Carlo Di Mario - Recent Publications & Research in CTO: 2015-16

Recent Publications &
Research in CTO: 2015-16
Carlo Di Mario, MD, FESC, FACC, FRCP
Carlotta Sorini Dini, MD
Univ. Florence & Careggi Hospital

Manuscripts Published on CTO
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2010 2011 2012 2013 2014 2015 2016

• Epidemiology
• Physiology
• Outcome Data
• Predictors
• Technique
• Imaging
• Stents in CTO
CTO Published Manuscripts 2015-2016 :
Rapid Review of the Recent CTO Literature

 CTO in 20.3% of angiographies in 4140 patients
 January-October 2014, single high volume centre (Quebec)
 Exclusion criteria: history of coronary artery bypass graft (CABG)
 Treatment: 9% PCI, 34% CABG, 57% medical therapy
NSTEMI
41%
Stable CAD
48%
STEMI
8%
Other
3%
Clinical presentation Viability testing
Viability
68%
No viability
6%No testing
26%
Azzalini et al In press Am J Cardiol 2016

Azzalini et al In press Am J Cardiol 2016
Indipendent predictors of PCI
Success PCI : 64.6%

ACCF/AHA/SCAI guidelines for PCI

European Heart Journal (2015)36, 3189–3198
 IRCTO is a prospective real world multicentre registry
a total of 1777 patients were enrolled for an overall CTO prevalence of 13.3%.
12 high-volume Italian centres
Strategies: MT(medical therapy) in 826 patients (46.5%), PCI in 776 patients
(43.7%), and CABG in the remaining 175 patients (9.8%)
 1-year follow-up: patients undergoing PCI showed:
A) lower rate of major adverse cardiac and cerebrovascular events (MACCE)
(2.6% vs. 8.2% and vs. 6.9%;P.0.001 and P.0.01) and cardiac death (1.4% vs. 4.7%
and vs. 6.3%; P.0.001 and P.0.001) in comparison with those treated with MT and
CABG, respectively.
B) after propensity score matching analysis, patients treated with PCI showed
lower incidence of cardiac death (1.5 vs. 4.4% P.0.001), acute myocardial
infarction (1.1 vs. 2.9% P 0.03), and re-hospitalization (2.3 vs. 4.4% P 0.04) in
comparison with those managed by MT

European Heart J: Sept 2015
Angiographic characteristics of CTO

Am J Cardiol. 2016 Apr 1;117(7):1031-8
2368 patients with coronary heart disease and diabetes mellitus enrolled in the BARI
2D trial
Revascularization + intensive medical therapy ( PR) vs intensive medical therapy
alone (IMT)
CTO prevalence 41 % (972 patients)
482 patients (41%) in PR group and 490 patients (41%) in IMT group
In the PR group, patients with CTO were more likely to be selected for the coronary
artery bypass grafting stratum (CABG 62% vs PCI 31%, p <0.001)

 Single centre COMMIT-HF registry
 January 2009-Dicember 2014
 Follow-up: 12 months
 consecutive nonselected patients hospitalized in cardiology wards and
intensive cardiac care units with a diagnosis of systolic HF
 278 patients (41.2%) with CTO
 The patients with CTO had a higher prevalence of previous MI (77% vs 66%)
and CABG (38% vs 26%)
Tajstra, Pyka et al J Am Coll Cardiol Intv 2016:9:1790-7

Tajstra, Pyka et al J Am Coll Cardiol Intv 2016:9:1790-7
PCI only in 4.4% patients
NO viability testing was performed

1212 patients with an EF of 35% or less and coronary artery disease amenable to CABG.
Randomized to CABG plus medical therapy (n=610 ) or medical therapy alone (n=602 )
Velazquez, Kerry et al
N Engl J Med 2016

European Heart Journal , Sept 2016

Stuijfzand ,Eur Heart J Cardiovasc Imaging 2016 Sep 1
Even in the presence of angiographically
well-developed collateral arteries, the
vast majority of CTO patients with a
preserved LVEF showed significantly
impaired perfusion
76 patients with CTO and preserved LVEF
PET to assess myocardial blood flow
(MBF) and coronary flow reserve
MBF of the target area during
hyperaemia was significantly lower when
compared with the remote area (1.37+0.37
vs. 2.63+0.71 mL /min/g, P 0.001)

• 14,441 patients with CTO (16%)
and 75,431 patients without CTO
• January 2005-January 2012
• CTO group vs non CTO group
• Follow-up mean: 3.1 years
Ramunddal, Hoebers et al J Am Coll Card Intv 2016;9: 1535-44
CTO indipendent predictor mortality

Ramunddal, Hoebers et al
J Am Coll Card Intv 2016;9: 1535-44

Ramunddal, Hoebers et al J Am Coll Card Intv 2016;9: 1535-44
Risk long-term mortality Successful revascularisation
Successful revascularisation 54.4%

Long-term impact of CTO successful recanalization on
mortality
LP. Hoebers et al IJC 2015

Thai, Catheter Cardiov Intv 85:781–794 (2015)

LONG-TERM FOLLOW UP (median FU 30-month)
Coronary CTO in the nonculprit artery in patients presenting with ST- segment
elevation myocardial infarction is associated with increased short- and long-term all-
cause mortality.

480 STEMI patients with a CTO in a non-infarct-related artery
Henriques , EuroIntervention 2016;12:423-430
Mortality in STEMI patients with a single CTO
stratified according to culprit-related artery
Mortality in STEMI patients with a single CTO
stratified according to CTO-related artery

http://www.exploretrial.com/background.html
José PS Henriques

http://www.exploretrial.com/background.html
Additional PCI of a CTO located
in the LAD may improve LVEF
and clinical outcome during
follow up.
Results

• Occlusion characteristics (stump/length/calcium/tortuosity)
J-CTO Score
Morino et al. JACC Cardiovasc Interv 2011

CL score- clinical and lesion related score
Alessandrino, JACC Interv 2015

Christopoulos,
JACC Interv 2016

Karatasakis, Internat J Cardiol 2016

Data from 4 centers involving 240 consecutive
CTO lesions with pre-procedural coronary
computed tomography angiography were
analyzed.
Successful guidewire (GW) crossing ≤30 min
was set as an endpoint to eliminate operator bias
JACC Cardiovasc Interv. 2015 Feb;8(2):257-67

JACC Cardiovasc Interv. 2015 Feb;8(2):257-67
Conclusion: the CT-RECTOR
score represents a simple and
accurate noninvasive tool for
predicting time-efficient GW
crossing that may aid in grading
CTO difficulty before PCI.

Suzuki, Cathet Cardiov Interv 2016
Crossing success: 77%
PCI success: 68%

Wilson WM, Walsh SJ, Yan AT, et al. Heart 2016;102:1486– 1493.
First attempt success rate by a hybrid-trained CTO operator was 79%.
The success rate during the subsequent procedure was 87%
1,211 patients, 7 hospital in UK
Hybrid approach improves success of chronic total
occlusion angioplasty

Hybrid approach improves success of chronic total
occlusion angioplasty
1,211 patients, 7 hospital in UK
Adverse eventsFinal strategy adopted
AWE= anterograde wire escalation
ADR= anterograde dissection re-entry
RWE= retrograde wire escalation
RDR= retrograde dissection re-entry
Wilson WM, Walsh SJ, Yan AT, et al. Heart 2016;102:1486– 1493.

•44 european hospitals
•8647 patients ,mean age was 62.0 ± 10.4 years,men 88.5%
•Mean clinical follow-up duration was 24.7 ± 15.0 months
Galassi, Sianos et al JACC 2015, vol 65, n 22

Galassi, Sianos et al JACC 2015, vol 65, n 22
Changes in angina and dyspnea status after retrograde CTO PCI

J Am Heart Assoc. 2016;5
619 CTO PCI performed in 7 US
centers
In 38 % patients was used intravascular
imaging (IVUS in 36%, OCT in 3%, and
both in 1.45%)

Morphological assessment of CTO:coronary CT
angiography and IVUS
128 patients, 130 lesions analyzed with coronary CT angiography and IVUS
Positive
remodelling
(33.8%)
Negative
remodelling
(56.9%)
Collapse
(9.2%)
Yamamoto et al
Eur Heart Cardiovasc
Imaging. 2016 Apr

Yamamoto et al Eur Heart J Cardiovasc Imaging. 2016 Apr 20
Positive remodelling
(n=44)
Negative remodelling
(n=74)
Collapse
(n=12)
P value
Median age (years) 64.5 (51.3-71) 67 (58-75.3) 55 (49.5-61.8) 0.005
Occlusion length (mm) 10.4 (5.5-17.4) 10.7 (6.0, 20.5) 46.3 (19.0, 61.0) <0.001
IVUS remodelling index 1.24 (1.14, 1.33) 0.97 (0.80, 1.02) 0.89 (0.53, 0.95) <0.001
Proximal plaque burden 53.1 (46.2, 62.6) 59.1 (50.6, 65.0) 40.5 (31.5, 47.5) 0.001
Distal plaque burden 51.2 (38.9, 58.0) 57.1 (47.0, 65.6) 34.1 (21.4, 39.1) <0.001
Stent expansion (%) 96.2 94.8 91.3 0.76
Retrograde approach (%) 25 36.5 66 0.03
34%
57%
9%
29%
40% 29% 41%
33%
25%
Plaque type
= non-calcified= mixed = calcified

Am J Cardiol. 2016 Mar 1;117(5):727-34
 serial follow-up intravascular ultrasound (baseline and follow-up at 9 ± 2 months)
after DES implantation into 40 CTOs.
anterograde approach (82.5%), retrograde approach (17.5%)
Late-acquired stent malapposition
was seen in 17 patients (42.5%)
In 8 CTOs (20%), a part of the stent
was implanted into a subintimal
space; in these 8 patients, maximum
percent neointimal hyperplasia and
minimum lumen area was similar in
the subintimal segment compared
with the adjacent intraplaque
segment. The frequency of late-
acquired stent malapposition was
similar

The distal reference, but not the
proximal reference lumen CSA,
increased significantly at follow-up
(3.8 ± 2.0 to 5.1 ± 2.3 mm(2), p =
0.0004)
Conclusion: after CTO treatment with DES, distal vessel enlargement was detected.
Subintimal stenting after recanalization of CTO was not inferior compared with
stenting within the plaque in terms of long-term morphologic impact
Am J Cardiol. 2016 Mar 1;117(5):727-34

230 pts with CTO randomized 1:1 IVUS+angiography vs angiography
EuroIntervention 2015;10:1409-1417
The primary endpoint
was in-stent late
lumen loss (LLL) at
one-year follow-up.
Follow-up with office
visits or telephone
contact to 24 months

 In-stent LLL in the IVUS-guided group was significantly lower compared to the angiography-guided
group at one-year follow-up (0.28±0.48 mm vs. 0.46±0.68 mm, p=0.025), with a significant
difference in restenosis of the "in-true-lumen" stent between the two groups (3.9% vs.13.7%,
p=0.021)
 The minimal lumen diameter and minimal stent cross-section area significantly and negatively
correlated with LLL (all p<0.001).
 The rates of adverse clinical events were comparable between the IVUS- and angiography-guided
groups at two-year follow-up (21.7% vs. 25.2%, p=0.641).
EuroIntervention 2015;10:1409-1417

Circ Cardiovasc Interv. 2015 Jul;8(7):
N-BES, Nobori biolimus
eluting stent;
R-ZES,Resolute
zotarolimus-eluting
stent

Circ Cardiovasc Interv. 2015 Jul;8(7):
IVUS-guided CTO intervention significantly improved MACE rate during the
12 months after DES implantation when compared with conventional
No significant differences zotarolimus and biolimus eluting stents

Kelbæk et al, EuroIntervention 2015;11:650-657
3 groups: - chronic TO (CTO; n=256)
- non-chronic TO (n=292)
- no occlusion (n=2.941)
Resolute zotarolimus-eluting stent (R-ZES)

The rate of TLF at two years was not significantly different among patients in the
CTO (9.1%), TO (9.8%), and no occlusion (10.4%) groups (log-rank p=0.800);
neither were the components of TLF
Definite or probable stent thrombosis occurred more frequently in the TO group
(2.8% vs. 1.2% in the CTO and 1.1% in the group with no occlusion, p=0.027).
There were 10 late and six very late stent thrombosis events
Conclusions
Apart from a higher rate of stent thrombosis in patients with TO, patients with
totally occluded coronary arteries who receive revascularisation with an R-ZES
have clinical outcomes comparable to those who receive a similar stent in non-
occluded lesions
Kelbæk et al, EuroIntervention 2015;11:650-657

Teewen et al Eurointervention 2014
First phase : randomized 51 pts SES vs 46 pts Endeavor (zotarolimus)
Second phase: randomized 103 patients SES vs 104 patients Resolute (zotarolimus)
First phase NO significative differences
target lesion revascularisation 12.2% vs. 19.6%, p=0.4
target vessel failure 14.3% vs. 19.6%, p=0.68
definite or probable stent thrombosis 4.1% vs. 2.2%
Second phase NO significative differences
target lesion revascularisation 10% vs. 5.9%, p=0.42
target vessel failure 10% vs. 7.9 %, p=0.78
definite or probable stent thrombosis 1% vs. 0%
Target vessel failure

First-Generation Versus Second-Generation DES in
CTO: Two-Year Results of a Multicenter Registry
Ahn …Choi, August 2016

Efficacy of second-generation DES is similar to
that of first-generation DES for patients with CTO

Everolimus- Versus Sirolimus- Versus Paclitaxel-
Eluting Stents in OCT
National Korean registry
Primary endpoint: MACE (composite of cardiac death, nonfatal
myocardial infarction, and target lesion revascularization)
Each component of MACE was also comparable
among the 3 stents.
Independent predictors of MACE were diabetes
mellitus, previous congestive heart failure, and
left circumflex CTO.

• 40 consecutive patients with CTO treated with BVS
• Population : male 78%, mean age 59.9±8.3 years, diabetics 30%
• Mean J-CTO score was 1.6.
• Results: a total of 63 BVS were implanted with an average number of
1.6 per patient, and an average scaffold length of 42.4±21.5 mm.
• No device-related complications.
• At follow-up (median time 556 days): no deaths, one late scaffold
thrombosis , one focal restenosis
EuroIntervention 2016;12:e144-e151

• CTO Prevalence is increasing in the sicker, older patients studied
angiographically nowadays and depends on patient
characteristics: it may reach up to 40% in diabetes/ischemic HF
with low EF
• New comparisons of successful and failed CTO revascularization
suggest improvement of long term prognosis
• New predicting scores for estimating technical success in CTO
PCI offer limited advantage over J-CTO
• Standardization of modern CTO recanalization techniques,
achieves success rates approaching 90%
• Intravascular image can facilitate CTO PCI but is rarely used
• Type of DES have limited influence in MACE post CTO
recanalisation, with insufficient data to recommend BVS
Conclusions
EuroCTO Course 2015-2016 :
Rapid Review of the Recent CTO Literature

Carlo Di Mario - Recent Publications & Research in CTO: 2015-16

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