The Long-Term Benefit of CTO Recanalization
Using CTO PCI to improve long-term clinical outcomes.
A 62-year-old man with a history of coronary artery bypass graft surgery 10 years before presentation, an occluded saphenous vein graft to the right coronary artery (RCA), and medically refractory angina was referred for interventional evaluation. He reported that in addition to chronic angina, he had experienced a loss of energy during the previous year; his wife reported that he now spends most of his day at home watching television. Myocardial perfusion imaging showed reversible ischemia in the RCA territory, and the coronary angiogram showed a calcified, tortuous, 50-mm-long chronic total occlusion (CTO) of the RCA. This is the prototypical patient who can benefit from CTO percutaneous coronary intervention (PCI).
THE BENEFIT OF CTO PCI
Historically, barriers to the adoption of CTO PCI, have included technical difficulty and a lack of dedicated expertise, risk of procedural complications, and limited resources. However, at several centers around the world, technical developments have revolutionized CTO PCI in the last decade, offering patients revascularization opportunities that were previously unattainable. Concurrently, there is a growing body of evidence showing that CTO recanalization could provide several benefits, such as symptom improvement (resulting in a decreased need for medications and improved quality of life), improvement in left ventricular systolic function in selected patients with ischemic myocardial dysfunction, possibly improved long-term survival likely related to the achievement of complete revascularization and better tolerance of subsequent ischemic events, reduced arrhythmia burden, and reduced long-term health care costs after the adjustment for quality of life.1,2
Benefit One: Improved Quality of Life
For patients with medically refractory angina due to a CTO, CTO PCI can restore quality of life and reduce or obviate the need for antianginal medications. Meta-analyses have shown that successful versus failed CTO PCI is associated with less residual angina.3,4 Rossello et al studied quality of life and functional status after CTO PCI and found that patients with successful recanalization had improved global physical health, improved mental health, improved exercise tolerance, and smaller ischemic burden.5 Bruckel et al demonstrated that a large proportion of patients with CTOs have undiagnosed major depression, and that these are the patients who benefit the most from successful CTO PCI through the reduction of angina (Figure 1).6 Although quality-of-life measures are sometimes considered “soft endpoints,” they are often the most direct and important benefits to patients. The ongoing EURO-CTO and DECISION-CTO trials are examining the effect of CTO PCI on quality of life, as compared with optimal medical therapy, and will provide novel insights into the outcomes of CTO PCI.
Benefit Two: Improved Myocardial Function
For patients with impaired myocardial contractility due to ischemia, CTO recanalization has the potential to improve myocardial function. Several studies using fractional flow reserve measurement showed that essentially all myocardial territories supplied by a CTO are ischemic, even when extensive collateral circulation is present.7,8 Improvement in left ventricular ejection fraction after CTO recanalization has been demonstrated in patients known to have systolic heart failure, with concomitant improvement in New York Heart Association functional class, angina, and brain natriuretic peptide levels.9 Three-year follow-up after successful CTO PCI suggested a beneficial effect on left ventricular remodeling, as well as a tendency toward improvement in left ventricular ejection fraction.10 Importantly, the improvement of ventricular function depends on the transmural extent of infarction, with no benefit in patients with transmural scarring.
The EXPLORE trial was the first randomized investigation of the effect of CTO PCI on myocardial function after noninfarct-related CTO PCI in the setting of ST-segment elevation myocardial infarction (STEMI).11 Although there was no difference in the ejection fraction in the CTO PCI group as compared with the group without CTO PCI at 4 months (Figure 2), a subanalysis revealed that CTO PCI of the left anterior descending coronary artery was associated with a significant improvement in ejection fraction. Further study is needed to clarify the role of CTO PCI in improving ventricular function in various settings and patients.
Benefit Three: Improved Long-Term Survival and Improved Tolerance of Subsequent Coronary Events
The presence of a CTO has been independently associated with negative long-term outcomes in patients presenting with both STEMI12,13 and non-STEMI.14 The presence of a CTO is the most common reason for incomplete revascularization, which has in turn been associated with a higher risk for subsequent major adverse cardiovascular events.15-18 Moreover, numerous studies19-21 and meta-analyses4,22,23 have reported better long-term survival after successful versus failed CTO PCI (Figure 3). A potential beneficial effect of CTO recanalization on long-term survival could be related to protection from future coronary events in vessels supplying collateral perfusion to the ischemic CTO territory, improved myocardial contractility, and a reduction in the risk for arrhythmias related to ischemia. However, all studies performed to date are limited by their retrospective, observational nature. Randomized data are needed and are eagerly anticipated: the EURO-CTO trial and DECISION-CTO trial will provide a comparison of CTO PCI with medical therapy, with clinical follow-up at 3 and 5 years, respectively.
Benefit Four: Arrhythmia Prevention and Treatment
Another potential benefit of CTO recanalization in selected patients is arrhythmia risk reduction. Nombela-Franco et al showed that in patients who had cardioverter defibrillator implants, the presence of a CTO is associated with the occurrence of ventricular arrhythmias and higher mortality,24 although a subsequent study failed to confirm these findings.25 In patients with refractory arrhythmias due to ischemia, successful CTO recanalization could provide effective treatment (Figure 4).26
Benefit Five: Reduced Long-Term Health Care Costs
The cost of CTO PCI can be significant, given the use of specialized devices and longer mean procedure time as compared with non-CTO PCI.27 However, the potential quality-of-life benefit to severely symptomatic patients is quantifiable. A cost-effectiveness analysis demonstrated that CTO PCI in patients with chronic stable angina resulted in a higher number of quality-adjusted life-years, resulting in a favorable cost-effectiveness ratio as compared with optimal medical therapy.28 Further analysis of the CTO PCI cost-benefit ratio in broader settings will help optimize clinical decision making.
WHEN SHOULD CTO PCI BE PERFORMED?
Although there are limited randomized data on CTO PCI versus medical therapy or surgical revascularization, an expanding body of observational data suggests that CTO PCI can offer important benefits to the patient, with an improved quality of life being the most important. A decision about when to proceed with CTO PCI should take into account not only the potential benefits, but also the likelihood of success (which depends on anatomic characteristics and operator experience) and associated risk (Figure 5). Objective assessment of the success and risk likelihoods can be made using dedicated scores, such as the PROGRESS-CTO and PROGRESS-CTO complications scores, which can be calculated using an online tool found at www.progresscto.org/cto-scores.29,30 Providing each patient with an individualized estimate of potential benefits, risks, and alternatives can greatly facilitate clinical decision making, centered on each patient’s unique circumstances and needs.
After successful recanalization of the RCA CTO using three drug-eluting stents, this patient had a remarkable improvement in energy and quality of life. He is now able to perform all of his daily activities without symptoms and feels like, “He got his life back.” Although such dramatic results will not be achieved in every patient, in the right patient, CTO PCI can be a terrific tool that can improve long-term clinical outcomes.
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Barbara Anna Danek, MD
University of Texas Southwestern Medical Center
VA North Texas Health Care System
Emmanouil S. Brilakis, MD, PhD
Center for Advanced Coronary Interventions
Adjunct Professor of Medicine
University of Texas Southwestern Medical Center
Disclosures: Receives consultant and speaker honoraria from Abbott Vascular, Asahi Intecc Co Ltd., Cordis, a Cardinal Health company, Elsevier, and GE Healthcare; research support from Boston Scientific Corporation, InfraRedx, Inc.; spouse is an employee of Medtronic.