up, the overall rates were similar in the two groups (HR 1.0; 95% CI 0.88-1.13 for invasive angiography and HR 1.40; 95% CI 1.19-1.65 for revascularization). The observed results may in part be explained by the CTCA group having more preventive therapies (odds ratio 1.40; 95% CI1.19-1.65) and more antianginal therapy (odds ratio 1.27; 95% CI 1.05-1.54).

 

The final nail in the coffin for for aspirin as a primary prevention treatment in patients without CV disease?

Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly.

NEJM  2018 Online

The role of aspirin in primary prevention has remained controversial particularly given the increased risk of bleeding. The ASPREE trial randomized 19,114 men and women aged 70 years or older (≥65 years amongst blacks and Hispanics in the US) to receive either aspirin 100mg/day (n-9525) or placebo (n=9589). Participants did not have any evidence of cardiovascular disease, dementia, or disability. The prespecified secondary endpoint reported in this publication included major haemorrhage, and cardiovascular disease defined as fatal coronary heart disease, non-fatal MI, fatal or nonfatal stroke, or hospitalization for heart failure. After a median of 4.7 years follow-up, both the aspirin and placebo group had similar rates of cardiovascular disease (10.7 vs. 11.3 events per 1000 person-years; HR 0.95; 95% CI 0.83-1.08). Aspirin was associated with greater rates of major haemorrhage (8.6 vs. 6.2 events per 1000 person-years; HR 1.38; 95% CI 1.18-1.62; p<0.001).

Wearable vest may not fill the gap between the index acute Mi and the recommended time to reassess and consider ICD

Wearable Cardioverter-Defibrillator after Myocardial Infarction.

NEJM   2018; 379:1205-15

The optimal timing of implanting an ICD in patients with severe LV systolic dysfunction secondary to a MI is controversial with two previous studies showing no long-term mortality benefit from ICDs that had been implanted immediately after a MI. The VEST randomised trial examined the efficacy of a wearable ICD during the period before ICDs are currently recommended (40-90 days after MI) in patients who have had a MI and ejection fraction ≤35%. Eligible patients were randomised in a 2:1 ratio to either the Zoll LifeVest ICD and guideline directed medical therapy (n=1524) or guideline directed medical therapy alone (n=778). The primary endpoint was the composite of sudden death or death from ventricular tachyarrhythmia at 90 days. Secondary outcomes included death from any cause and nonarrhythmic death. The rates of arrhythmic death (1.6% vs. 2.4%; RR 0.67; 95% CI 0.37-1.21; p=0.18) and non-arrhythmic death (1.4% vs. 2.2%; RR 0.63; 95% CI 0-33-1.19; uncorrected p=0.15) were similar in the device/medical therapy and medical therapy alone groups. Death from any cause was lower in the ICD group (3.1% vs. 4.9%; RR 0.64; 95% CI 0.43-0.98; uncorrected p=0.04).

 

Attrition after vein graft pci not halted by DES versus BMS… ?surprising, or inevitable

Efficacy Over Time With Drug-Eluting Stents in Saphenous Vein Graft Lesions.

JACC  2018; 71:1973-82

The “Is Drug-Eluting-Stenting Associated with Improved Results in Coronary Artery Bypass Grafts” (ISAR-CABG) trial has indicated that DES were associated with superior clinical outcomes compared to BMS at 1-year follow-up. The current manuscript reports 5-year results of the study. ISAR-CABG randomised 610 patients with ≥50% de novo stenosis of a SVG to treatment with a DES (n=303) or a BMS (n=303). The primary endpoint was the combined incidence of death, MI, or TLR. Secondary endpoints were the composite of death or MI and TLR. At 5 years, the primary endpoint was similar between the DES and BMS groups (55.5% vs. 53.6%; p=0.89). Death or MI were also similar between the DES and BMS groups (32.8% vs. 36.6%; p=0.24), as were the rates for TLR (33.1% vs. 25.5%; p=0.27). 

Routine oxygen in PPCI patients has no benefit if they are normoxemic… other data show harm for O2 in these patients

Oxygen therapy in ST-elevation myocardial infarction

European Heart Journal, Volume 39, Issue 29, 1 August 2018, 2730–2739,

This study was conducted to determine whether supplemental oxygen in patients with STEMI impacts on procedure-related and clinical outcomes. The DETO2X-AMI trial randomized patients with suspected MI to receive oxygen at 6 L/min for 6–12 h or ambient air. In total, 2807 patients undergoing PPCI for STEMI were included (1361 received oxygen, vs. 1446 received ambient air). The prespecified primary composite endpoint of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis at 1 year occurred in 6.3% vs. 7.5% (oxygen versus ambient air P = 0.27). There was no difference in the rate of death from any cause (P = 0.41), rate of rehospitalization for MI (P = 0.73), rehospitalization for cardiogenic shock (P = 0.95), or stent thrombosis (P = 0.64). Routine use of supplemental oxygen in normoxemic patients with STEMI undergoing primary PCI did not significantly affect 1-year all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis

BCIS R&D Group

Literature Review January 2020

Prepared by: Michael Mahmoudi, Julian Gunn, Paul Morris & Aung Myat

 

STABLE CAD & ACS

 

Benefits of complete revascularization in STEMI patients are long lasting

Long-term follow-up of complete versus lesion-only revascularization in STEMI and multivessel disease. The CvLPRIT Trial.

JACC 2019; 74:3083-94
Multivessel coronary artery disease (CAD) may be present in up to 50% of patients presenting with STEMI. In such patients, there is increasing evidence that complete revascularization of both the infarct related artery (IRA) and non-culprit lesion(s) either at the time of PPCI or within a relatively short time frame of the index procedure will provide prognostic benefits. The CvLPRIT (Complete Versus Lesion-Only Primary PCI Trial) is the first study to provide data regarding the long-term efficacy of such an approach. The original study recruited 296 patients, with 150 randomized to complete revascularization (CR), and 146 randomized to IRA-only PCI. At a median follow-up of 5.6 years, the primary MACE (all-cause death, MI, heart failure, and ischemia-driven revascularization) endpoint was lower in the CR group (24% vs. 37.7%; HR: 0.57; 95% CI: 0.37-0.87; p=0.0079). The composite endpoint of all cause death/MI was lower in the CR group (10% vs. 18.5%; HR: 0.47; 95% CI: 0.25-0.89; p=0.0175). In a landmark analysis from 12 months to final follow-up, there was no significant difference between MACE, death/MI, and individual components of the primary endpoint suggesting that the majority of the benefits occurred in the early phase and was maintained during longer-term follow-up. It is noteworthy that the vast majority of new revascularization that occurred between 12 months and long-term follow-up in the IRA group were located in the original non-IRA lesion.

 

Left main PCI remains the Achilles heel of interventional cardiology

Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised non-inferiority NOBLE trial

Lancet 2020; 395:191-199
Hot on the heels of EXCEL reporting its 5-year outcomes in September 2019, the NOBLE trial published its own 5-year results in December 2019. In brief, NOBLE was a prospective, randomised, open-label, non-inferiority trial which randomised patients 1:1 with left main coronary artery disease (LMCAD) to either PCI or CABG. Patients were recruited from 36 centres in northern Europe, whereas EXCEL recruited from Europe, North and South America, and the Asia Pacific region. EXCEL also recruited patients with low to moderate anatomic complexity (SYNTAX score ≤32), whereas NOBLE did not stipulate a SYNTAX score level of complexity but instead recruited patients with left main lesions visually assessed as >50% or ≤0.80 by fractional flow reserve in the ostium, mid-shaft, or bifurcation, with no more than 3 additional complex lesions (i.e. CTOs, bifurcation lesions needing a 2-stent strategy or lesions with calcified or tortuous vessel morphology). At 3 years, the primary composite endpoint of MACCE (consisting of all-cause mortality, non-procedural MI, any repeat coronary revascularisation, and stroke) were 28% for PCI (121 events) and 18% for CABG (80 events), HR 1.51 (95% CI 1.13-2.00), exceeding the limit for non-inferiority, with CABG shown to be significantly better than PCI (p=0.0044). At 5 years, the Kaplan-Meier estimates of MACCE were 28% (165 events) for PCI and 19% (110 events) for CABG, HR 1.58 (95% CI 1.24-2.01). The difference was driven by significantly higher rates of non-procedural MI (p=0.0002) and repeat revascularisation (p=0.0009) seen in the PCI arm. Therefore CABG was again found to be superior for the primary composite endpoint (p=0.0002).
How prognostically significant is repeat revascularization as an endpoint in this context? EXCEL did not include ischemia driven revascularization (IDR) as a component of the primary endpoint. The principal investigators considered IDR undeserving of parity with critical outcomes such as death, stroke or extensive MI. The justification being repeat revascularization was of no greater clinical consequence than many other adverse perioperative outcomes that would have favoured PCI (when compared to CABG), such as major bleeding, acute kidney injury, arrhythmia, or serious wound infection. Indeed, without repeat revascularization as the major driving force, PCI would have reached equipoise with CABG for the management of symptomatic LMCAD in the NOBLE trial. Moreover, patients may be more willing to accept the likelihood of a repeat percutaneous intervention in the medium to long term over the invasive nature of CABG and the inherently higher risk of perioperative complications. NOBLE also excluded peri-procedural MI from its primary endpoint despite general acceptance that the prognostic implications of an MI tend not to be predicated by when it occurs, but the territorial extent to which it occurs. Greater harmonisation of individual and combined endpoint definitions for future trials is required.

 

The lipid content of coronary lesions may be a novel marker of vulnerability

Identification of patients and plaques vulnerable to future coronary events with near-infrared spectroscopy intravascular ultrasound imaging, a prospective cohort study

Lancet 2019; 394:1629-1637
The desire to accurately detect vulnerable plaques in non-obstructed coronary arteries and be able to predict their likelihood of causing a major adverse cardiovascular event has long been seen as the Holy Grail of interventional cardiology. Identification of thin cap fibroatheroma (TCF) was previously regarded as the most likely substrate for vulnerable plaques. Attempts to image TCF using intravascular ultrasound (IVUS) have, however, been hampered by its inability to identify lipid core and the need for high-level core laboratory support. Focus has thus shifted to detection of lipid-rich plaques (LRP), which are known to cause the majority of coronary deaths from autopsy studies. Near-infrared spectroscopy (NIRS) has been developed to impart unique spectral differences between cholesterol and collagen to readily differentiate LRP from normal vessels or fibrotic and calcified plaques. It is incorporated with IVUS in a dual modality probe, allowing simultaneous analysis of structure and plaque composition. NIRS provides both a graphical result as a yellow area on a red background and a numerical value to indicate LRP size (known as the Lipid Core Burden Index which has a maximum level of 4mm [maxLCBI4mm]). According to previous validation studies, a maxLCBI4mm of >400 is associated with vulnerable plaque causing MI. NIRS is FDA approved.
The LRP study enrolled 1563 patients with suspected CAD proceeding to cardiac catheterization ± PCI and scanned non-culprit lesion segments using NIRS-IVUS. Patient- and plaque-level hierarchical hypotheses were set, each assessing the association between maximum LCBI4mm with non-culprit major adverse cardiovascular events (NC-MACE). Of the 1271 patients with evaluable LCBI4mm, the mean number of arteries scanned per patient was 2.1 with ≥50 mm of eligible vessel in 89% (1135/1271) of patients. Over a 2-year follow-up, the cumulative incidence of NC-MACE was 9%. In patients with max LCBI4mm >400, the unadjusted hazard ratio (HR) was 2.18 (95% CI 1.48–3.22; p<0.0001) and adjusted HR was 1.89 (1.26–2.83; p=0.0021) on a patient level. On a plaque level for segments with a max LCBI4mm > 400, the unadjusted HR increased to 4.22 (95% CI 2.39–7.45; p<0.0001) and the adjusted HR to 3.39 (1.85–6.20; p<0.0001). There were few periprocedural complications (<0.5%). The LRP study is the largest prospective intracoronary imaging study to demonstrate that NIRS-IVUS is a safe and clinically user-friendly tool to appropriately identify patients and coronary segments at greater risk of future adverse coronary events.
But how do we use this information? On a patient level it might identify individuals that require a more intensive lipid-lowering regime and may stimulate greater focus on lifestyle modification. On the other hand such information could be incendiary to a patient that might now feel they are walking around with a ticking time bomb. Good communication will be essential in this scenario. On a plaque-level, prophylactic stenting of vulnerable segments in the absence of haemodynamic compromise may do more harm than good. We await the results of the PROSPECT II (NCT02171065) and PREVENT (NCT02316886) randomised studies comparing optimal medical therapy versus focal stenting plus optimal medical therapy to reduce NC-MACE using IC imaging.

 

Colchicine as a novel, inexpensive secondary prevention therapy post MI?

Efficacy and safety of low-dose colchicine after myocardial infarction.

NEJM 2019; 381:2497-2505
Inflammation is thought to play a central role in the pathogenesis of atherothrombosis. Although pharmacological therapy for secondary prevention (eg. aspirin and statins) appear to have salutary effects on inflammation, the identification of an effective anti-inflammatory agents has remained elusive. The COLCOT investigators evaluated the effects of low dose colchicine (0.5mg OD) on cardiovascular outcomes as well as its long-term safety profile in 4745 patients recruited within 30 days after a MI. The primary efficacy endpoint was a composite of death from cardiovascular causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization. After a median follow-up of 22.6 months, the primary endpoint was lower in the colchicine group than the placebo group (5.5% vs. 7.1%; HR: 0.77; 95% CI: 0.61-0.96; p=0.02). This result was driven predominantly by lower risks for angina and stroke. A significant effect on death from cardiovascular causes or MI was not shown. Overall, the incidence of adverse events was similar in the two groups; however, some gastrointestinal side effects such as nausea were more frequent in the colchicine group as were pneumonias. Of note, 1.9% of the patients were lost to follow-up, 0.6% withdrew consent, and nearly 19% of the patients in both treatment groups stopped receiving colchicine or placebo prematurely. These factors may have obscured the true cardiovascular treatment effect or adverse-event profile.

 

Gender disparity in NSTEMI patients

Outcomes of Women Compared With Men After Non–ST-Segment Elevation Acute Coronary Syndromes.

JACC 2019; 74:3013-22
Women present with CAD at a later age and with a higher burden of comorbidities than men. They are also more likely to present with atypical symptoms and less likely to be treated with guideline-directed medical therapy. Ten TIMI trials including 68,730 patients with NSTEMI, 29% of whom were women, sought to determine whether outcomes differed between women and men after NSTEMI and if any observed differences were due to differences in baseline comorbidities, treatment strategies, or if gender itself was associated with the risk of cardiovascular events during follow-up.
In this study women were older and more frequently had hypertension, diabetes, previous heart failure, and renal disease than men. Women were at similar risk of MACE (CV death, MI, or stroke) compared with men (HR: 1.04; 95% CI 0.99-1.09; p=0.16) but at higher risk of all-cause death (HR: 1.12; 95% CI: 1.01-1.24; p=0.03). After adjustment for baseline differences, risks of MACE ( HR: 0.93; 95% CI: 0.88-0.98; p<0.01) and all-cause death (HR: 0.84; 95% CI: 0.78-0.90; p<0.0001) were lower among women than men.

 

PHYSIOLOGY & IMAGING

 

Moving beyond coronary stenosis in patients with stable chest pain

1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CoerMicA)

JACC Cardiovasc Interv 2020; 13:33-45
Approximately 50% of patients presenting with stable chest pain may not have significant epicardial coronary stenosis. Coronary microvascular dysfunction has emerged as an important diagnosis in such patients and is associated with an increased risk of MACE independently of conventional risk factors.
The CorMicA trial involving 151 patients with ischemia and no obstructive coronary disease found that an interventional diagnostic procedure (IDP) to rule in or rule out a disorder of coronary vasomotion was feasible and resulted in improved anginal symptoms at 6 months in patients whose IDP results were disclosed compared to the blinded control group. Results at 1 year have shown that the intervention group had improvements in angina by 27% (difference 13.6 units; 95% CI: 7.3-19.9; p<0.001) and EQ-5D index (mean difference 0.11 units; 95% CI: 0.03-0.19; p=0.1). After a median follow-up of 19 months, MACE (mortality, MI, unstable angina, heart failure hospitalization and cerebrovascular events) were similar in both groups (12% vs. 11%; p=0.8).

 

FFR based deferral of coronary revascularization remains a safe practice

Two-Year Outcomes After Deferral of Revascularization Based on Fractional Flow Reserve
The J-CONFIRM Registry

Circ Cardiovasc Interv 2020; e008355
There is overwhelming evidence in support of FFR-guided revascularization. Whether deferral of coronary lesions with FFR<0.80 is safe in real world practice is less clear cut. The J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicentre Registry) prospectively enrolled 1263 patients with 1447 lesions in whom revascularization was deferred based on FFR. The primary endpoint was the cumulative 2-year incidence of target vessel MI and clinically driven TVR. The mean FFR was 0.86±0.06. At 2 years, target vessel failure rate was 5.5% in deferred lesion, driven by a 5.2% rate of clinically driven TVR. The rates of cardiac death and target vessel related MI was 0.41% and 0.41% respectively. Independent predictors of 2-year target vessel failure were FFR value (per 0.01 decrease; HR: 1.07; 95% CI: 1.04-1.11; p<0.001), left main lesion (HR: 5.89; 95% CI: 2.72-12.8; p<0.001), Moderate to severe calcific lesions (HR: 2.49; 95% CI: 1.36-4.58; p=0.003), haemodialysis (HR: 2.9; 95% CI: 1.11-7.58; p=0.03), and right coronary artery lesion (HR: 1.78; 95% CI: 1.02-3.11; p=0.042).

 

Even More data for deferral of coronary lesions

Outcomes with Deferred Versus Performed Revascularization of Coronary Lesions with Gray-Zone Fractional Flow Reserve Values

Circ Cardiovasc Interv 2019;12:e008315
The management of coronary lesions with FFR values in the gray zone (0.75-0.80) has remained debateable. A meta-analysis of 7 observational studies including 2683 patients comparing a strategy of deferred versus performed revascularization of coronary lesions with gray zone FFR values has reported similar rates of MACE (12.54% vs. 11.25%; OR: 1.64; 95% CI: 0.78-3.44; p=0.19), cardiac mortality (1.25% vs. 0.72%; OR: 1.78; 95% CI: 0.58-5.46; p=0.31), and MI (1.28% vs. 2.66%; OR: 0.79; 95% CI: 0.22-2.79; p=0.71). Deferral of revascularization was associated with a higher incidence of TVR (9.12% vs. 5.78%; OR: 1.85; 95% CI: 1.03-3.33; p=0.04).

 

IC or IV Adenosine-Route does not matter

Individual Lesion-Level Meta-Analysis Comparing Various Doses of Intracoronary Bolus Injection of Adenosine with Intravenous Administration of Adenosine for Fractional Flow Reserve Assessment

Circ Cardiovasc Interv 2020; e007893
The current literature is modestly sized and inconclusive with regards to the equivalence of intravenous (IV) versus intracoronary (IC) adenosine for FFR measurement. A lesion-level meta-analysis including 1972 FFR measurements and 1413 lesions comparing IC and IV (140 μg/kg) from 16 studies has shown a strong correlation (correlation coefficient=0.915; p<0.001) between IC-FFR and IV-FFR. Mean FFR was 0.81±0.11 for IC adenosine and 0.81±0.11 for IV adenosine (p<0.001). A non-clinically relevant mean difference of 0.006 between the two methods were noted. When stratified by the IC adenosine dose, mean difference between IC and IV-FFR were 0.004, 0.011, 0r 0.000 FFR units for low dose (<40μg), intermediate dose (40-99μg) and high dose (100μg) IC adenosine respectively.

 

IMR remains the gold standard for assessment of microvascular function

Pressure-bounded coronary flow reserve to assess the extent of microvascular dysfunction in patients with ST-elevation acute myocardial infarction

EuroIntervention 2019 Dec 24. doi: 10.4244/EIJ-D-19-00674
The importance of microvascular function in both stable and ACS patients is increasingly recognised. In patients with STEMI, elevated microvascular resistance is associated with increased infarct size, complication rates, and adverse prognosis. Given the limitations of current indices of microvascular function (including time and cost), the current study examined whether ‘pressure-bound coronary flow reserve’ (pb-CFR) defined as the interval between the minimum and the maximum possible CFR values would represent a simpler and quicker way for assessing microvascular function at the time of PPCI. In addition to pb-CFR, IMR and CFR were measured with a pressure and temperature sensitive wire. Coronary physiological indices were measured in the infarct-related artery before and /or post-PPCI. Cardiac MRI was performed at 48 hours and six months. In 148 STEMI patients, pb-CFR improved with PCI, was predictive of myocardial injury at 48 hours, demonstrated an association with IMR and was also mildly predictive of microvascular obstruction. However, it was not predictive of LV ejection fraction. IMR outperformed both pb-CFR and CFRthermo in predicting all the key outcomes, prognostic markers and endpoints. Furthermore, pb-CFR was indeterminant in 21% of cases post-PCI. Thus, it seems that in the search for a tool that can provide accurate data regarding microvascular function, IMR remains the current gold standard.

 

Can avoiding IVUS in complex PCI be justified?

Effect of Intravascular Ultrasound–Guided Drug-Eluting Stent Implantation. 5-Year Follow-Up of the IVUS-XPL Randomized Trial.

JACC Cardiovasc Interv 2020; 13:62-71
The advantages of IVUS-guided PCI in reducing cardiac death and repeat revascularization have been confirmed in a multitude of studies. The IVUS-XPL (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions) investigators report on the 5 years clinical results of their study in which 1400 patients with long coronary lesions (implanted stent length ≥28mm) were randomised to either IVUS-guided (n=700) or angiography guided (n=700) PCI with an everolimus-eluting stent. The primary outcome was the composite of MACE defined as cardiac death, target lesion-related MI, or ischemia driven TLR. At 5 years follow-up, IVUS-guided PCI was associated with a lower MACE rate (5.6% vs. 10.7%; HR: 0.50; 95% CI: 0.34-0.75; p=0.001). The difference was driven by a lower rate of TLR (4.8% vs. 8.4%; HR: 0.54; 95% CI: 0.33-0.89; p=0.007). By landmark analysis, MACE events between 1 and 5 years was lower in the IVUS-guided PCI group (2.8% vs. 5.2%; HR: 0.53; 95% CI: 0.29-0.95; p=0.03). Of note, the study was originally designed for 2 years follow-up and not 5 years and the optimal IVUS-guided attainment of an expansion index >1.0 is fairly aggressive by most comparisons.

 

CATHETER BASED VALVULAR INTERVENTION

 

Rivaroxaban not appropriate for routine use in patients undergoing TAVI

A Controlled trial of rivaroxaban after transcatheter aortic valve replacement.

NEJM 2020; 382:12-29
Early leaflet thrombosis of TAVI valves has been identified in more than 15% of patients and could be a treatable contributor to future adverse events. Whether routine anticoagulation could prevent leaflet thrombosis and ultimately improve clinical outcomes was the focus of the GALILEO trial. The trial randomized 1644 patients without an established indication for oral anticoagulation following TAVI to either rivaroxaban 10mg daily plus aspirin 75-100mg daily for the first 3 months or aspirin 75-100mg daily plus clopidogrel 75mg daily for the first 3 months. The primary efficacy outcome was the composite of death or thromboembolic events. The primary safety outcome was major, disabling, or life-threatening bleeding. The trial was terminated early due to safety concerns.
After a median of 17 months, death or a first thromboembolic event was greater in the rivaroxaban group (incidence rates 9.8 and 7.2 per 100 person-years respectively; HR:1.35; 95% CI: 1.01-1.81; p=0.04). Bleeding was more common in the rivaroxaban group (4.3 and 2.8 per 100 person-years; HR: 1.50; 95% CI: 0.95-2.37; p=0.08) as was death (5.8 and 3.4 per 100 person-years; HR: 1.69; 95% CI: 1.13-2.53). Of note, most of the deaths in the rivaroxaban group were sudden or were due to non- cardiovascular causes, and a minority of the patients who had died had died of a bleeding event. In addition, 37% of the patients discontinued rivaroxaban during the trial, and most deaths occurred long after drug discontinuation.

 

Novel intervention for tricuspid regurgitation

Transcatheter edge-to-edge repair for reduction of tricuspid regurgitation: 6-month outcomes of the TRILUMINATE single-arm study

Lancet 2019; 394:2002-2011
There is a paucity of definitive interventions for severe symptomatic secondary or functional tricuspid regurgitation (TR). Treatment is usually conservative despite an association with adverse outcomes independent of concomitant cardiac or valvular pathology. Only expert-level consensus is available to guide the timing of surgical tricuspid valve repair, which in the main is usually performed in combination with left-sided heart surgery. This has paved the way for the development of transcatheter-based intervention for TR. Given that tricuspid leaflet malcoaptation is the predominant defect in TR, an edge-to-edge clip technique, successfully adopted for treating mitral regurgitation (MitraClip), represents the most promising opportunity to effectively manage functional TR.
The TRILUMINATE study is a prospective multicenter single-arm study aimed at evaluating the safety and effectiveness of the TriClip transcatheter tricuspid valve repair system. Patients were eligible for the study if they had ≥moderate TR, ≥NYHA Class II, and had been adequately treated with optimal medical therapy but were regarded as high risk for surgery. Patients were excluded if they had a pulmonary artery systolic pressure >60 mmHg, prior tricuspid valve intervention or a pacemaker lead implanted in the right ventricle. The primary efficacy endpoint was a reduction in TR by at least one echocardiographic grade by 30 days and the primary safety endpoint was a composite of major adverse events at 6 months. The trial has completed recruiting and the follow-up is ongoing. This paper presented the first 6- month outcomes. From August 2017 to November 2018, 85 patients successfully received TriClip implantation. There was a 100% successful implantation rate. Of those, 71 patients (86%) had achieved a reduction in severity by at least 1 grade at 30 days (p<0.0001). At 6 months, only 3 (4%) of 84 patients had a documented major adverse event. There were, however, no device embolization, MI, or strokes. One patient withdrew prior to 6-month follow-up. Overall, TriClip appears to be a safe and feasible percutaneous method of managing significant functional TR, the caveat being this was not a randomized trial and therefore cannot be definitive regarding any medium- to long-term reduction in morbidity or mortality, for instance in comparison with conservative therapy or surgical intervention.

 

MISCELLANEOUS

 

Troponin rise post PCI confers an adverse prognosis

Peri-procedural elevated myocardial biomarkers predict adverse clinical outcomes following elective percutaneous coronary intervention: a comprehensive dose-response meta-analysis of 24 prospective studies with 44972 patients

Eurointervention 2019 DOI: 10.4244/EIJ-D-19-00737
How many of us request a troponin after PCI? Perhaps we would rather not know. Do we send the patient home, regardless? Do we look at the results or collect the data systematically? In the acute patient, is it just a marker of the underlying condition? In these days of ‘duty of candour’, do we discuss the possible implications of a large troponin rise (‘procedure related’, a ‘troponin blip’) with the patient? Is it meaningful to include peri-procedural markers in composite trial endpoints? This is a particularly important point when dissecting out the results of landmark trials. The authors performed a meta-analysis to evaluate the dose-response relationship between biomarker elevation and the risk of all-cause mortality and MACE following elective PCI. Many of us are not fans of meta-analyses, which have problems associated with publication bias, accessing patient-level data, mixed outcome measures, and variable follow-up periods, to name but four. But the authors worked according to the best standards, known as the MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines, and searched for studies between 1979 and 2018. Inevitably, the endpoints shifted from CK-MB to troponin in that study period and, rather than reporting a continuous variable, most studies reported the number in each group (1-3, 3-5, and >5 fold above the upper limit of normal, for example). And there was a lot of data manipulation to express results in a common format. With all those caveats, what they found was a post-procedural troponin >3-fold the 99th centile, and CK-MB > the 99th centile, were associated with increased mortality and MACE. For example, the OR for death if the troponin was 3-5 ULN was 1.5. Of course, it is impossible to correct for every variable, and it is highly likely that the higher marker elevations are found in patients with more extensive, complex or severe disease, and this may well be in the more co-morbid or frail, whose mortality is inevitably going to be higher than the others. Nevertheless, this study serves as a reminder that, on balance, a significant troponin rise at the time of elective PCI is not good for you, and it makes sense to minimise it whenever possible. This may, for instance, have implications for the extent of disease treated, the striving for ‘perfection’, or the drive to complete revascularisation. PCI is a trade-off. One has to know when to stop.

BCIS R&D Group Literature Update

January 2018

Michael Mahmoudi

Vijay Kunadian

Nick Curzen

PCI IN PRACTICE

MOST CONTROVERSIAL….Is PCI beneficial in stable single vessel disease?

Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial

R Al-Lamee et al.

The Lancet 2018; 391:31-40

In patients with stable angina, PCI has been associated with a reduction in the relief of angina but no placebo-controlled trials have been undertaken in this patient population. The ORBITA trial was a multicentre, randomised study of 230 patients designed to assess the effects of PCI versus placebo on exercise time. Key inclusion criteria were patients aged 18-85 years with angina, at least one angiographically significant lesion (≥70% on visual assessment). After enrolment, the study consisted of two consecutive phases: first 6-weeks consisting of optimizing anti-anginal therapy and the second 6 weeks during which patients underwent follow-up assessment including Canadian Cardiovascular Society angina severity, cardiopulmonary exercise testing, dobutamine stress echocardiography, blood pressure and heart rate monitoring. At enrolment, patients completed SAW and EQ-5D-5L questionnaire. In all patients, a research invasive FFR and iFR was also undertaken in the PCI group. Of note, the values of the FFR and iFR were not available to the operator making the PCI arm an angiography guided procedure & were negative in some cases.

The primary end point of the study was the difference in exercise time increment between the groups. Secondary end points included peak VO₂, change in exercise time to 1 mm ST segment depression, angina severity, physical limitation, angina stability and angina frequency. ORBITA demonstrated no significant difference in exercise time increment between the two groups (PCI minus placebo=16.6 seconds; 95% CI:-8.9-42; p=0.2). Similarly, there were no differences between the PCI arm and the placebo arm in any components of the secondary end point.  Interestingly, the exercise time did increase significantly in the PCI arm and not in the medical arm, but this was not the prespecified endpoint.

The conclusion was that “in patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure”.

The debate rages about the trial design but employing a sham arm makes this a powerful study.

Crush better than you thought in LM PCI?

Double Kissing Crush Versus Provisional Stenting for Left Main Distal Bifurcation Lesions

DKCRUSH-V Randomized Trial

S Chen, et al.

J Am Coll Cardiol 2017; 70:2605-17

There are varying PCI techniques for unprotected distal left main (ULM) disease including single stent strategy, provisional T-stenting (PS), crush technique, or culotte. No trial had previously compared DK crush with PS in the context of ULM disease. The DKCRUSH-V randomized trial was a prospective, randomised, international, multicentre study of 482 patients with distal ULM disease scheduled to undergo PCI to evaluate the comparative outcomes of DK crush with PS. The main inclusion criteria were silent ischemia, stable or unstable angina, MI>24 hours before treatment, distal left lesion (Medina 1,1,1 or 0,1,1) with >50% stenosis of both the ostial Cx and LAD by visual assessment.

The primary end point was target lesion failure defined as the composite of cardiac death, target vessel MI, or clinically driven target lesion revascularization at 1 year follow-up. Secondary end point included all cause death, all MI, periprocedural troponin I release, clinically driven revascularization, angina, and in-stent restenosis. In this study, DK crush was associated with a significantly lower primary end point (5% vs. 10.7%; p=0.02). DK crush was also associated with lower rates of target vessel MI (0.4% vs. 2.9%; p=0.03). Clinically driven target vessel revascularization (3.8% vs. 7.9%; p=0.06) and angiographic restenosis (7.1% vs. 14.6%; p=0.1) were numerically lower with DK crush.

In this randomised trial, DK CRUSH was associated with a superior outcome compared to PS in LM PCI.

Why do scaffolds thrombose?

Mechanisms of Very Late Bioresorbable Scaffold Thrombosis

K Yamaji, et al.

J Am Coll Cardiol 2017; 70:2330-44)

Fully bioresorbable coronary scaffolds have the theoretical advantages of reducing the long term risk of device related adverse events such as restenosis and thrombosis as well as avoiding permanent caging of the coronary artery. However, despite the initial favourable results associated with the Absorb bioresorbable vascular scaffold (BVS), a number of studies have indicated that the BVS is associated with greater risks of target vessel myocardial infarction and device thrombosis as compared to second generation drug-eluting stents. The INVEST registry, an independent international consortium of investigators, has been set up to investigate the underlying mechanism(s) of very late BVS thrombosis as assessed by OCT.

Over a period of 4 years, 36 patients with 38 lesions with very late BVS thrombosis underwent OCT. The underlying mechanisms of very late thrombosis were as follows: scaffold discontinuity (42.1%), malapposition (18.4%), neoatherosclerosis (18.4%), underexpansion or scaffold recoil (10.5%), uncovered struts (5.3%), and edge related disease progression (2.6%).

Future randomized studies will be required to determine whether novel scaffold designs and optimized implantation techniques can reduce the risk of very late scaffold thrombosis.

Embolic Protection in SVG Intervention-Not worthwhile after all?

Outcomes of Saphenous Vein Graft Intervention With and Without Embolic Protection Device. A Comprehensive Meta-Analysis

T Paul et al.

Circ Cardiovasc Interv 2017; 10:e005538

Despite a class I recommendation for the use of embolic protection devices (EPD) for saphenous vein graft (SVG) intervention, the results of clinical studies have produced conflicting results with regards to this recommendation. Paul et al have undertaken a meta-analysis of 8 studies including 52,893 patients (EPD used in 11,506 patients and EPD not used in 41,387 patients) to compare all-cause mortality, major adverse cardiovascular events (MACE), MI, or target vessel revascularization in patients undergoing SVG PCI with or without EPD.

In this meta-analysis, there were no significant differences in all cause mortality (OR,0.79; CI:0.55-1.12; p=0.19), MACE (OR,0.73; CI:0.51-1.05; p=0.09), late MI (OR,0.80; CI:0.52-1.23; p=0.3), or target vessel revascularization (OR,1.0; CI:0.95-1.05)p=0.94) between the two groups. The lack of differences may be related to potent pharmacotherapy including the use of vasodilator agents to manage no reflow, the use of dual antiplatelet therapy, improved procedural techniques, as well as the availability of less bulky devices.

Based upon these data, the authors have recommended a revision of current recommendations with regard to routine use of embolic protection.

ACUTE CORONARY SYNDROMES

A very old myth debunked!

CULPRIT-SHOCK

H Thiele, et al.

New England J Med 2017; 377:2419-32)

The optimal revascularization strategy in patients presenting with STEMI, multivessel coronary artery disease (CAD), and cardiogenic shock is uncertain. The CULPRIT-SHOCK investigators randomized 706 patients with acute MI (AMI), multivessel CAD and cardiogenic shock to either PCI of the culprit lesion with the option of staged revascularization of non-culprit lesions or immediate multi-vessel PCI including efforts to recanalize chronic total occlusions. Multi-vessel CAD was defined as disease in at least two major vessels ≥2 mm in diameter with >70% stenosis and an identifiable culprit lesion. Cardiogenic shock was defined as systolic blood pressure <90mmHg for longer than 30 minutes or the use of catecholamine therapy to maintain the systolic blood pressure of at least 90mmHG, clinical signs of pulmonary congestion, and signs of impaired organ perfusion with at least one of the following features: altered mental status, cold and clammy skin and limb, oliguria with urine output <30ml/hour or arterial lactate >2nmol/L.

The primary end point of the trial was a composite of death or severe renal failure leading to renal-replacement therapy within 30 days of randomization. Safety end point were bleeding and stroke. At 30 days, the primary end point was significantly lower in patients randomised to culprit lesion PCI (45.9% vs. 55.4%; RR:0.83; 95% CI:0.72-0.98; p=0.01). The relative risk of death in the culprit lesion only PCI was 0.84 (95% CI:0.72-0.98; p=0.03) and the relative risk of renal-replacement therapy was 0.84 (95% CI:0.49-1.03; p=0.07). The risk of bleeding (16.6% vs. 22%; p=0.07) and stroke (3.5% vs. 2.9%; p=0.68) were similar in the two groups.

In this group of patients with cardiogenic shock, culprit lesion PCI is superior to multivessel PCI, a difference that is driven by a lower mortality.

Early switch back to good old clopidogrel?

Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study

Thomas Cuisset et al

European Heart Journal, Volume 38, Issue 41, 1 November 2017, Pages 3070–3078

The TOPIC trial evaluated the benefit of switching dual antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1 month after ACS. 645 patients admitted with ACS requiring intervention, on aspirin and a newer P2Y12 blocker and without adverse event at 1 month, were assigned to switch to aspirin and clopidogrel (switched DAPT) or continuation of their drug regimen (unchanged DAPT). The primary outcome was a composite of cardiovascular death, urgent revascularization, stroke and bleeding as defined by the Bleeding Academic Research Consortium (BARC) classification ≥2 at 1 year post ACS. Of the total 645 patients, 322 patients were in the switched DAPT and 323 were in the unchanged DAPT group. The primary endpoint occurred in 13.4% in the switched DAPT group and in 26.3% in the unchanged DAPT (P < 0.01) driven by BARC ≥ 2 bleeding that occurred in 4.0% in the switched DAPT and 14.9% in the unchanged DAPT group (P < 0.01).

The investigators concluded that a switched DAPT is superior to an unchanged DAPT strategy to prevent bleeding complications without increase in ischaemic events following ACS.

An argument for earlier angiography? Roll on RAPID NSTEMI!

Impact of total occlusion of culprit artery in acute non-ST elevation myocardial infarction: a systematic review and meta-analysis 

Abdur R. Khan et al

European Heart Journal, Volume 38, Issue 41, 1 November 2017, Pages 3082–3089

This was a meta-analysis to estimate the difference in outcomes between totally occluded and non-occluded culprit arteries in patients with NSTEMI. 40 777 patients from 7 studies were included. The outcomes assessed were clinical presentation (Killip class), left ventricular ejection fraction, time to angiography, major cardiac adverse events (MACE) and all-cause mortality. 25.5% patients had an occluded culprit artery (40% right coronary and 33% left circumflex artery). There was an increased risk of both MACE (short-term, P = 0.0003; medium- to long-term, P = 0.001) and all-cause mortality (short-term P < 0.0001; medium to long-term P = 0.01) with total occlusion of the culprit artery.

This meta-analysis suggests that patients with NSTEMI who have a totally occluded culprit vessel on coronary angiography are at higher risk of mortality and major adverse cardiac events.

MULTIVESSEL REVASCULARISATION

Is PCI getting better?

Clinical outcomes of state-of-the-art percutaneous coronary revascularization in patients with de novo three vessel disease: 1-year results of the SYNTAX II study

Javier Escaned et al

European Heart Journal, Volume 38, Issue 42, 7 November 2017, Pages 3124–3134

The SYNTAX II investigators sought to evaluate if recent technical and procedural developments in percutaneous coronary intervention (PCI) influence clinical outcomes in patients with three-vessel (3VD) coronary artery disease in this multicentre study conducted in 22 centres from 4 European countries. The SYNTAX-II strategy included: heart team decision-making utilizing the SYNTAX Score II, coronary physiology-guided revascularisation, implantation of thin strut bioresorbable-polymer drug-eluting stents, intravascular ultrasound (IVUS)-guided stent implantation, contemporary chronic total occlusion revascularisation techniques and guideline-directed medical therapy. MACCE consisted of composite of all cause death, cerebrovascular event, any myocardial infarction and any revascularisation at one year was compared to a predefined PCI cohort and the historical CABG cohort of the original SYNTAX-I trial. 454 patients of 708 screened underwent PCI. At one year, the SYNTAX-II strategy was superior to the equipoise-derived SYNTAX-I PCI cohort (MACCE SYNTAX-II 10.6% vs. SYNTAX-I 17.4%; P = 0.006). This difference was driven by a significant reduction in the incidence of MI (P = 0.007) and revascularisation (P = 0.015). Rates of all-cause death and stroke (P = 0.71) were similar. The rate of definite stent thrombosis was significantly lower in SYNTAX-II (P = 0.045).

Thus, the clinical outcomes with the SYNTAX-II strategy were associated with better clinical results compared to the PCI performed in the original SYNTAX-I trial.

OLDER PATIENTS

Good news for DES in the elderly

DES or BMS for SENIORS

O Varenne, et al.

The Lancet 2018; 391:41-50

The optimal PCI strategy for elderly patients remains ill defined as many such patients have been excluded from landmark PCI studies purely based upon their age criteria. The prevalence of elderly patients are increasing, they often have complex coronary artery disease, and are at increased risk of bleeding from dual antiplatelet therapy. The SENIOR trial is a randomised, single blind, multicentre study of 1200 patients aged ≥75 years presenting with stable angina, silent ischemia, or an acute coronary syndrome including STEMI, and whom had at least one coronary stenosis of at least 70% severity (≥ for the left main) deemed eligible for PCI that were randomised to PCI with either the bioabsorbable polymer DES (SYNERGY, Boston Scientific)) or a BMS (Omega or Rebel; Boston Scientific). Of note, the duration of dual antiplatelet therapy was 1 month in stable or silent cases and 6 months in unstable cases in both groups.

The primary end point was the cumulative incidence of major adverse cardiac and cerebrovascular events (MACCE) defined as a composite of all-cause mortality, MI, ischaemic driven target lesion revascularization, or stroke at 1 year. Key secondary end points included bleeding complications, and definite or probable stent thrombosis. In this study, the rate of MACCE was significantly lower in the DES group (12% vs. 16%; RR:0.71; 95% CI:0.52-0.94; p=0.02). Bleeding complications (5% vs. 5%; p=0.68), and stent thrombosis (1% vs. 1%; p=0.13) were similar in both groups.

The SENIOR trial indicates that in patients aged ≥75 years undergoing PCI, a strategy of PCI with the SYNERGY stent and short duration of dual antiplatelet therapy is safe and efficacious as compared to a BMS.

Counter-ageism?

Revascularisation compared with initial medical therapy for non-ST-elevation acute coronary syndromes in the elderly: a meta-analysis

Sonali R Gnanenthiran et al

Heart 2017; 103 1932-1933

This meta-analysis compared routine invasive therapy with initial medical management in the older patients (≥75 years) presenting with NSTEACS. Endpoints included long-term mortality, myocardial infarction (MI), revascularisation, rehospitalisation, stroke and major bleeding reported as ORs. 4 randomised trials and 3 observational studies met inclusion criteria, enrolling a total of 20 540 patients followed up from 6 months to 5 years. Analyses restricted to randomised controlled trials (RCTs) confirmed a reduction in myocardial infarction (Odds Ratio 0.51, Confidence Interval 0.40-0.66), revascularisation (OR 0.27, CI 0.13-0.56) and a trend to reduced mortality (OR 0.84, CI 0.66-1.06) at the expense of major bleeding (OR 2.19, CI 1.12-4.28) in the invasive group compared to the conservative group.

The authors concluded that routine invasive therapy reduces myocardial infarction and repeat revascularisation and may reduce mortality at the expense of major bleeding in older patients with NSTEACS.

VALVULAR HEART DISEASE

Not what we expected?

Emergency treatment of decompensated aortic stenosisDario Bongiovanni et al

Heart 2018;104:23–29

Bongiovanni and colleagues assessed the early outcome of emergency transcatheter aortic valve implantation (eTAVI) versus emergency balloon aortic valvuloplasty (eBAV) followed by TAVI under elective circumstances. The authors defined emergency conditions as: cardiogenic shock with requirement of catecholamine therapy, severe acute dyspnoea (NYHA IV), cardiac resuscitation or mechanic respiratory support. In 5 German centres, 23 patients (logistic Euroscore 37.7%±18.1) underwent eTAVI and 118 patients underwent eBAV (logistic Euroscore 35.3%±20.8). In the eTAVI group, immediate procedural mortality was 8.7%, compared with 20.3% for the eBAV group (p=0.19). After 30 days, cardiovascular mortality for the eTAVI group was 23.8% and for the eBAV group 33.0% (p=0.40). Of note, the elective TAVI performed after eBAV (n=32, logistic Euroscore 25.9%±13.9) displayed an immediate procedural mortality of 9.4% and a cardiovascular mortality after 30 days of 15.6%. Major vascular complications were significantly more likely to occur after eTAVI (p=0.01) as well as stroke (p=0.01).

In this multicentre cohort, the immediate procedural and 30-day mortality of eTAVI and eBAV were high, and mortality of secondary TAVI subsequent to eBAV was higher than expected.

Conscious Sedation for TAVR definitely a good thing

Conscious Sedation Versus General Anesthesia for Transcatheter Aortic Valve Replacement. Insights from the National Cardiovascular Data Registry Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.

M Hyman, et al.

Circulation 2017; 136:2132-2140

Despite the increasing use of conscious sedation in patients undergoing TAVR, the evidence base for this practice is limited. Hyman et al examined the National Cardiovascular Data Registry Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry between April 2014-June 2015 to characterize the choice of anaesthesia (conscious sedation versus general anaesthesia) in patients undergoing elective TAVR and compare in-hospital mortality, 30-day mortality, in-hospital and 30-day death/stroke, procedural success, ITU and hospital length of stay, and rates of discharge to home.

In this registry, conscious sedation was used in 15.8% of cases. Conscious sedation was associated with significantly lower rates of in hospital mortality (1.6% vs. 2.5%; p=0.03), 30 day mortality (2.9% vs. 4.1%; p=0.03), ITU and hospital length of stay (6 days vs. 6.5 days; p<0.001), combined 30 day death/stroke (4.8% vs. 6.4%; p<0.001). The rates of vascular complications, bleeding, and pacemaker implantation were similar in the two groups.

These results indicate that conscious sedation is safe and may be associated with potential cost savings.

Most surprising result this month?

Mechanical aortic valve replacement in non-elderly adults: meta-analysis and microsimulation

Nelleke M Korteland et al

European Heart Journal, Volume 38, Issue 45, 1 December 2017, Pages 3370–3377

Korteland et al sought to provide a detailed overview of outcome after contemporary mechanical aortic valve replacement (AVR) in young patients. They undertook a systematic review of studies (29 publications, 5728 patients with 32 515 patient-years of follow-up = pooled mean follow-up: 5.7 years) reporting clinical outcome after AVR with bileaflet mechanical valves with a mean patient age ≥18 and ≤55 years. Mean age at surgery was 48 years. Early mortality risk was 3.15%, late mortality rate was 1.55%/year with 38.7% of late deaths were related to valve. Thromboembolism rate was 0.90%/year, major bleeding 0.85%/year, non-structural valve dysfunction 0.39%/year, endocarditis 0.41%/year, valve thrombosis 0.14%/year and reintervention 0.51%/year, mostly due to non-structural valve dysfunction and endocarditis. This translated to an estimated life expectancy of 19 years for a 45-year-old compared with the general population of 34 years and lifetime risks of thromboembolism, bleeding and reintervention of 18%, 15%, and 10%, respectively.

The outcome after mechanical AVR in young adults is characterized by suboptimal survival and considerable lifetime risk of anticoagulation-related complications, and also reoperation.

Intuitive but still useful?

Staging classification of aortic stenosis based on the extent of cardiac damage

Philippe Généreux et al

European Heart Journal, Volume 38, Issue 45, 1 December 2017, Pages 3351–3358

This study evaluated the prognostic impact of a newly defined staging classification characterising the extent of extra-aortic valve cardiac damage among patients with severe aortic stenosis (AS) undergoing aortic valve replacement (AVR). The investigators pooled data from 1661 patients with severe AS from the PARTNER 2 trials and classified them according to the presence or absence of cardiac damage as detected by echocardiography prior to AVR: Stage 0- No extravalvular cardiac damage (2.8%); Stage 1- Left ventricular damage (12.8%); Stage 2- Left atrial or mitral valve damage (50.8%); Stage 3- Pulmonary vasculature or tricuspid valve damage (24.9%) and Stage 4- Right ventricular damage (8.7%). One-year mortality was 4.4% in Stage 0, 9.2% in Stage 1, 14.4% in Stage 2, 21.3% in Stage 3, and 24.5% in Stage 4 (P_trend < 0.0001). The extent of cardiac damage was independently associated with increased mortality after AVR (P < 0.0001).

The authors concluded that this new staging classification objectively characterises the extent of cardiac damage associated with AS and has important prognostic implications for clinical outcomes after aortic valve replacement.

IMAGING

An angiogram-derived  alternative to FFR for physiology?  The start of an avalanche of similar systems

Diagnostic Accuracy of Angiography-Based Quantitative Flow Ratio Measurements for Online Assessment of Coronary Stenosis.

B Xu, et al.

J Am Coll Cardiol 2017; 70:3077-87

Despite the wealth of evidence in support of FFR–guided management strategy, the adoption of FFR remains at best modest in part due to cost, concerns regarding the adverse effects of adenosine, and wire related complications. Quantitative flow ratio (QFR) has emerged as a novel method for evaluation of FFR based upon 3-dimensional angiographic reconstruction and fluid dynamics algorithms. The FAVOR II China study is a prospective, multicentre trial of 308 consecutive patients who had at least 1 lesion with a stenosis of 30-90% severity and a reference diameter ≥2mm based on visual assessment and measured QFR, quantitative coronary angiography (QCA), and wire based FFR (RadiAnalyzer Xpress instrument and Certus pressure wire with adenosine-5-triphosphate as the vasodilator) were assessed online in a blinded fashion during coronary angiography and reanalysed offline at an independent core laboratory.

The primary end point of the study was that QFR would improve the diagnostic accuracy of coronary angiography. Patient and vessel-level diagnostic accuracy of QFR was 92.4% (95% CI:88.9%-95.1%) and 92.7% (95% CI:89.3%-95.3%), both of which were above the pre-specified target value of 75% (p<0.001). Sensitivity and specificity in identifying hemodynamically significant stenosis defined as FFR ≤0.8 were significantly higher for QFR than QCA (sensitivity:94.6% vs. 62.5%; P<0.001); specificity 91.7% vs. 58.1%; p<0.001). Positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio for QFR were 85.5%, 97.1%, 11.4 and 0.06 respectively.

The study has concluded that QFR is a feasible and accurate method for identifying significant coronary stenosis during coronary angiography.

What can we do about this?

Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an individual patient data pooled analysis from seven randomized trials

Suzanne de Waha et al

European Heart Journal, Volume 38, Issue 47, 14 December 2017, Pages 3502–3510

This study evaluated the relationship between microvascular obstruction (MVO) and all cause mortality, hospitalization for heart failure, and reinfarction following primary percutaneous coronary intervention (PPCI) in STEMI. 1688 patients from 7 randomized PPCI trials in which MVO was assessed using late gadolinium enhancement cardiac MRI (CMR) within 7 days after reperfusion were evaluated. Median time to CMR after STEMI was 3 days, and median duration of clinical follow-up was 365 days. MVO was present in 56.9% of patients. The authors demonstrated that the extent of MVO (per 1.0% absolute increase) was associated with subsequent mortality and hospitalization for heart failure (P<0.0001). MVO remained significantly associated with all-cause mortality even after further adjustment for infarct size (P = 0.03) but not significantly related to subsequent reinfarction (P = 0.29).

The presence and extent of MVO measured by CMR after PPCI in STEMI were strongly associated with mortality and hospitalization for heart failure within 1 year.

New imaging or any imaging?

Optical frequency domain imaging vs. intravascular ultrasound in percutaneous coronary intervention (OPINION trial): one-year angiographic and clinical results

Takashi Kubo et al

European Heart Journal, Volume 38, Issue 42, 7 November 2017, Pages 3139–3147

This was a multicentre, randomised study designed to test the non-inferiority of Optical frequency domain imaging (OFDI)-guided PCI compared with Intravascular ultrasound (IVUS) -guided PCI in terms of clinical outcomes. The primary endpoint was target vessel failure defined as a composite of cardiac death, target-vessel related myocardial infarction, and ischaemia-driven target vessel revascularization until 12 months after the PCI. 829 patients were randomly allocated to receive OFDI-guided PCI (n = 414) or IVUS-guided PCI (n = 415). Target vessel failure occurred in 5.2% patients undergoing OFDI-guided PCI, and 4.9% patients undergoing IVUS-guided PCI, demonstrating non-inferiority of OFDI-guided PCI to IVUS-guided PCI (P_{non-inferiority} = 0.042).

In this study the 12-month clinical outcome in patients undergoing OFDI-guided PCI was non-inferior to that of patients undergoing IVUS-guided PCI.