EuroIntervention EXPERT CONSENSUS

2024;20:e174-e184
published online e-edition February 2024
DOI: 10.4244/EIJ-D-23-00749

Evaluation and management of patients with coronary chronic total

occlusions considered for revascularisation. A clinical consensus
statement of the European Association of Percutaneous
Cardiovascular Interventions (EAPCI) of the ESC, the European
Association of Cardiovascular Imaging (EACVI) of the ESC, and the
ESC Working Group on Cardiovascular Surgery
Alfredo R. Galassi1*, MD; Giuseppe Vadalà1 , MD; Gerald S. Werner2 , MD, PhD; Bernard Cosyns3 , MD, PhD;
Georgios Sianos4 , MD, PhD; Jonathan Hill5, MD; Dariusz Dudek6 , MD, PhD; Eugenio Picano7 , MD, PhD;
Giuseppina Novo1, MD, PhD; Daniele Andreini8, MD, PhD; Bernhard L.M. Gerber9, MD, PhD;
Ronny Buechel10, MD; Kambis Mashayekhi11, MD, PhD; Mathias Thielmann12, MD;
Margaret McEntegart13, MD, PhD; Beatriz Vaquerizo14, MD, PhD; Carlo Di Mario15, MD, PhD;
Sinisa Stojkovic16, MD, PhD; Sigrid Sandner17, MD, PhD; Nikolaos Bonaros18, MD, PhD;
Thomas F. Lüscher5,19, MD, PhD
*Corresponding author: University of Palermo, Via del Vespro 129, 90127, Palermo, Italy. E-mail: alfredo.galassi@unipa.it
The authors’ affiliations can be found at the end of this article.

Chronic total occlusions (CTOs) of coronary arteries can be found in the context of chronic or acute coronary
syndromes; sometimes they are an incidental finding in those apparently healthy individuals undergoing imaging
for preoperative risk assessment. Recently, the invasive management of CTOs has made impressive progress due to
sophisticated preinterventional assessment, including advanced non-invasive imaging, the availability of novel and
dedicated tools for CTO percutaneous coronary intervention (PCI), and experienced interventionalists working in
specialised centres. Thus, it is crucial that referring physicians who see patients with CTO be aware of recent devel-
ABSTRACT

opments and of the initial evaluation requirements for such patients. Besides a careful history and clinical examina-
tion, electrocardiograms, exercise tests, and non-invasive imaging modalities are important for selecting the patients
most suitable for CTO PCI, while others may be referred to coronary artery bypass graft or optimal medical therapy
only. While CTO PCI improves angina and reduces the use of antianginal drugs in patients with symptoms and
proven ischaemia, hibernation and/or wall motion abnormalities at baseline or during stress, the effect of CTO PCI
on major cardiovascular events is still controversial. This clinical consensus statement specifically focuses on refer-
ring physicians, providing a comprehensive algorithm for the preinterventional evaluation of patients with CTO and
the current evidence for the clinical effectiveness of the procedure. The proposed care track has been developed by
members and with the support of the European Association of Percutaneous Cardiovascular Interventions (EAPCI),
the European Association of Cardiovascular Imaging (EACVI), and the European Society of Cardiology (ESC)
Working Group on Cardiovascular Surgery.

KEYWORDS: chronic coronary total occlusion; left ventricular dysfunction; Heart Team; multiple vessel disease; stable angina

e174 © Europa Digital & Publishing 2024. All rights reserved. SUBMITTED ON 01/09/2023 - REVISION RECEIVED ON 1st 16/10/2023 / 2nd 02/11/2023- ACCEPTED ON 05/11/2023
 Evaluation and management of CTO patients

T
he management of coronary chronic total occlu- In both circumstances, it is desirable to carefully evaluate
sions (CTOs) is clinically and technically challenging the patient’s age, frailty, and comorbidities (e.g., significant
and requires a close collaboration between refer- concomitant valvular heart disease, large aortic aneurysms,
ring physicians and specialised centres1. The therapeutic non-cardiac limitations of functional capacity, ongoing onco-
options for patients with CTOs have expanded immensely logical treatment and/or cognitive deficits, among others).
thanks to sophisticated preinterventional planning, includ- These clinical elements should concur with technical consid-
ing advanced cardiac imaging, advanced percutaneous cor- erations to guide the decision between OMT or revasculari-
onary intervention (PCI) equipment, cardiac surgery, and sation and, in the latter group, between PCI and surgery. Of
effective anti-ischaemic optimal medical therapy (OMT). note, patients with CTO are older, more often diabetic and
Because of these developments, the success rate of CTO with a greater impairment of left ventricular ejection fraction
PCI today exceeds 80-90% in the hands of expert operators (LVEF), compared with patients without CTO6.
working at specialised CTO referral centres2,3. According Other patients may present with ACS, including ST-segment
to the CTO Academic Research Consortium (CTO-ARC), elevation myocardial infarction (STEMI). In the case of type
a CTO is defined as an occlusion of an epicardial coronary 1 myocardial infarction (MI), with either a plaque rupture or
artery without antegrade flow through the lesion and with erosion in the culprit artery providing collaterals to another
a probable or definite duration of ≥3 months, based on coronary artery with a CTO, prognosis is poor because of
angiographic criteria such as a Thrombolysis in Myocardial the double injury due to interruption of collateral flow from
Infarction (TIMI) grade 0 flow through the lesion with no the culprit artery to the CTO territory7. Notably, about
evidence of a thrombus, no staining at the proximal cap, one-third of patients who are resuscitated because of a car-
and the presence of mature collaterals4. Contemporary, diac arrest have a CTO8. If severe acute ischaemia has led
consecutive series of patients undergoing invasive coronary to cardiogenic shock, complete revascularisation beyond the
angiography (ICA) reported the presence of at least one infarct-related artery should be avoided. Indeed, the initial
CTO in 15-20% of cases5,6. suggestion of the SHOCK trial that complete revascularisa-
However, the decision-making process for the management tion should be attempted in this setting was refuted by later
of such patients requires a thorough clinical evaluation with trials9,10. Conversely, there is convincing evidence supporting
initial examinations including electrocardiograms (ECGs), complete revascularisation for STEMI without cardiogenic
echocardiography, exercise tests, or cardiac imaging stress shock and multivessel disease11. However, these trials were
tests. not specifically targeted for patients with CTO in non-culprit
This clinical consensus statement, involving the European arteries (Table 1).
Society of Cardiology (ESC) Association of Percutaneous Patients with non-STEMI-ACS also require immediate
Cardiovascular Interventions (EAPCI), the ESC Association treatment of the culprit artery, with the added challenge of
of Cardiovascular Imaging (EACVI), as well as the ESC ruling out the CTO as the cause of or contributor to the
Working Group on Cardiovascular Surgery, proposes a com- acute event12 (Table 1). Besides clinical clues, the absence of
prehensive algorithm for patients in whom a CTO has been contrast staining, which is typical of fresh thrombotic occlu-
diagnosed, providing a preinterventional evaluation targeted sions, and the presence of well-developed collaterals towards
to the patient’s condition and needs. the distal segment of the CTO normally allow a distinction
between acute and chronic coronary occlusions. A particu-
The CTO patient: characteristics and clinical larly interesting subgroup includes patients with type 2 MI
phenotypes (i.e., MI secondary to ischaemia due to either increased oxy-
CTOs may be discovered in different clinical settings, such as gen demand or decreased supply). They typically present with
acute coronary syndromes (ACS), in the context of chest pain increased troponin levels, ECG changes and/or regional wall
evaluation, as a consequence of documented ischaemia using motion abnormalities, with or without symptoms1,13. In such
different imaging modalities1 or incidentally, during a coro- cases, the treatment should focus on the acute trigger disrupt-
nary angiography workup before surgical valve replacement ing a previously stable situation with no immediate need of
or vascular surgery, among others1,5,6. While patients com- an urgent or emergent CTO revascularisation, but with con-
plaining of exertional symptoms (e.g., angina, dyspnoea) sideration of it at a later stage (Table 1).
have a clear diagnostic and therapeutic path to be followed,
asymptomatic patients must be carefully evaluated based on Initial examination
further examinations usually not available to the treating The main indication for CTO recanalisation is to relieve
physician at the time of presentation (Figure 1). exercise-limiting symptoms such as angina. Thus, the initial

Abbreviations
ACS acute coronary syndromes ECG electrocardiogram PCI percutaneous coronary intervention
CABG coronary artery bypass grafting LVEF left ventricular ejection fraction STEMI ST-segment elevation myocardial
CTCA computed tomography coronary MACE major adverse cardiovascular events infarction
angiography MI myocardial infarction VA ventricular arrhythmias
CTO chronic total occlusion MRI magnetic resonance imaging

EuroIntervention 2024;20:e174- e184 • Alfredo R. Galassi et al. e175

 Figure 1. Different clinical presentation modalities of patients with coronary CTO. The CTO may be discovered in symptomatic
patients in the context of stable angina with or without signs/symptoms of heart failure, ACS, troponin rise and/or ECG/
echocardiographic changes during supraventricular arrhythmias, after acute bleedings or during/after a non-cardiac operation
(type 2 MI). In asymptomatic patients, a CTO may be detected as an incidental finding after CTCA or a positive stress test.
ACS: acute coronary syndrome; CT: computed tomography; CTCA: computed tomography coronary angiography;
CTO: chronic total occlusion; ECG: electrocardiogram; LAD: left anterior descending artery; MI: myocardial infarction;
RCA: right coronary artery

clinical examination requires a comprehensive and careful angina and/or dyspnoea, and their reproducibility compared
assessment of the symptomatic status, as well as possible to the patient’s history.
changes in the customary exercise levels over the past months Furthermore, many patients may have silent ischaemia in
or years, taking in account that, often, CTO patients may the CTO territory as well. In such cases, collaterals com-
adapt to their limited exercise capacity and may not perceive monly prevent regional myocardial dysfunction or MI,
or report their functional status limitation appropriately. but their functional capacity to increase myocardial blood
Furthermore, symptoms are not limited to chest pain only; flow to the CTO territory during exercise may be limited.
indeed, dyspnoea is at least as frequent as angina, and this Typically, fractional flow reserve (FFR) assessed distal to
improves after successful recanalisation14. a CTO is usually below 0.520,21. Thus, the use of non-inva-
The assessment of exercise-induced symptoms can be sive ischaemia tests should be strongly encouraged, especially
objectively performed in a “patient-centred” fashion, using in patients with atypical symptoms or in those complaining
tools such as the modified Seattle Angina Questionnaire of dyspnoea, to ascertain their ischaemic origin. Finally, in
(SAQ)15, the EuroQol quality-of-life 5-dimensional score (EQ- asymptomatic patients with left ventricular (LV) dysfunction,
5D)16 or Rose Dyspnea Scale (RDS)17 (Figure 2). Depression the assessment of inducible ischaemia/viability may have
may also be more prevalent in patients with CTO18 and may a prognostic value22 and might be considered during follow-
mask exercise-related symptoms. After blood tests, ECGs and up to guide coronary revascularisation in selected cases only
echocardiography, different imaging modalities are useful to (Central illustration).
assure that an angiographically documented CTO serves via- If ischaemia leads to regional wall motion abnormalities,
ble myocardium and indeed induces significant ischaemia dur- as assessed by imaging, the functional recovery of LV func-
ing stress19 (Central illustration). If an imaging stress test is not tion depends on the extent of hibernating or stunned, but
feasible or locally unavailable, a bicycle or treadmill exercise viable, myocardium. However, the evaluation of hiberna-
tolerance test might be carried out to determine the patient’s tion or stunning in patients with CTO has led to conflicting
true functional capacity, the severity of exercise-induced results23-26 (Table 1).

e176 EuroIntervention 2024;20:e174- e184 • Alfredo R. Galassi et al.

 Evaluation and management of CTO patients

Table 1. Expert panel statements.

Evidence available
RCTs and registries:
The CTO recanalisation success rate has dramatically increased (85-90%), provided that expert operators
uncontroversial2,3,5,6,25,26,29,48,49,54-
are offered the full availability of dedicated interventional tools. 56, 59,60

Frequency and severity of complications is higher (1-3%) compared with most PCI procedures in CCS. This
Registries and meta-analyses:
requires careful consideration of the benefit and risk balance before embarking upon CTO recanalisation or
uncontroversial2,3,5,6,25,48,49
moving to recanalisation modalities (ADR, retrograde) that pose higher complication risks.
A specific consent form listing the differences with other PCI procedures (duration, double access, lack of
certainty of success, slightly higher risk of complications) should be submitted to patients and discussed Expert consensus
with the main operator before the procedure.
Ad hoc CTO PCI (i.e., during the same diagnostic angiogram) is discouraged. CTO PCI should be started
only after having ensured that sufficient time is available, experienced operators are present and a well-
defined strategy has been developed. The treating physicians will have the opportunity to review indications, Expert consensus
perform additional tests if needed, and inform the patient and his family, leaving enough time for
decision-making.
The complexity of CTO procedures can be graded, and the most complex (stumpless, ostial, very calcified,
or long and tortuous, previously failed) should be reserved for dedicated operators or performed with Expert consensus
proctorship.
The presence of a CTO during ACS (especially STEMI) increases the risk that the patient develops
Randomised trials9,10,11
cardiogenic shock, but attempts at recanalisation in the acute phase should be discouraged.
Randomised trial11. Expert
Complete revascularisation appears beneficial in STEMI and, with less compelling evidence, in NSTEMI.
consensus on timing and
CTO PCI during primary angioplasty should be discouraged.
modalities of CTO treatment
In CCS patients with multivessel disease with clinical or anatomical preference for PCI over CABG, the
timing of CTO PCI and the sequence of treatment of non-CTO and CTO lesions deserve careful Expert consensus
consideration.
Symptoms of angina or dyspnoea likely caused by the persistence of a CTO and resistant to medical therapy Randomised trials and registries
should be the main driver of CTO recanalisation. 51-55

Myocardial revascularisation decision, in the context of left main/multivessel disease, including CTO lesions, ESC and ACC guidelines on
is optimised by a Heart Team approach. myocardial revascularisation43,44
Current evidence does not support the use of CTO PCI to improve prognosis (reduce mortality and incidence Consensus that the conflicting
of myocardial infarction). Randomised trials have limitations in terms of sample size, patient selection bias evidence from randomised trials
and trial design, and it is worth noting the opposite results in large, nationwide, long-term registries and large registries51-61 is still
comparing patients who had successful or failed CTO with those patients undergoing revascularisation or insufficient to draw firm
left under medical treatment. conclusions
Evidence from meta-analyses24
Current evidence is still not sufficient to draw firm conclusions on the use of CTO PCI to improve left and registries25,32 was not
ventricular function. confirmed in a randomised64
trial
The assessment of inducible ischaemia and viability in the CTO territory is advisable in case of LV
dysfunction. MRI, if available, should be preferred over nuclear tests and stress echocardiography for Expert consensus
viability assessment.
ACC: American College of Cardiology; ACS: acute coronary syndromes; ADR: antegrade dissection and re-entry; CABG: coronary artery bypass grafting;
CCS: chronic coronary syndrome; CTO: chronic total occlusion; ESC: European Society of Cardiology; LV: left ventricular; MRI: magnetic resonance
imaging; NSTEMI: non-ST-segment elevation myocardial infarction; PCI: percutaneous coronary intervention; RCT: randomised controlled trials;
STEMI: ST-segment elevation myocardial infarction

One aspect that is often not routinely evaluated is the the amount of inducible ischaemia, and the viability of the myo-
incidence of ventricular arrhythmias (VA) in patients with cardial segments supplied by it as a basis for decision-making
CTO and ischaemic cardiomyopathy. Indeed, among and for procedural guidance, and eventually to predict the effect
patients with VA on admission, the presence of a coronary of CTO revascularisation on LV remodelling and/or residual
CTO is independently associated with increased midterm ischaemia at follow-up (Table 2).
all-cause mortality27. Furthermore, among patients with This section provides practical advice regarding the use of
ischaemic cardiomyopathy and an implantable cardioverter- all these different imaging modalities, alone or in combina-
defibrillator (ICD) for secondary prevention of sudden tion, each of them with their advantages and weaknesses.
cardiac death (SCD), the presence of an angiographically
documented CTO is an independent predictor of appropri- LV STRUCTURE AND FUNCTION
ate ICD therapy28. The primary goal of assessing left ventricular function is
risk assessment for a planned CTO procedure because com-
Imaging plications increase as LVEF decreases29. Echocardiography,
A comprehensive imaging workup in patients with CTO ideally especially if refined with myocardial strain imaging, is the
aims at defining the anatomy of the involved coronary artery, first choice due to its wide availability30. Furthermore,

EuroIntervention 2024;20:e174- e184 • Alfredo R. Galassi et al. e177

 EuroIntervention Central Illustration

Flowchart of patients with CTO.

Alfredo R. Galassi et al. • EuroIntervention 2024;20:e174- e184 • DOI: 10.4244/EIJ-D-23-00749

*see Table 2 for inducible ischaemia/viability cutoff of each imaging modality. § E.g., young patients, with proximal LAD CTO,
and demonstration of significant silent inducible ischaemia and viability. CCS: Canadian Cardiovascular Society; CTO: chronic
total occlusion; EQ-5D: EuroQol five-dimensional; LV: left ventricular; MRI: magnetic resonance imaging; OMT: optimal
medical therapy; QoL: quality of life; RDS: Rose Dyspnea Scale; SAQ: Seattle Angina Questionnaire

echocardiography can rule out other possible concomitant all-cause death and non-fatal myocardial infarction as com-
pathologies, such as heart valve disease or aortic aneurysms, pared with those with significant residual perfusion defect.
that must be considered before coronary revascularisation. Moreover, long-term cardiac symptom relief was associated
with normalisation of hyperaemic myocardial blood flow
ISCHAEMIA QUANTIFICATION AND MYOCARDIAL VIABILITY (hMBF) levels after CTO PCI33. Stress cardiac magnetic res-
The revascularisation of a CTO should only be indicated if onance imaging (cMRI) perfusion, using a gadolinium-based
the myocardial segments supplied by it are viable and ischae- contrast agent and pharmacological vasodilation, is cur-
mic upon pharmacological stress or exercise. rently considered state-of-the-art for detecting ischaemia and
Nowadays, many different imaging tests can be used for viability, providing precise information about fibrosis and
these purposes, each of them with advantages and drawbacks scarring34,35. Indeed, after successful revascularisation, myo-
(Table 2). However, the local availability of such technolo- cardial contractility recovery of those segments supplied by
gies and the local imagers’ expertise can drive the preferential the CTO vessel is likely if transmurality of late gadolinium
choice of one test over another. enhancement (LGE) is <25%, while it is very unlikely if LGE
Patients with a large area of viable and ischaemic myocar- is >75%. Unfortunately, for segments in the intermediate
dium are likely symptomatic and would likely derive bene- range, the predictive accuracy of LGE transmurality is lim-
fit from CTO revascularisation; conversely, minor degrees of ited; this aspect might explain why successful CTO PCI of
ischaemia commonly respond well to OMT31,32. Furthermore, a dysfunctional but viable myocardium does not lead to the
patients with extensive ischaemic burden reduction and expected left ventricular function recovery in all patients35,36.
no residual ischaemia after CTO PCI have lower rates of Beyond cMRI, stress echocardiography is widely used for the

e178 EuroIntervention 2024;20:e174- e184 • Alfredo R. Galassi et al.

 Evaluation and management of CTO patients

Figure 2. Definition of CTO revascularisation. Except for cases of isolated non-LAD CTO, the Heart Team must endorse the
most appropriate revascularisation modality. CABG: coronary artery bypass grafting; CT: computed tomography; CTO: chronic
total occlusion; EuroSCORE: European System for Cardiac Operative Risk Evaluation; J-CTO: Japanese Multicenter CTO
Registry; LAD: left anterior descending artery; MVD: multivessel disease; PCI: percutaneous coronary intervention; STS: Society
of Thoracic Surgeons

Table 2. Evaluation of myocardial ischaemia and viability by different imaging modalities.

Inducible ischaemia Myocardial viability Limitations
ECHO • Stress-induced wall motion • Low-dose dobutamine/low-load exercise
abnormalities in >3 out of 17 echo wall motion abnormalities • Image quality
segments improvement in >3 out of 17 segments • Reproducibility
• Stress-induced perfusion defect with • Reversibility of rest or stress-induced • Reduced sensitivity for viability
contrast echo in >3 out of 17 perfusion defect with contrast echo in assessment
segments >3 out of 17 segments
CMR • Stress-induced wall motion • Low-dose dobutamine/low-load exercise • Availability
abnormalities in ≥3 out of 16 echo wall motion abnormalities • Time-consuming
segments improvement in ≥3 out of 16 segments • Not suitable for patients with
• Stress-induced perfusion defect in ≥2 • LGE <25-50% transmurality in >4 out claustrophobia
out of 17 segments of 17 segments • Costs
SPECT and PET • Stress-induced SPECT Tc-99m: >10%
of global myocardium area • [18F]FDG PET resting uptake ≥50%
• Ionising radiation exposure
• Pharmacologically induced [150] •2 01-T1 or Tc-99m SPECT resting
• Time-consuming
H20- or [13N]-ammonia PET imaging uptake >50%
in >3 out of 17 segments
CTCA • Stress-induced perfusion defect with
•P
 erfusion CT <75% transmurality in >3 • Ionising radiation exposure
contrast
out of 17 segments • Ventricular performance
• FFR-CT <0.8
CMR: cardiac magnetic resonance imaging; CT: computed tomography; CTCA: computed tomography coronary angiography; ECHO: echocardiography;
FDG: fluorodeoxyglucose; FFR-CT: fractional flow reserve computed tomography; LGE: late gadolinium enhancement; PET: positron emission tomography;
SPECT: single-photon emission computed tomography

EuroIntervention 2024;20:e174- e184 • Alfredo R. Galassi et al. e179

 assessment of myocardial viability and inducible ischaemia PCI (Table 1). Finally, the patient should be aware that while
with treadmill exercise or dobutamine protocols. However, a symptomatic improvement or a reduction in antianginal
dobutamine echocardiography, besides its high specificity, drugs are both plausible, there is not sufficient evidence to
showed reduced sensitivity in predicting the recovery of dys- suggest that the CTO revascularisation will prolong their sur-
functional myocardium supplied by totally occluded vessels37. vival or decrease the risk of major adverse CV events at fol-
Finally, among nuclear tests, positron emission tomography low-up (Table 1).
(PET) should be the preferred technique for the myocardial
viability assessment due to its higher spatial and temporal res- Clinical outcomes
olution, lower radiation dose, and shorter scan duration than Despite the high prevalence of CTO and the higher CV risk
single-photon emission computed tomography (SPECT)38. associated with it, CTO recanalisation traditionally represents
only a small fraction of the overall volume of PCIs46. In the
GUIDANCE FOR PROCEDURAL PLANNING past, this was mainly due to a combination of low success
For a definitive diagnosis of CTO, coronary angiography rates, high incidence of complications, long procedural times,
remains the gold standard. Thus, for guidance of procedural high costs and perceived lack of clinical benefit. However,
planning, a dual coronary angiography should be performed in the last decade, along with an increased revascularisa-
unless coronary collateral circulation originates exclusively tion success rate2,3, the pooled estimate of complication rates
from the ipsilateral vessel39. However, coronary computed has decreased over time, now at a maximum of 3%, yet still
tomography (CT) scans, particularly with three-dimensional remaining higher than that of non-CTO PCI47,48.
reconstructions, are used more and more frequently, provid- Given this, the most important questions to be answered
ing important complementary information to the conventional after PCI-based CTO revascularisation are the following:
coronary angiography (location and extent of calcification, 1) Is there any improvement in angina, exercise capacity
definition of morphology of proximal and distal CTO caps, and/or quality of life?
occlusion length, CTO tortuosity) especially in very com- 2) Is there any reduction in major adverse cardiovascular
plex CTOs40. Such anatomical information may influence the events (MACE) at long-term follow-up?
PCI strategy and material selection for PCI. For example, in 3) What is the role of CTO revascularisation in patients
cases of heavily calcified lesions, the use of calcium modifi- with left ventricular dysfunction?
cation treatment (e.g., rotational atherectomy or intravascular
lithotripsy), as well as the vessel course in a very long CTO SYMPTOMS, QUALITY OF LIFE AND FUNCTIONAL STATUS
segment, can be anticipated. Furthermore, a computed tomog- In stable coronary artery disease, the prevalence of angina,
raphy coronary angiography (CTCA)-derived score, such as the despite OMT, was approximately 20% in one of the largest
Computed Tomography Registry of Chronic Total Occlusion contemporary European registries where anginal symptoms
Revascularization (CT-RECTOR), was shown to be more were associated with an increased risk of MACE, including
accurate than the angiography-based Japanese Multicenter cardiovascular death and non-fatal MI49. Furthermore, a non-
CTO Registry (J-CTO) score for grading CTO difficulty before negligible proportion of patients still complained of refractory
PCI, as assessed by the time-efficient guidewire crossing41,42. angina despite multiple CABGs and/or PCIs1. Besides OMT
and revascularisation of non-CTO lesions, CTO PCI repre-
Decision-making: the Heart Team sents an additional tool for symptom relief and improvement
Both European and American guidelines recommend the in quality of life50,51.
concept of an interdisciplinary Heart Team involving car- Recently, the OPEN-CTO registry demonstrated that
diac surgeons, interventional and general cardiologists, CTO PCI improved patients’ health status, as assessed
cardiovascular (CV) imagers and anaesthesiologists for deci- by the SAQ and mean RDS scores at 1-month follow-
sion-making with different levels of evidence43,44. Especially up18. Furthermore, 3 out of the 4 main randomised trials
in those complex scenarios where multiple comorbidi- available on this topic, EuroCTO52, COMET-CTO53, and
ties, advanced patient age, left main and 3-vessel disease, IMPACTOR-CTO54, demonstrated that patients’ health sta-
including CTOs, make the choice of the best treatment tus improved more significantly after CTO PCI than with
option challenging, the Heart Team is of value to endorse OMT, while the DECISION-CTO trial51 did not. In the
the treatment strategy (Figure 2). Indeed, PCI has a low risk EuroCTO trial, patients undergoing PCI for CTO not only
of immediate complications, while coronary artery bypass showed a marked improvement in the SAQ score (angina fre-
grafts (CABGs) showed improved long-term, event-free sur- quency and quality of life) compared to OMT (hazard ratios
vival if an internal mammary artery graft to the left anterior [HR] 5.23 and 6.62, respectively), but also a higher rate of
descending artery is used45. complete freedom from angina (71.6% vs 57.8%; p<0.001)
Beyond the anatomical (e.g., coronary structure, calcifica- and a lower burden of antianginal drugs taken at 1-year fol-
tion, access to occluded segment, among others) and func- low-up52. Similarly, the COMET-CTO trial, at a mean fol-
tional data (i.e., ischaemia and viability) relevant to assess low-up of 275±88 days, showed a significant improvement
the appropriateness of a CTO procedure, the patient’s clinical of symptoms and quality of life measured by the SAQ in the
profile and their wishes also have to be taken into account CTO PCI group compared to the OMT group53. Finally, in
when considering coronary revascularisation of CTOs. The the IMPACTOR-CTO trial, where 94 patients with isolated
patient must be made aware that they will undergo an inter- right coronary artery CTO were randomised, CTO PCI led
vention with a much longer duration and a higher compli- to a significantly greater improvement in the 6-min walk
cation rate (e.g., coronary perforations) than for non-CTO distance and quality of life as assessed by the 36-Item Short

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 Evaluation and management of CTO patients

Form Health Survey (SF-36) at 1-year follow-up, compared especially among patients with more severe LV dysfunc-
with OMT alone54. tion, significant myocardial inducible perfusion defect and
In summary, evidence supporting CTO PCI as an effec- viability, these data were not confirmed in the randomised
tive tool for symptom relief (both angina and dyspnoea) and REVASC trial24,25,32,63. In this study, the mean baseline LVEF
improvement in quality of life is based on several observa- was only mildly/moderately reduced in both the OMT and
tional studies and on 4 randomised controlled trials, of which CTO PCI groups (59.6 [45.8 to 64.3] and 54.7 [42.9 to
3 are in favour of endovascular revascularisation, while one 65.1], respectively), with one possible explanation for this
(DECISION-CTO) was neutral. Based on this, symptoms being the neutral effect of coronary revascularisation on LV
such as angina or dyspnoea, resistant to the best medical recovery (Table 1).
therapy tolerated by the patient, should be the main driver of Similarly, the relationship between LVEF recovery and
CTO recanalisation (Table 1). long-term patient outcomes is still debated (Table 1). In the
REVASC trial, the CTO PCI group showed a higher MACE
MACE REDUCTION AT LONG-TERM FOLLOW-UP rate reduction, as compared with the group managed by
Different observational studies using a propensity score- OMT, driven mostly by lower repeated intervention rate at
matched analysis have demonstrated a lower incidence of 1-year follow-up (16.3% vs 5.9%; p=0.02)63.
MACE after CTO revascularisation as compared with OMT Furthermore, Schumacher et al have recently demonstrated
alone at long-term follow-up55-57. Similarly, two large pro- that while extensive ischaemia reduction after CTO PCI led
spective registries, the Korean registry58 and the Canadian to significantly better survival, free of death and MI, among
Multicenter Chronic Total Occlusion Registry59, showed a sig- patients with LV dysfunction, this was not the case among
nificant clinical benefit of CTO revascularisation over OMT patients with preserved LV function64.
alone at very long-term follow-up. The first is a single-centre, Of course, the present study is not randomised and should
propensity-matched cohort of 1,547 consecutive patients with be considered as hypothesis-generating. Therefore, despite suc-
CTO who underwent either PCI or routine OMT. At 10 years, cessful CTO revascularisation of dysfunctional myocardium
a significant mortality benefit was shown in the CTO PCI not being systematically followed by LVEF recovery, future
group as compared with OMT (13.6% vs 20.8%, HR 0.64; large randomised studies are warranted to conclusively define
p=0.01)58. Similarly, in the Canadian Registry, which enrolled whether CTO revascularisation of patients with severe LV dys-
1,624 patients, CTO revascularisation was associated with function may be beneficial at long-term follow-up. Indeed, this
a lower 10-year incidence of MACE, including all-cause mor- population is not adequately represented in the current studies.
tality (22.7% vs 36.6%), future revascularisation (14.0%
vs 22.8%), and ACS hospitalisation (10.0% vs 16.6%) as Conclusions
compared with OMT59. Similarly, at 3-year follow-up, the Percutaneous CTO interventions have reached a high level of
EuroCTO trial confirmed no differences in the rates of car- success with acceptable complication rates when in the hands
diovascular death or myocardial infarction between PCI or of expert operators. Symptom improvement, on top of medi-
OMT among patients with a remaining single coronary CTO, cal therapy, is the main goal of CTO PCI, while MACE reduc-
but the MACE rate was higher in the OMT group due to tion at follow-up remains uncertain, as the currently available
more ischaemia-driven revascularisations60. trials were underpowered and led to conflicting results.
Conversely, the two other randomised trials, DECISION- A rational patient selection, based on clinical symptoms, dif-
CTO51 and EXPLORE61, did not confirm a long-term MACE ferent imaging modalities and a multidisciplinary approach,
reduction with CTO revascularisation as compared with is key for a successful CTO revascularisation. Finally, in situ-
OMT. However, many caveats exist for both trials, which ations where multiple comorbidities make the choice of the
have been described in detail previously62. best treatment option challenging, the Heart Team is essential
Therefore, although randomised controlled trials provide to endorse the treatment strategy.
the highest level of evidence in the currently used guidelines,
they also have some limitations and give conflicting results. Authors’ affiliations
Moreover, propensity-matched analysis studies and registries 1. Department of PROMISE, University of Palermo,
are prone to undetected bias and often have a lack of an inde- Palermo, Italy; 2. Medical Department I (Cardiology),
pendent MACE adjudication. As such, registries can only be Klinikum Darmstadt GmbH, Darmstadt, Germany;
considered hypothesis-generating. Furthermore, CTO revascu- 3. Cardiology, Universitair Ziekenhuis Brussel, Centrum
larisation compared with OMT now faces fierce competition voor Hart en Vaatziekten, Brussels, Belgium; 4. AHEPA
by effective anti-ischaemic, antithrombotic and hypolipidaemic University General Hospital of Thessaloniki, Thessaloniki,
remedies (Table 1). Nevertheless, further large-scale, randomised Greece; 5. Royal Brompton & Harefield Hospitals GSTT,
trials, with long-term follow-up, including patients with London, United Kingdom; 6. Cardiac Catheterization
depressed LVEF, comorbidities and significant symptoms, are Laboratories, Jagiellonian University Medical College,
needed to determine whether CTO revascularisation is indeed Krakow, Poland; 7. Institute of Clinical Physiology,
superior to OMT in terms of long-term MACE reduction. National Research Council, Pisa, Italy; 8. Centro
Cardiologico Monzino, Milan, Italy; 9. Cardiology
CTO REVASCULARISATION OF PATIENTS WITH REDUCED Department, Cliniques Universitaires St. Luc UCL,
LEFT VENTRICULAR EJECTION FRACTION Brussels, Belgium; 10. Department of Nuclear Medicine,
Although some previous studies have shown LVEF recov- Cardiovascular Imaging, University Hospital of Zurich,
ery after successful revascularisation of the CTO territory, Zurich, Switzerland; 11. Division of Cardiology and

EuroIntervention 2024;20:e174- e184 • Alfredo R. Galassi et al. e181

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