What are the questions to be answered by future studies in CTOs? Ulf Landmesser, Berlin, Germany

1. Univ. Prof. Dr. med. Ulf Landmesser
Chairman, Department of Cardiology
Chair, Center for Cardiovascular Medicine
Charité Universitätsmedizin Berlin
Germany
WHAT ARE THE
QUESTIONS TO BE
ANSWERED BY FUTURE
STUDIES IN CTOs ?

2. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Clinical impact of CTO recanalisation -
in particular on prognosis ?
01
Further optimization of CTO interventions ?
02
What are the questions to be answered by
future studies in CTOs ?

3. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
When CTO-PCI should be done ?
Bilakis ES, Mashayekhi K, Burke MN. Circulation. 2019; 139(14):1684-1687

4. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Recent randomized clinical CTO trials
DECISION-CTO EURO-CTO
Design Open label RCT Open label RCT
Setting Korea
19 centers
Europe
26 centers
Subjects SAP or ACS [74% vs 26%] SAP
Recruitment (N)
Target (N)
Time (Yrs)
815
1284
6
407*
600/1200
3
Comparison OMT vs CTO-PCI OMT vs CTO-PCI
Primary Endpoint MACCE 3yr
[Death, MI, stroke, repeat
revascularisation]
SAQ health status 12M
Death, MI 3yr
Werner GS et al.;
Eur Heart J. 2018; 39(26):2484-2493
Lee SW et al.;
Circulation 2019;139(14):1674-1683.

5. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
EuroCTO trial – Clinical Outcomes
Werner GS et al.; Eur Heart J. 2018 Jul 7;39(26):2484-2493

6. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
ISCHEMIA-CTO Trial: Aim and Hypotheses
Evaluation of outcome and symptoms following CTO-PCI vs. OMT in patients
with significant myocardial ischemia
• In asymptomatic patients with ≥ 10% of myocardial ischemia: PCI is
superior to OMT for MACCE outcomes (30 % reduction in primary composite
endpoint)
• In symptomatic patients with ≥ 5% of myocardial ischemia: PCI is
superior to OMT for life quality measured (Mean difference in quality of life
score of 8 points after 6 months in the PCI vs. OMT arm).
Courtasy of Evald Hoej Christiansen, Aarhus University Hospital

7. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Inclusion criteria
• CTO in native coronary artery
• Target artery ≥ 2.5 mm
Cohort A – Asymptomatic patients
• Myocardial ischemia (≥ 10% of LV) in a
territory supplied by CTO assessed by
stress test
Cohort B - Symptomatic patients
• Myocardial ischemia (5% of LV) in a
territory supplied by CTO as assessed by
stress test
• CCS > 2 and/or SAQ QoL score ≤ 60 after
treating non CTO lesions and after OMT
Exclusion criteria
• NSTEMI or STEMI within 1 month
• Coronary anatomy not suitable for CTO-
procedure
• Life expectancy < 2 years
• Severe chronic pulmonary disease (FEV1 <
30 % of predicted value)
• Contraindication to dual anti-platelet
therapy
• Pregnancy
• eGFR < 30 mL/min
• In multi-vessel disease: if it is deemed
unsafe to treat the non-CTO lesion first.
Courtasy of Evald Hoej Christiansen, Aarhus University Hospital
ISCHEMIA-CTO Trial: Eligibility criteria

8. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Cohort A - Primary Endpoint (FU 5 years)
• Composite endpoint of MACCE (all-cause mortality, stroke,
myocardial infarction, clinically driven revascularization*), hospitalization for heart
failure or incidence of malignant arrhythmias.
*CCS class ≥ II and/or QoL score < 60. Same criteria used as for allocation to
Cohort B
Cohort B – Primary Endpoint (after 6 months)
• SAQ Quality of Life Assessment after 6 months.
ISCHEMIA-CTO Trial: Primary endpoints
Courtasy of Evald Hoej Christiansen, Aarhus University Hospital

9. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
ISCHEMIA-CTO Trial -
Participating sites:
(Nordic and Spanish)
United Kingdom
Belfast Health and Social Care Trust Dept. Cardiology,
S. Walsh
Department of Cardiology, St George's University
Hospitals NHS Foundation Trust, London, J. Spratt
Barts Health Trust, London, E. Smith
University Hospital of Bristol, J. Strange
Netherlands
VU University Medical Center, Amsterdam, Paul
Knappen
(Invited)
Spain
Hosptial Clinico San Carlos, Madrid, J. Escaned
Hospital Clinic, Barcelona, A. Regueiro
Hospital del Mar, Barcelona, B. Vaquerizo
Hospital de Bellvitge, Barcelona, L. Teruel
Hospital Universitari de Tarragona Joan XXIII, M.
Mohandes
*
* ****
*
*
*
*
**
*
*
*
* *
*
Denmark
Skejby, E. Christiansen
Rigshospitalet, HH. Tilsted
Gentofte, NT. Nielsen
Odense, K. Veien
Roskilde, H. Kelbæk
Sweden
Sahlgrenska University Hospital, D. Ioanes
Skaane University Hospital, G. Olivecrona
Stockholm South Central Hospital, U. Jensen
Gävle Hospital, R. Kastberg
Finland
Heart Hospital, Tampere University Hospital, O. A.
Kajander
Turku University Hospital, M. Pietilä
Helsinki University Central Hospital, Pasi Karjalainen
Lahti Central Hospital, Tomi Kaukonen
Kuopio University Hospital, Hannu Romppanen
Joensuu Central Hospital, Tuomas Rissanen
Norway
Bergen University Hospital, Anja Øksnes
Estonia
North-Estonia Medical Centre, Tallinn, Peep Laanmets
*
*
*

10. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
ISCHEMIA Trial - Stable CAD with at least Moderate Ischemia

11. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
ISCHEMIA Trial - Stable CAD with at least Moderate Ischemia

12. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Ischemia – Randomized Clinical Trial
1
JAMA Cardiol. 2019 Mar 1;4(3):273-286.

13. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser1
JAMA Cardiol. 2019 Mar 1;4(3):273-286.
Ischemia – Randomized Clinical Trial

14. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser1

15. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Zimmermann FM et al.; Eur Heart J. 2019 Jan 7;40(2):180-186

16. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Zimmermann FM et al.; Eur Heart J. 2019 Jan 7;40(2):180-186

17. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Clinical impact of CTO recanalisation -
in particular on prognosis ?
01
Further optimization of CTO interventions ?
02
What are the questions to be answered by
future studies in CTOs ?

18. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Procedural optimization based on intravascular imaging
1
Neumann FJ et al.; Eur Heart J. 2019 Jan 7;40(2):87-165.

19. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Eur Heart J 2018 Sep 14;39(35):3281-3300

20. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Intravascular Lithotrypsy (IVL):
a new method to prepare calcified coronary lesions

21. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Summary of PCI optimization targets by IC Imaging
Eur Heart J 2018 Sep 14;39(35):3281-3300

22. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Coronary disease
High resolution intra-coronary imaging - Optical Coherance Tomography
• Engel L, Landmesser U.
JACC Cardiovasc Imaging 2019;12(2):297-306
• Leistner et al. & Landmesser U.
Catheter Cardiovasc Intervention 2019 (in press)
• Jaguszewski et al. & Landmesser U.
JACC Cardiovasc Interv. 2017; 10: 489-499
• Landmesser U.
Nat Rev Cardiol 2014
• Jaguszewski M et al. & Landmesser U.
J Am Coll Cardiol 2012

23. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
ILUMIEN IV: OPTIMAL PCI
2556-3568 pts with high-risk clinical or angiographic
features undergoing PCI at 125 centers in the US,
Canada, Western Europe, and Asia-Pacific
Follow-up: Minimum 1 year, maximum 2 years
Primary endpoints:
1) Minimal stent area (MSA) by OCT (powered for superiority)
2) Target vessel failure (event-driven, powered for superiority)
(Principal Investigators: Ziad Ali and Ulf Landmesser)
HR clinical:
Diabetes
HR angio:
Troponin+ ACS culprit
Stent length ≥28 mm
2-stent bifurcation
Severe calcification
CTO
Diffuse/MF ISR
*ESRD not excluded
Randomize 1:1
Final OCT (blinded in angiography arm)
OCT-guided*
PCI
Angiography-guided
PCI

24. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Clinical impact of CTO recanalisation -
in particular on prognosis ?
01
Further optimization of CTO interventions ?
02
What are the questions to be answered by
future studies in CTOs ?

25. HERZMEDIZIN DER ZUKUNFT
Ulf Landmesser
Clinical impact of CTO recanalisation -
in particular on prognosis ?
01
Further optimization of CTO interventions ?
02
What are the questions to be answered by
future studies in CTOs ?