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Dobric et al. Vessel Plus 2019;3:26 I http://dx.doi.org/10.20517/2574-1209.2018.77 Page 3 of 7

Traditionally, antegrade approach is used as a first strategy of CTO recanalization. With the development
of new guidewires, microcatheters, the single wire techniques, parallel-wire technique, techniques with
subintimal tracking, and antegrade dissection and reentry technique, it remained the most common
first choice strategy. Retrograde techniques were developed over long period of time, and made major
breakthrough in mid 2000s with the pioneering work of Dr Osamu Katoh who introduced the Controlled
Antegrade and Retrograde subintimal Tracking technique of retrograde CTO recanalization. Detailed
consideration of choosing between antegrade and retrograde strategies is beyond the scope of this review,
[13]
and may be found elsewhere . It is worth mentioning few more aspects specific to PCI for CTO. In a
recently published report from OPEN-CTO registry, major complication rates still remain significant and
higher than in non-CTO PCI: in-hospital/one-month mortality was 0.9% and 1.3%, respectively, while
[14]
coronary perforations requiring treatment occurred in 4.8% of patients . Operators should be aware of
contrast toxicity and should limit the contrast volume to minimum needed and adjusted to renal function
of the patient. Radiation safety is an important issue and physicians should make every effort to reduce
radiation exposure, and to document radiation exposure during a PCI procedure.

Symptomatic and prognostic impact of the PCI for CTO
Despite these truly amazing technical improvements in achieving proficiency of CTO recanalization, many
aspects of clinical efficacy of this demanding procedure remain controversial. Several non-randomized
(observational) trials have shown that successful CTO revascularization could be linked to improved
cardiovascular outcomes [15-17] and better quality of life (QOL) [18,19] . We have recently published a long
[20]
term (66 months) follow-up of cohort of 283 patients in whom recanalization of CTO was attempted .
Patients with successfully recanalized CTO had lower rate of MACE (defined as composite of cardiac
mortality, myocardial infarction, and target vessel revascularization) than patients with failed procedure;
the difference that remained statistically significant after adjustment for baseline between-group differences
[21]
using propensity scores (adjusted HR 0.402; 95%CI: 0.196-0.824; P = 0.013). Christakopoulos et al.
published a review of 25 observational trials and showed improved outcomes with successful PCI of the
CTO (which included survival, angina severity, and the need for coronary artery bypass surgery). Having
in mind all limitation of these kind of trials, no causal inferences could be drawn between PCI for CTO
and positive cardiac outcomes. These conclusions may be regarded only as a hypothesis generating, and
must be checked in appropriately designed randomized controlled clinical trials (RCTs). Only RCTs could
answer questions related to causality between the procedure and outcomes, and we have data from few of
them recently published.

The EXPLORE (Evaluating Xience and Left Ventricular Function in PCI on Occlusions After ST-Elevation
Myocardial Infarction) study randomized 304 patients presented as STEMI which also had a CTO lesion in
[22]
a non-infarct artery to additional PCI of CTO soon after primary PCI or optimal medical therapy only .
Primary endpoints were left ventricular ejection fraction (LVEF) and left ventricular end diastolic volume
(LVEDV) on cardiac MRI after 4 months. Authors did not report any benefit for CTO PCI in terms of
LVEF (44.1% ± 12.2% vs. 44.8% ± 11.9%; P = 0.60) or LVEDV (215.6 ± 62.5 mL vs. 212.8 ± 60.3 mL; P =
0.70). Furthermore, they did not find the difference in terms of major adverse coronary events (5.4% vs.
2.6%; P = 0.25). It was suggested that PCI of the CTO in LAD artery could be related to improved LVEF
(47.2% ± 12.3% vs. 40.4% ± 11.9%; P = 0.02), but this finding remained hypothesis-generating. Even during
prolonged follow-up (median of 3.9 years) of this trial, MACE did not differ between arms (13.5% vs.
12.3%, HR 1.03, 95%CI: 0.54-1.98; P = 0.93). Interestingly, reported cardiac mortality was higher in the
CTO-PCI arm (6.0% vs. 1.0%, P = 0.02), while there was no difference in all-cause mortality (12.9% vs.
[23]
6.2%, HR 2.07, 95%CI: 0.84-5.14; P = 0.11) .

Another randomized trial (the REVASC trial) assessed the effect of CTO recanalization on segmental wall
thickening (SWT) (the primary endpoint) and improvement of regional wall motion and changes in left