Abstract
A coronary chronic total occlusion (CTO) is defined as a 100% occlusion of an artery with thrombolysis in myocardial infarction (TIMI) 0 flow of at least 3 month duration. CTO is present in 16%–52% of patients with coronary artery disease undergoing coronary angiography. Successful CTO percutaneous coronary intervention (PCI) can provide significant benefits to the patient, including improved quality of life, decreased need for coronary artery bypass graft surgery, reduced need for antianginal medications, improved left ventricular systolic function, reduced risk for arrhythmias, improved tolerance of a future acute coronary syndrome, and possibly lower mortality (in successful vs failed procedures). In the 2011 American College of Cardiology/American Heart Association PCI guidelines, CTO PCI carries a class IIA/level of evidence B recommendation. Absolute contraindications for CTO PCI are inability to receive antiplatelet therapy and prior radiation skin injury to the torso. The decision to proceed with CTO PCI depends on the anticipated benefits and potential risk of the procedures and must be individualized.
Keywords
Appropriateness use criteria, Chronic total occlusion, Contraindications, Guidelines, Indications, Outcomes, Percutaneous coronary intervention, Prevalence
1.1
Chronic Total Occlusion Definition
A coronary chronic total occlusion (CTO) is defined as 100% occlusion in a coronary artery with noncollateral thrombolysis in myocardial infarction (TIMI) 0 flow of at least 3 month duration. The duration of occlusion may be difficult to determine if there has been no prior angiogram demonstrating presence of the CTO. In such cases estimation of the occlusion duration is based upon first onset of symptoms and/or prior history of myocardial infarction in the target vessel territory.
Occluded arteries discovered within 30 days of a myocardial infarction, such as those included in the Open Artery Trial, are not considered to be CTOs. Hence, the lack of benefit observed with percutaneous coronary intervention (PCI) in these subacute lesions should not be extrapolated to CTO PCI.
1.2
Prevalence of Chronic Total Occlusions
Coronary CTOs are common, found in approximately one in three patients undergoing diagnostic coronary angiography ( Table 1.1 ).
| First Author | Country | Year | Number of Sites | n | CTO Prevalence (%) | CTO Prevalence Among Prior CABG Patients (%) |
|---|---|---|---|---|---|---|
| Kahn | United States | 1993 | 1 | 287 | 35 | – |
| Christofferson | United States | 2005 | 1 | 8,004 | 52 | – |
| Werner | Germany | 2009 | 64 | 2,002 | 35 | – |
| Fefer | Canada | 2012 | 3 | 14,439 | 18 | 54 |
| Jeroudi | United States | 2013 | 1 | 1,669 | 31 | 89 |
| Azzalini | Canada | 2015 | 1 | 2,514 | 20 | 87 |
| Tomasello | Italy | 2015 | 12 | 13,423 | 13 | – |
| Ramunddal | Sweden | 2016 | 30 | 89,872 | 16 | – |
Among 14,439 patients undergoing coronary angiography at three Canadian centers, at least one CTO was present in 18.4% of patients with coronary artery disease (CAD). The CTO prevalence was higher (54%) among patients with prior coronary artery bypass graft surgery (CABG) and lower among patients undergoing primary PCI for acute ST-segment elevation myocardial infarction (10%) ( Fig. 1.1 ). Left ventricular function was normal in >50% of patients with CTO and half of the CTOs were located in the right coronary artery. In a Swedish nationwide study and an Italian multicenter registry the prevalence of CTOs among patients with coronary artery disease was 16% and 13%, respectively.
1.3
Should Chronic Total Occlusion Percutaneous Coronary Intervention Be Performed in This Patient?
CTO PCI is a tool in the armamentarium for the treatment of CAD. As with every patient with CAD, treatment of patients with coronary CTOs should include optimal medical therapy (OMT) (every patient should receive aspirin and a statin unless they have a contraindication) and possibly coronary revascularization, with either PCI or CABG.
Revascularization is indicated in patients with angina or other symptoms due to ischemia, such as dyspnea, and possibly patients with ischemia on noninvasive testing, or left ventricular dysfunction ( Fig. 1.2 ). Percutaneous revascularization is preferred in case of single-vessel disease and in post-CABG patients (especially those with patent left internal mammary artery grafts to the left anterior descending artery) due to the high risk and technical challenges associated with redo CABG. In case of multivessel disease, CABG is generally preferred in patients with complex disease (especially if they are diabetic) whereas PCI is preferred in patients with simpler disease.
The decision on whether to perform CTO PCI depends on (1) anticipated benefit and (2) estimated risk .
1.3.1
Estimating Benefit
Potential benefits of CTO PCI depend on (1) clinical presentation (i.e., symptoms, extent of ischemia, myocardial function) and (2) the likelihood of success. Risks include both acute (procedural) and long-term adverse events ( Fig. 1.3 ).
The main demonstrated benefit of CTO PCI is symptomatic improvement. In patients who are truly asymptomatic, CTO PCI is generally not indicated, except possibly in patients with a large area of ischemia (>10%).
CTO patients may have to progressively limit physical activity to prevent symptoms, and often present with atypical symptoms such as dyspnea rather than angina. Therefore, objective evaluation (e.g., with a treadmill stress test, 6-min walking test, standardized quality of life questionnaires, etc.) may be particularly useful in patients with limited or no symptoms.
1.3.1.1
Clinical Determinants of Chronic Total Occlusion Percutaneous Coronary Intervention Benefit
CTO PCI can provide the following benefits:
- 1.
Improve quality of life
For patients with medically refractory angina caused by a CTO, successful CTO recanalization can reduce or eliminate the angina and the need for antianginal medications and improve exercise capacity.
Many patients with coronary CTOs may present with dyspnea and/or fatigue instead of classic angina. Patients with such types of symptoms are frequently miscategorized as asymptomatic, as they can get accustomed to these symptoms and may not report them, or may minimize their severity. Many patients may also substantially curtail their physical activities and misattribute these adverse lifestyle changes to normal aging or other factors. Bruckel et al. also demonstrated that several patients with CTOs also suffer from undiagnosed major depression, and such patients derived the most benefit from successful CTO PCI.
Patients who undergo successful CTO PCI usually require fewer or no antianginal medications, obviating the medication-related cost and side effects. Eliminating nitrate intake can also allow patients to take phosphodiesterase inhibitors (e.g., sildenafil, vardenafil, tadalafil) for erectile dysfunction, which is common in CAD patients. The Drug-Eluting Stent Implantation Versus Optimal Medical Treatment in Patients With Chronic Total Occlusion (DECISION-CTO) trial (presented at the 2017 American College of Cardiology meeting) randomized 834 patients with coronary CTOs to OMT alone versus OMT + CTO-PCI. Patients in the OMT + CTO PCI group had similar clinical outcomes and quality of life during a median follow-up of 3.1 years. However, the study has several limitations, including early termination before achievement of target enrollment, high cross-over rates (18% in the OMT alone group underwent CTO PCI), revascularization of non-CTO lesions in most patients in both groups, and mild baseline symptoms in both study groups. The EuroCTO (A Randomized Multicentre Trial to Evaluate the Utilization of Revascularization or Optimal Medical Therapy for the Treatment of Chronic Total Coronary Occlusions; NCT01760083) trial (presented at the 2017 EuroPCR meeting) was also stopped early because of slow enrollment after randomizing 407 patients to OMT alone versus OMT + CTO-PCI. Compared with patients randomized to OMT only, patients randomized to CTO PCI had more improvement in angina frequency at 12 months, as assessed by the Seattle Angina Questionnaire.
- 2.
Reduce the need for CABG (and offer revascularization options to patients who are poor candidates for CABG)
In patients with complex stable coronary disease, CABG is the preferred revascularization modality, as it can reduce mortality and the risk of myocardial infarction, whereas outcomes are similar with PCI and CABG in patients with less complex disease (such as those with Syntax score ≤22) ( Fig. 1.3 ). However, many patients decline CABG for nonmedical reasons or because of concerns regarding complications and recovery. Other patients are poor candidates for CABG due to high surgical risk (for example patients with multiple comorbidities or patients who require redo CABG). In such cases CTO PCI provides an attractive alternative treatment option. Examples of patients in whom CTO PCI is preferable over CABG include those with single vessel right or circumflex coronary artery CTO and intractable, medically-refractory angina and those with prior CABG, especially if they have a patent left internal mammary artery graft to the left anterior descending artery ( Fig. 1.3 ).
- 3.
Reduce ischemia
Studies using fractional flow reserve measurement after CTO crossing but before stent implantation showed that myocardial territories supplied by a CTO are ischemic, even when extensive collateral circulation is present. When fractional flow reserve (FFR) was performed in 92 patients immediately after CTO crossing with a microcatheter but before balloon angioplasty and stenting, resting ischemia was observed in 78% of patients and with hyperemia FFR was <0.80 in all patients. Similar findings were observed in a study of 50 CTO patients, all of whom were ischemic regardless of the presence and extent of collateral circulation.
The hemodynamic significance of a lesion in the donor vessel that collateralizes the CTO vessel may change after successful CTO recanalization. In a study by Sachdeva et al., six of nine donor vessels that had baseline ischemia, as assessed by FFR measurement (FFR ≤ 0.80) reverted to nonischemic FFR after successful CTO recanalization. The mean increase in donor vessel FFR after CTO recanalization was 0.098 ± 0.04. In another study the mean increase in donor vessel FFR after CTO recanalization was 0.03. Therefore, evaluation of possible ischemia in a donor vessel supplying collaterals to a CTO territory by FFR should be viewed with caution due to risk of false positive results.
In a study of 301 patients who underwent myocardial perfusion imaging before and after CTO PCI, a baseline ischemic burden of >12.5% was optimal in identifying patients most likely to have a significant decrease in ischemic burden post-CTO PCI. CTO PCI is, therefore, more likely to benefit patients with significant baseline myocardial ischemia.
The presence of a CTO was the strongest independent predictor of incomplete revascularization in the PCI arm of patients treated for multivessel CAD in the SYNTAX trial. Irrespective of surgical or percutaneous revascularization strategy, incomplete revascularization and consequent ischemic burden was associated with significantly higher 4-year clinical event rates including mortality. Successful CTO PCI was relatively low in this cohort compared with current standards.
- 4.
Improve myocardial function
Successful CTO revascularization can improve left ventricular systolic function, provided that the CTO-supplied myocardium is viable and the vessel remains patent during follow-up. In patients with systolic heart failure, CTO revascularization was associated with improvement in left ventricular ejection fraction and improvement in New York Heart Association functional class, angina, and brain natriuretic peptide levels. Three-year follow-up after successful CTO PCI suggested a beneficial effect on left ventricular remodeling, as well as tendency toward improvement in left ventricular ejection fraction.
Note
Viability can be assessed using several techniques. However, if the affected myocardial segment is hypokinetic but not akinetic and if there are no Q-waves in the corresponding region of the electrocardiogram, then viability is highly likely.
In the Evaluating Xience and Left Ventricular Function in Percutaneous Coronary Intervention on Occlusions After ST-Elevation Myocardial Infarction (EXPLORE) trial, patients who underwent primary PCI for ST-segment elevation acute myocardial infarction and were found to have a concomitant CTO in a non–infarct-related artery were randomized to CTO PCI or medical therapy alone within 7 days. Core laboratory adjudicated procedural success was 73%. At 4 months left ventricular ejection fraction and left ventricular end-diastolic volume were similar in the two study groups ( Fig. 1.4 ).
Figure 1.4
Left ventricular function and size at 4-month follow-up in ST-segment elevation acute myocardial infarction patients undergoing chronic total occlusion percutaneous coronary intervention (CTO PCI) versus no CTO PCI. There was no difference in left ventricular ejection fraction or left ventricular end-diastolic volume between the two groups, although a subanalysis suggested improvement in left ventricular function after CTO PCI of the left anterior descending coronary artery.
Reproduced with permission from Henriques JP, Hoebers LP, Ramunddal T, et al. Percutaneous intervention for concurrent chronic total occlusions in patients with STEMI: the EXPLORE trial. J Am Coll Cardiol 2016; 68 :1622–32, Elsevier.
- 5.
Improve long-term survival
Several observational studies and metaanalyses have reported better long-term survival after successful versus failed CTO PCI, even among patients with well-developed collateral circulation. Also in a large registry, patients with a CTO had higher mortality than patients without a CTO. A potential beneficial effect of CTO recanalization on long-term survival may be due to protection from future coronary events in vessels supplying collateral perfusion to the ischemic CTO territory, improved myocardial contractility, and reduction in the risk for ischemic arrhythmias. All studies performed to date are unfortunately limited by their retrospective, observational designs and were not compared with a control group that was only receiving medical therapy. In addition, patients who have unsuccessful CTO PCI are more likely to have complications at the time of their procedure, potentially biasing the results in favor of successful CTO PCI. As described above, the DECISION CTO and EuroCTO trial did not show differences in the incidence of adverse cardiac events during follow-up, but were underpowered and had multiple other limitations.
- 6.
Improve tolerance of future coronary events
Patients with CTO who develop an acute coronary syndrome (ACS) have significantly worse acute and long-term outcomes as compared with those without a CTO, including patients with multivessel CAD ( Fig. 1.5 ) (“double jeopardy”).
