Long-Term Clinical Outcomes after Percutaneous ...

Curr Cardiol Rep (2014) 16:450 DOI 10.1007/s11886-013-0450-7

ISCHEMIC HEART DISEASE (D MUKHERJEE, SECTION EDITOR)

Long-Term Clinical Outcomes after Percutaneous Coronary Intervention for Chronic Total Occlusions Spyretta Golemati & Elias A. Sanidas & George D. Dangas

# Springer Science+Business Media New York 2014

Abstract Optimal treatment of chronic total occlusions (CTOs) remains one of the major challenges in interventional cardiology. A number of factors, including both patient clinical conditions and technical procedural considerations, have been identified to affect percutaneous coronary intervention (PCI) success and long-term outcomes, in large multicenter cohorts as well as smaller patient groups. As opposed to patient-centered factors, technical factors can be managed and as a result, a lot of research aims at improving stent

This article is part of the Topical Collection on Ischemic Heart Disease S. Golemati Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA e-mail: [email protected] E. A. Sanidas : G. D. Dangas Cardiovascular Research Foundation, 111 East 59th street 12th floor, New York, NY 10022, USA E. A. Sanidas e-mail: [email protected] G. D. Dangas Mount Sinai Medical Center, New York, NY, USA G. D. Dangas (*) Cardiovascular Innovation, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY 10029-6574, USA e-mail: [email protected] S. Golemati Department of Biomedical Engineering, Columbia University, New York, NY, USA S. Golemati Ultrasound Elasticity Imaging Laboratory Columbia University Medical Campus, 630 West 168th Street Physicians & Surgeons 19-418, New York, NY 10032, USA

technology and imaging guidance, toward enhancing PCI efficiency, in regards to patient safety. Keywords Chronic total occlusions . CTO . Clinical outcomes . Long-term . Percutaneous coronary intervention . PCI

Introduction Optimal treatment of chronic total occlusions (CTOs), defined as occlusions of duration greater than three months, remains one of the major challenges in interventional cardiology. Decision making for appropriate lesion management consists in selecting between continued medical therapy or revascularization, the latter involving either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). A decision in favor of PCI requires an evidence-based balance between PCI's (a) benefits, namely symptom relief, lower rate of subsequent myocardial infarction (MI) and CABG, and improved long-term survival and (b) drawbacks, including highly complex procedures, low procedural success rates, compared to subtotal stenoses, and high restenosis rates. A number of factors, including both patient clinical conditions and technical procedural considerations, have been identified to affect PCI success and long-term outcomes, mostly in nonrandomized trials [1, 2••, 3, 4]. Based on such evidence, the relevant guidelines state that PCI of a CTO in patients with appropriate clinical indications and suitable anatomy is reasonable when performed by operators with appropriate expertise [1], indicating some uncertainty in optimal selection of CTO patients for PCI, mainly due to the insufficient evidence about the magnitude of benefits of PCI [2••]. This, in combination with the fact that CTOs are detected in approximately 18 % [3] to 30 % [4] of patients referred for diagnostic coronary angiography, suggests that a regular critical review

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of recent evidence is required toward solidifying the relevant guidelines and improving clinical decision making.

Challenges of PCI for CTOs PCI for CTOs is a complex and demanding procedure requiring rigorous training and substantial experience as well as technologically sophisticated equipment and materials [5]. A number of critical steps are incorporated in the PCI procedure, which underline not only the difficult and complex nature of the procedure but also the sources of future trends toward improving the technique and its outcomes [6••]. Guide Wire Crossing Successful passage of the guide wire through the occlusion without injuring the arterial wall is the major challenge in performing a PCI. The retrograde approach has been suggested as an alternative to achieve guide wire passage through the occlusion, but only a few successful cases have so far been reported [7]. Furthermore, local delivery of collagenase into coronary CTOs has been shown to facilitate guide wire crossing [8]. Lesion Complexity Increased length, calcification and tortuosity of the target vessels can significantly complicate the procedure [9, 10]. Stent Options Stent design and technology is a continuously evolving field. The initial use of bare metal stents (BMS) was followed by first-generation drug eluting stents (DES), namely paclitaxel (PES) and sirolimus-eluting (SES) stents, which have been shown to incur fewer incidences of restenosis [11]. Second-generation DES, like everolimus-eluting stents (EES), provide an incremental benefit through better deliverability and further reduction in the risk of reocclusion, and are currently the default choice for PCI of CTOs. Bioabsorbable stents can address one of the major limitations of metallic stents in CTOs, the late acquired malapposition, which is not present post-PCI but only at follow up, due to significant enlargement of the CTO target vessel following successful recanalization [12]. Imaging Guidance Imaging guidance is crucial not only for guiding the wire through the vasculature, but also, and more importantly, for passing the guide wire through the occlusion. The adjunctive use of intravascular ultrasound (IVUS) has been shown to be beneficial in some cases [13], but, overall, it has not proved superior to x-ray angiography [14]. Once a PCI has been completed, procedural, or short-term, success is said to occur when patent flow has been achieved, symptoms have been relieved and the patients do not need to be subsequently referred for CABG. Operator expertise remains critical to success not only because advanced

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techniques, such as the retrograde approach, can be incorporated, but also because shorter times and less contrast can be used, which add to the efficiency of the procedure [5]. Longterm outcomes following a PCI may be determined in terms of symptom relief, reocclusion, yearly mortality and subsequent MI or CABG. The combined effect of the previously mentioned endpoints is mainly expressed through major cardiovascular adverse events (MACE).

Predictors of Outcomes The major factors affecting long-term clinical outcomes of CTO PCI can be divided into three groups: (a) patient and lesion characteristics, including patient age and gender, as well as lesion location (target vessel) and age, (b) preexisting comorbidities, including multivessel disease (MVD), diabetes mellitus (DM), and chronic renal disease (CRD), and (c) technical factors, including stent type and IVUS guidance. Most of these factors affect directly short-term procedural success, which, in turn, is crucial for favorable long-term effects (Table 1). The importance of procedural success in terms of long-term outcomes was also noted in a cohort of 836 CTO subjects, in whom successful PCIs were associated with improved survival up to 5 years [15]. The major findings of recently published studies on the effect of the previously stated factors on long-term clinical outcomes of CTO PCI are summarized in Table 2. Patient and Lesion Characteristics Advancing age of the general population increases the likelihood to detect a CTO on diagnostic coronary angiography. Hoebers et al. reported that 12 % of their investigated patient group of 1791 subjects, in the context of the HORIZONS-AMI trial, was older than 75 years [16]. Procedural success rates were similar for patients older and younger than 75 years but MACE rates were

Table 1 Relation of factors with long-term outcomes of PCI of CTOs Factors

Favorable long-term results

Old age Male gender Target vessel Multi-vessel disease Prior CABG Diabetes mellitus Chronic kidney disease Drug eluting stents IVUS guidance

Negative Positive Unclear Negative Unclear Negative Negative Positive Positive

CABG = coronary artery bypass grafting; IVUS = intravascular ultrasound

Curr Cardiol Rep (2014) 16:450 Table 2 Recent studies showing the different factors affecting CTO PCI long-term clinical outcomes

CABG = coronary artery bypass grafting; CRD = chronic renal disease, DES = drug-eluting stent; DM = diabetes mellitus; IVUS = intravascular ultrasound; MACE = major adverse cardiovascular events; MI: myocardial infarction; MRT = mortality; MVD = multivessel disease, RO = reocclusion; ST = stent thrombosis; TV: target vessel; TVR = target vessel revascularization

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Studies

Factors

Patients

Follow-up

Endpoints

Bataille et al. 2013 [26] Hoebers et al. 2013 [16] Liu et al. 2013 [28] Godino et al. 2013 [25] Murarka et al. 2013 [21]

CRD Age DM MVD RO

1873 1791 153 847 6

30 days, 1 year 5 years 3 years 4 years 6–11 months

MRT MRT, MI, CABG, MACE MACE Cardiac death MACE

Hur et al. 2013 [32] Valenti et al. 2013 [30] de Felice et al. 2013 [24] Claessen et al. 2012 [19] Bataille et al. 2012 [23] Claessen et al. 2012 [4] Claessen et al. 2013 [22] Claessen et al. 2011 [27]

IVUS Stent MVD TV MVD Gender MVD DM

8371 802 551 1734 2020 1791 3283 1742

3 years 6–9 months 1 year 5 years 1 year 5 years 30 days, 3 years 5 years

MRT RO MRT MRT, CABG MRT MRT, MI, CABG, MACE MRT, MACE, ST MRT, MI, CABG

higher in the elderly patients at 5-year follow-up. MACE rates were significantly reduced after successful PCI, compared to MACE rates after failed PCI, in both patient groups. In elderly subjects, this reduction reflected a reduced need for CABG, whereas no differences were noted in terms of mortality and MI. In the same population, consisting of 14 % women, the effect of gender was also investigated on long-term clinical outcomes of CTO PCI [4]. PCI success rates were similar for men and women, and MACE rates were lower after successful, versus failed, PCI in both subject groups. However, procedural success was associated with reduced mortality and need for CABG in men, whereas only a trend toward a reduced need for CABG was observed in women, suggesting a greater benefit of successful PCI to men than to women. History of prior CABG may affect technical success, i.e., successful recanalization, although complication rates may be similar as in those without prior CABG according to the outcomes of a registry of 1363 CTO patients from three US centers [17]. However, long-term effects of prior CABG have not been reported yet. The location of the occlusion within the coronary vasculature may also affect long-term clinical outcomes. In a large cohort of 2608 patients it was shown that PCI for CTO of the left anterior descending (LAD), but not the left circumflex (LCX) or right coronary artery (RCA), was associated with improved long-term survival [18]. However, in a HORIZONS-AMI based population of 1734 patients, it was reported that success rates were similar for PCIs performed in the LAD, LCX, and the RCA. The need for CABG was lower after successful PCI in all three groups, but five-year mortality was significantly reduced after successful PCI in LAD and LCX cases, but not in RCA cases. An interesting finding was that the mortality rate after failed PCI of the RCA was relatively low (4.1 %) compared to that after failed PCI of the LAD (11.0 %) and the LCX (13.9 %) [19].

The age of the occlusion has been generally considered as a predictor of adverse long-term clinical outcomes. The late open-artery hypothesis asserts that the mechanical opening of a persistently occluded infarct-related artery at a time too late for myocardial salvage should improve the long-term outcome. In the randomized OAT study even though high rates of procedural success with PCI and sustained patency were reported there was no clinical benefit during an average 3-year follow-up with respect to death, reinfarction, or heart failure, contrary to the hypothesis [20]. A more recent study, including six subjects with very old CTOs, defined as CTOs older than 20 years, with related ischemia in the corresponding territory has however reported that such CTOs can be effectively revascularized [21]. Preexisting Comorbidities The presence of an occlusion, or even a partial stenosis, in more than one vessel has accounted for unfavorable long-term clinical outcomes in a number of studies. In a cohort of 3283 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI in the HORIZONS-AMI trial, MVD, with or without a CTO, in a non-infarct-related artery (IRA), was an independent predictor of early mortality, namely 0- to 30-day mortality. In the same study, the presence of a CTO in a nonIRA was also an independent predictor of increased late, i.e., 3-year, mortality [22••]. Mortality rates were significantly increased in patients with multiple CTOs compared to those with single CTO or without CTO [23]. Increased mortality rates for increasing disease complexity, i.e., single vessel disease (SVD), MVD without CTO and MVD with CTO, were also reported by de Felice et al. in a group of 551 patients treated with rescue angioplasty. As opposed to the previous study, however, they observed that MVD with CTO, rather than MVD alone, was a predictor of death at 1-year follow-up [24].

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The effect of MVD has also been discussed as a collateral finding, in studies with a different focus. In a study that compared the clinical outcomes in patients not revascularized and in those revascularized with PCI, the presence of threevessel disease was reported as the only significant independent predictor of cardiac death at 4-year follow-up in the revascularized group [25]. In another study focusing on the effect of CRD, MVD was found to be an independent predictor of mortality in patients without CRD, but not in those with CRD. In the investigated 1873 patients undergoing primary PCI for STEMI, Bataille et al. confirmed increasing mortality rates with increasing disease complexity [26]. Diabetes mellitus and CRD are well-known risk factors of cardiovascular disease. In CTO patients with DM, a successful PCI was associated with a reduction in mortality and the need for CABG. Also, compared to non-insulin-dependent DM patients with insulin dependent DM had an increased risk for long-term mortality [27]. DM, as well as DM with renal impairment was demonstrated to be a predictor for MACE in a cohort of 153 CTO patients older than 65 years, successfully treated with PCI, at 3-year follow-up [28]. Chronic renal disease may also affect the clinical outcomes of CTO patients undergoing PCI. In the cohort of Bataille et al. the prevalence of CTO in a non-IRA was twice as great in those with preexisting CRD. The presence of CRD significantly reduced early, i.e., 30-day, and late, i.e., one-year, mortality rates, in the presence of SVD, MVD without CTO and MVD with CTO [26]. Systematic assessment of acute renal failure after PCI for CTO can be performed using the scoring system proposed by Mehran et al. [29]. Technical Factors Evolving generations of stents, from BMS to first generation DES and to second generation DES (EES) have been shown to have favorable effects on long-term clinical outcomes after CTO PCI in a number of studies. The use of DES, rather than BMS, was associated with a reduction in target vessel revascularization (TVR), in patients with and without DM [27, 28]. In a cohort of 802 subjects who underwent successful PCIs clinical and angiographic outcomes were improved for EES compared to DES-treated subjects. Specifically, MACE rates, and even more so target vessel reocclusion rates, were significantly lower in the EES vs. the DES cases, namely 11.6 % vs. 19 %, and 23 % vs. 7 %, respectively [30]. In the same study, the use of the subintimal tracking and reentry (STAR) technique was shown to be associated with an increased reocclusion rate (57 %) and a reduction in the 3-year event-free survival rate. In a recent study, investigating the effect of IVUSguidance, it was shown that IVUS guidance improved clinical outcome in subjects for whom DES were used but not in those in whom BMS were used [31]. Compared to x-ray-guidance, IVUS guidance was recently shown to be associated with reduced 3-year mortality mainly due to its favorable


contribution toward understanding anatomy and guiding stent sizing and placement. However, IVUS guidance was not shown to affect other endpoints, namely risk for MI, TVR, and stent thrombosis [32]. An additional advantage of radiofrequency IVUS is that it allows virtual histology (VH) estimations. Although CTO morphology, in terms of VH, was not found different than non-occlusive lesions the full potential of VH-IVUS has not yet been highlighted [33].

PCI versus Medical Treatment Potential clinical outcomes in patients not treated with PCI are important for making a decision about attempting a PCI. It has been shown that CTO patients who were not revascularized had a significantly higher rate of cardiac mortality and sudden cardiac death compared to those who were revascularized [25]. The superiority of PCI treatment compared to medical therapy, as a result of a failed attempt, was demonstrated in a recently published meta-analysis, in which a total of 12,970 patients were included from 23 observational studies [34••]. A clinical schematic algorithm evaluating stable patient with CTO for potential elective revascularization taking under consideration mainly anatomical variables, ischemia, patient’s history and optimal medical therapy has been recently proposed [2••]. The cost-effectiveness of different treatment options, i.e., PCI versus optimal medical therapy (OMT), is also an important factor for clinical decision making. In this regard, it was recently shown that PCI of CTOs was superior to OMT, in a patient population with severe symptoms [35]. Although CTO-PCI incurred higher costs than OMT it was also associated with greater quality adjusted life years, yielding a significantly higher cost-effectiveness ratio.

Future Trends Several factors have been identified to affect PCI success and subsequent long-term clinical outcomes. Some of these, namely occlusion site, MVD and stent type had been previously identified and their effect was confirmed in the recent literature. Others, namely age, sex, DM and CRD, adjunct pharmacology and IVUS guidance, have recently emerged as potential predictors of favorable long-term outcomes of CTO PCI. Large multi-center trials, including DECISION-CTO (aiming at comparing long-term safety and effectiveness of DES implantation versus optimal medical treatment), and EURO-CTO, are expected to confirm or disprove the effect of the previously mentioned factors, and they may even identify additional ones. The results of such trials, which are currently recruiting, are expected to further enhance decision making in terms of treatment of CTOs.


Among existing and emerging predictors, patient and lesion characteristics, as well as preexisting comorbidities, are rather difficult to manage. Technical factors, on the other hand, including novel stent technology with bioabsorbable scaffolds as well as looking forward imaging with VH-IVUS [33] or even optical coherence tomography (OCT) [36] can be somewhat more easily controlled and might shed some light in the complex mechanisms involved.

Conclusion Several parameters, including patient and lesion characteristics, preexisting comorbidities and technical factors, have been shown to affect long-term clinical outcomes of CTO PCI, making relevant decision making a particularly challenging clinical task. Although factors characterizing patient conditions cannot be easily managed, technical issues can be, and are currently being, thoroughly investigated toward increasing PCI efficiency and patient safety. It is therefore believed that, in the future, decision making in favor of PCI will be presumably easier and more frequent. Compliance with Ethics Guidelines Conflict of Interest Spyretta Golemati declares that she has no conflict of interest. Elias A. Sanidas declares that he has no conflict of interest. George D. Dangas has been a consultant for Abbott Vascular, Boston Scientific, Medtronic; has received grant support from Medicines Co., Abbott Vascular, Eli Lilly; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Sanofi, and Janssen. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

References Papers of particular interest, published recently, have been highlighted as •• Of major importance 1.

Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/ SCAI Guideline for Percutaneous Coronary Intervention: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124:2574–609. 2.•• Tamburino C, Capranzano P, Capodanno D, et al. Percutaneous recanalization of chronic total occlusions: wherein lies the body of proof? Am Heart J. 2013;165:133–42. Systematic literature review proposing a clinical approach algorithm. 3. Fefer P, Knudtson ML, Cheema AN, et al. Current perspectives on coronary chronic total occlusions: the Canadian Multicenter

Page 5 of 6, 450 Chronic Total Occlusions Registry. J Am Coll Cardiol. 2012;59: 991–7. 4. Claessen BE, Chieffo A, Dangas GD, et al. Gender differences in long-term clinical outcomes after percutaneous coronary intervention of chronic total occlusions. J Invasive Cardiol. 2012;24:484–8. 5. Hoye A. Management of chronic total occlusion by percutaneous coronary intervention. Heart. 2012;98:822–8. 6.•• Brilakis ES, Grantham JA, Rinfret S, et al. A percutaneous treatment algorithm for crossing coronary chronic total occlusions. JACC Cardiovasc Interv. 2012;5:367–79. Comprehensive step wised description of the contemporary treatment strategy for CTOs. 7. Uehara Y, Shimizu M, Yoshimura M. A case with successful retrograde stent delivery via AC branch for tortuous right coronary artery. J Invasive Cardiol. 2013;25:E39–41. 8. Strauss BH, Osherov AB, Radhakrishnan S, et al. Collagenase Total Occlusion-1 (CTO-1) trial: a phase I, dose-escalation, safety study. Circulation. 2012;125:522–8. 9. Syrseloudis D, Secco GG, Barrero EA, et al. Increase in J-CTO lesion complexity score explains the disparity between recanalisation success and evolution of chronic total occlusion strategies: insights from a single-centre 10-year experience. Heart. 2013;99:474–9. 10. Grantham JA, Marso SP, Spertus J, House J, Holmes Jr DR, Rutherford BD. Chronic total occlusion angioplasty in the United States. JACC Cardiovasc Interv. 2009;2:479–86. 11. Suttorp MJ, Laarman GJ, Rahel BM, et al. Primary Stenting of Totally Occluded Native Coronary Arteries II (PRISON II): a randomized comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions. Circulation. 2006;114:921–8. 12. Garcia S, Brilakis ES. Optimal stenting strategy for coronary chronic total occlusion interventions: what is next? Catheter Cardiovasc Interv. 2013;81:800–1. 13. Uehara Y, Shimizu M, Yoshimura M. A case of CTO treated with minimum use of contrast media. Catheter Cardiovasc Interv. 2013;82:E884–7. 14. Park KW, Kang SH, Yang HM et al. Impact of intravascular ultrasound guidance in routine percutaneous coronary intervention for conventional lesions: data from the EXCELLENT trial. Int J Cardiol. 2013;167:721–6. 15. Jones DA, Weerackody R, Rathod K, et al. Successful recanalization of chronic total occlusions is associated with improved longterm survival. JACC Cardiovasc Interv. 2012;5:380–8. 16. Hoebers LP, Claessen BE, Dangas GD, et al. Long-term clinical outcomes after percutaneous coronary intervention for chronic total occlusions in elderly patients (>/=75 years): five-year outcomes from a 1,791 patient multi-national registry. Catheter Cardiovasc Interv. 2013;82:85–92. 17. Michael TT, Karmpaliotis D, Brilakis ES et al. Impact of prior coronary artery bypass graft surgery on chronic total occlusion revascularisation: insights from a multicentre US registry. Heart. 2013;99:1515–8. 18. Safley DM, House JA, Marso SP, Grantham JA, Rutherford BD. Improvement in survival following successful percutaneous coronary intervention of coronary chronic total occlusions: variability by target vessel. JACC Cardiovasc Interv. 2008;1:295–302. 19. Claessen BE, Dangas GD, Godino C, et al. Impact of target vessel on long-term survival after percutaneous coronary intervention for chronic total occlusions. Catheter Cardiovasc Interv. 2013;82:76–82. 20. Hochman JS, Lamas GA, Buller CE, et al. Coronary intervention for persistent occlusion after myocardial infarction. N Engl J Med. 2006;355:2395–407. 21. Murarka S, Heuser RR. Chronic total occlusions: successful recanalization of very old lesions. Catheter Cardiovasc Interv. 2013;81: 802–9. 22.•• Claessen BE, Dangas GD, Weisz G, et al. Prognostic impact of a chronic total occlusion in a non-infarct-related artery in patients with

450, Page 6 of 6

23.

24.

25.

26.

27.

28.

29.

ST-segment elevation myocardial infarction: 3-year results from the HORIZONS-AMI trial. Eur Heart J. 2013;33:768–75. Important CTO group related subanalysis from the HORIZONS-AMI trial. Bataille Y, Dery JP, Larose E, et al. Prevalence, predictors and clinical impact of unique and multiple chronic total occlusion in non-infarct-related artery in patients presenting with ST-elevation myocardial infarction. Heart. 2012;98:1732–7. De Felice F, Fiorilli F, Parma A, Musto C, Nazzaro MS, Confessore P, Scappaticci M, Violini R. Effect of multivessel coronary artery disease with or without a concomitant chronic total occlusion on 1year survival in patients treated with rescue angioplasty. J Invasive Cardiol. 2013;25:64–8. Godino C, Bassanelli G, Economou FI, et al. Predictors of cardiac death in patients with coronary chronic total occlusion not revascularized by PCI. Int J Cardiol. 2013. doi:10.1016/j.ijcard. 2012.12.044. Bataille Y, Plourde G, Machaalany J, Abdelaal E, Déry JP, Larose E, Déry U, Noël B, Barbeau G, Roy L, Costerousse O, Bertrand OF. Interaction of chronic total occlusion and chronic kidney disease in patients undergoing primary percutaneous coronary intervention for acute ST-elevation myocardial infarction. Am J Cardiol. 2013;112: 194–9. Claessen BE, Dangas GD, Godino C, et al. Long-term clinical outcomes of percutaneous coronary intervention for chronic total occlusions in patients with versus without diabetes mellitus. Am J Cardiol. 2011;108:924–31. Liu W, Wagatsuma K, Nii H, Toda M, Amano H, Uchida Y. Impact of diabetes on long term follow-up of elderly patients with chronic total occlusion post percutaneous coronary intervention. JGC. 2013;10:16–20. Mehran R, Aymong ED, Nikolsky E, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol. 2004;44:1393–9.

Curr Cardiol Rep (2014) 16:450 30.

31.

32.

33.

34.••

35.

36.

Valenti R, Vergara R, Migliorini A, Parodi G, Carrabba N, Cerisano G, Dovellini EV, Antoniucci D. Predictors of reocclusion after successful drug-eluting stent-supported percutaneous coronary intervention of chronic total occlusion. J Am Coll Cardiol. 2013;61: 545–50. Hur SH, Ako J, Honda Y, Sudhir K, Fitzgerald PJ. Late-acquired incomplete stent apposition: morphologic characterization. Cardiovasc Revasc Med. 2009;10:236–46. Hur SH, Kang SJ, Kim YH, Ahn JM, Park DW, Lee SW, Yun SC, Lee CW, Park SW, Park SJ. Impact of intravascular ultrasoundguided percutaneous coronary intervention on long-term clinical outcomes in a real world population. Catheterization and cardiovascular interventions: official J Soc Card Angiography Interv. 2013;81:407–16. Guo J, Maehara A, Guo N, Ashida K, Chirumamilla A, Shang Y, Pu J, Sanidas E, Moses JW, Leon MB, Weisz G, Stone GW, Mintz GS, Ochiai M. Virtual histology intravascular ultrasound comparison of coronary chronic total occlusions versus non-occlusive lesions. Int J Cardiovasc Imaging. 2013;29:1249–54. Khan MF, Wendel CS, Thai HM, Movahed MR. Effects of percutaneous revascularization of chronic total occlusions on clinical outcomes: a meta-analysis comparing successful versus failed percutaneous intervention for chronic total occlusion. Catheter Cardiovasc Interv. 2013;82:95–107. Large metanalysis showing the superiority of PCI over medical treatment. Gada H, Whitlow PL, Marwick TH. Establishing the costeffectiveness of percutaneous coronary intervention for chronic total occlusion in stable angina: a decision-analytic model. Heart. 2012;98:1790–7. Niccoli G, Ferrante G, Galassi AR, Montone RA, Crea F. Optical coherence tomography follow-up of the subintimal tracking and reentry technique for chronic total occlusion. EuroIntervention. 2010;6:662–3.