Peripheral Artery Disease in Chronic Total Occlusion Percutaneous Coronary Intervention

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J INVASIVE CARDIOL 2024. doi:10.25270/jic/24.00196. Epub August 9, 2024.

Background. The impact of peripheral artery disease (PAD) on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is not well studied.

Methods. We analyzed the association of PAD with CTO-PCI outcomes using data from the PROGRESS-CTO registry of procedures performed at 47 centers between 2012 and 2023.

Results. The prevalence of PAD among 12 961 patients who underwent CTO PCI during the study period was 13.9% (1802). PAD patients were older, more likely to be current smokers, and had higher rates of dyslipidemia, diabetes, cerebrovascular disease, hypertension, prior myocardial infarction, PCI, and coronary artery bypass graft surgery. Their PROGRESS-CTO (1.35 vs 1.22; P < .001) and J-CTO (2.63 vs 2.33; P < .001) scores were higher, lesion length was longer, and angiographic characteristics were more complex. Their access site was more likely to be bifemoral (33.6% vs 30.9%; P = .024) compared with patients with no PAD. Technical (82.9% vs 87.7%; P < .001) and procedural (80.5% vs 86.6%; P < .001) success rates were lower in patients with PAD, while the incidence of major adverse cardiovascular events (MACE) was higher (3.1% vs 1.8%; P < .001), with higher mortality (0.8% vs 0.4%; P = .034), acute myocardial infarction rate (0.9% vs 0.4%; P = .010), and perforations rate (6.6% vs 4.5%; P < .001). In multivariable analysis, PAD was associated with higher MACE (odds ratio [OR]: 1.53; 95% CI, 1.01-2.26; P = .038) and lower technical success (OR: 0.82; 95% CI, 0.69-0.99; P = .039).

Conclusions. PAD patients undergoing CTO PCI have higher comorbidity burden, more complex CTOs, higher MACE, and lower technical success.

Peripheral artery disease (PAD) is common in patients undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO).^1,2 Polyvascular disease, defined as pre-existent atherosclerosis within at least 2 arterial beds (coronary, peripheral, cerebrovascular) has been independently associated with higher rates of major adverse cardiovascular events (MACE),^3-5 while PAD has been associated with increased risk of both death and MACE in patients undergoing PCI.⁶ However, PAD has received limited study in CTO PCI.^7,8  We examined a multicenter registry of CTO PCI to explore the prevalence of PAD and its effects on techniques used during the procedure and in-hospital outcomes.

We reviewed 12 975 CTO PCIs performed at 47 centers (US-based and non-US based) between 2012 and 2023 using data from the PROGRESS-CTO registry. We compared patients with vs without PAD. PAD included claudication (with exertion or at rest); amputation for arterial vascular insufficiency; vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities (excluding dialysis fistulas and vein stripping); aortic aneurysm; positive non-invasive tests; or imaging indicating a stenosis with a diameter of more than 50% in any peripheral artery. Data collection and management were done using REDCap electronic data capture tools hosted at the Minneapolis Heart Institute Foundation.^9,10 Each center’s institutional review board approved the study. Consent was waived by the institutional review board of each center.

The definition of coronary CTOs included coronary lesions with a Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow for at least 3 months, with the duration estimated clinically based on the first onset of angina, prior history of myocardial infarction (MI) in the target vessel territory, or comparison with a prior angiogram.

Calcification was classified angiographically as mild if only spots, moderate if involving less than or equal to 50% of the lesion diameter, and severe if more than 50% of the lesion diameter. The MI definition used was the one described by the Third Universal Definition of Myocardial Infarction (type 4a MI).¹¹ Successful CTO revascularization with a less than 30% residual diameter stenosis in the segment that was treated with restoration of TIMI grade 3 antegrade flow was defined as technical success. Procedural success was defined as achievement of technical success without in-hospital MACE, which included recurrent symptoms requiring urgent repeat target-vessel revascularization with PCI or coronary artery bypass graft (CABG) surgery, MI, death, tamponade requiring either pericardiocentesis or surgery, and stroke. The scores were calculated as previously described.^12-15

The Pearson’s chi-square test was used to compare categorical variables that were reported as counts (percentages). For continuous variables, data were reported as mean ± standard deviation or median (interquartile range). Comparisons of normally distributed variables were made using the independent-samples t-test, and for non-parametric variables using the Mann-Whitney U test. The impact of PAD on the outcomes (technical success and in-hospital MACE) was analyzed using both univariable and multivariable logistic regression, including variables showing significant univariable association in the models (P < .10). Statistical analyses were carried out using R Statistical Software, version 4.2.2 (R Foundation for Statistical Computing). Statistical significance was defined as a P-value of less than 0.05.

Throughout the duration of the study, 1802 out of 12 961 patients (13.9%) who underwent CTO PCI had PAD (Figure 1). PAD patients were older, more likely to be current smokers, less often men, and had a higher prevalence of comorbidities such as diabetes, cerebrovascular disease, hypertension, dyslipidemia, prior heart failure, myocardial infarction, coronary artery bypass graft surgery, and PCI (Table 1).

The angiographic characteristics of the lesions that were studied are presented at Table 2. The right coronary artery was more likely to be the target CTO vessel in patients with PAD (56.5% vs 52.1%; P < .001). The CTOs of PAD patients had a longer length and higher prevalence of proximal cap ambiguity (40.7% vs 33.8%; P < .001), blunt/no stump (57.5% vs 51.8%; P < .001), moderate to severe calcification (55.7% vs 43.6%; P < .001), proximal tortuosity (33.3% vs 27.8%; P < .001), and in-stent restenosis (18.3% vs 15.5%; P = .004). The lesions of PAD patients had higher J-CTO (2.63±1.20 vs. 2.33 ± 1.28; P < .001), PROGRESS-CTO (1.35 ± 1.01 vs 1.22 ± 1.00; P < .001), and PROGRESS-CTO complication scores.

Table 3 presents the procedural techniques. The initial crossing strategy was less likely to be antegrade in PAD cases (79.7% vs 84.8%; P < .001), while primary antegrade dissection and reentry (ADR) (4.2% vs 3.5%; P < .001) and primary retrograde crossing (16.1% vs 11.6%; P < .001) were more common. The retrograde approach (37.0% vs 29.3%; P < .001) and ADR (22.5% vs 20.1%; P = .019) were more commonly used in PAD patients. Procedure (125 vs 110 min; P < .001) and fluoroscopy (47 vs 41 min; P < .001) times were longer in PAD cases.  Balloon uncrossable (12.5% vs 9.2%; P < .001) and undilatable (10.0% vs 7.0%; P < .001) CTO lesions were more common in PAD cases. Intravascular ultrasound (IVUS) use was higher in PAD patients (53.2% vs 47.9%; P < .001). Bifemoral access was more likely in PAD patients (33.6% vs 30.9%; P = .024) compared with patients with no PAD, while biradial access was less common (9.0% vs 11.8%; P = .001).

PAD patients had lower both technical (82.9% vs 87.7%; P < .001) and procedural (80.5% vs 86.6%; P < .001) success, while the MACE rate was higher (3.1% vs 1.8%; P < .001) (Table 4). Acute MI (0.9% vs 0.4%; P = .010), death (0.8% vs 0.4%; P = .034) and perforation (6.6% vs 4.5%; P < .001) were higher in PAD cases. In multivariable analysis, PAD was associated with reduced technical success (odds ratio [OR]: 0.82; 95% CI, 0.69-0.99; P = .039) and increased MACE (OR: 1.53; 95% CI, 1.01-2.26; P = .038) (Figure 2).

The major findings of our study are that (a) the prevalence of PAD in a large CTO PCI registry was 13.9% and, compared with patients without PAD, PAD patients undergoing CTO PCI had (b) higher comorbidity burden, (c) more complex lesions, (d) lower technical and procedural success, and (e) higher MACE.

The prevalence of PAD was 13.9% in our registry, which is similar to other reports. The prevalence of PAD was 17.5% in the Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures (OPEN-CTO) registry,¹⁶ 8.9% to 9.7% in the European Registry of Chronic Total Occlusion (ERCTO) between 2008 and 2015,¹⁷ and 15.9% in a recent study from the National Cardiovascular Data Registry (NCDR) CathPCI Registry² in a sample of 29 407 patients undergoing CTO PCI.

As observed in our study, PAD is associated with high comorbidity burden in patients undergoing CTO PCI.^6,18-20 CTO lesions in PAD patients were more complex, with higher J-CTO and PROGRESS-CTO scores, likely because PAD shares common pathophysiology with coronary artery disease (CAD) resulting in more advanced atherosclerosis in CTO patients who already have PAD.²¹ In a study of 33 880 patients undergoing PCI, patients with PAD were more likely to have moderate to severe calcification (26.8% vs 17.8%; P < .0001), bifurcation lesions (14.5% vs 12.3%; P < .01), any ostial lesion (10.4% vs 7.0%; P < .0001), and also had more lesions (2.2 ± 1.2 vs 1.9 ± 1.1; P < .0001).¹⁸

Femoral access was used more often and radial access less often in PAD patients, likely because of higher lesion complexity.^18,22 In a study of 16 330 acute coronary syndrome (ACS) patients treated with PCI, PAD was a more common comorbidity in both women (3.9% vs 2.6%; P = .03) and men (4.0% vs 2.3%; P < .001) with femoral access site compared with radial access site.²³

Higher lesion complexity also likely explains the higher usage of the retrograde approach and ADR in PAD patients, as well as the lower technical success and higher MACE. In an analysis from the NCDR that included 22 365 CTO PCIs, patients with a failed CTO PCI were more likely to have PAD (16%) compared with patients who had a successful CTO PCI (13%) (P < .001).⁸ In multivariable analysis, PAD was associated with a lower likelihood of CTO-PCI success and with a trend for higher MACE.

Limitations

This research has some limitations. Primarily, the PROGRESS-CTO registry’s observational nature introduces inherent biases. Clinical events were not independently adjudicated, and angiograms were not assessed by a core laboratory. Experienced CTO-PCI operators performed the procedures reported in the registry, which may limit the applicability of the results in settings with less experienced operators. Detailed information of the nature and management of PAD in our cohort was not available.

Individuals with PAD undergoing CTO PCI had a greater burden of comorbidities, higher CTO lesion complexity, worse outcomes, reduced rates of technical and procedural success, and higher MACE compared with patients without PAD, even after accounting for potential confounders.

Michaella Alexandrou, MD¹; Athanasios Rempakos, MD¹; Deniz Mutlu, MD¹; Ahmed Al Ogaili, MD¹; Pedro E. P. Carvalho, MD¹; Dimitrios Strepkos, MD¹; James W. Choi, MD²; Paul Poommipanit, MD³; Khaldoon Alaswad, MD⁴; Mir Babar Basir, DO⁴; Rhian Davies, DO, MS⁵; Farouc A. Jaffer, MD, PhD⁶; Phil Dattilo, MD⁷;  Anthony H. Doing, MD⁷; Lorenzo Azzalini, MD, PhD, MSc⁸; Nazif Aygul, MD⁹; Raj H. Chandwaney, MD¹⁰; Brian K. Jefferson, MD¹¹; Sevket Gorgulu, MD¹²; Jaikirshan J. Khatri, MD¹³; Laura D. Young, MD¹³;  Oleg Krestyaninov, MD¹⁴; Dmitrii Khelimskii, MD¹⁴; Jarrod Frizzell, MD¹⁵; Omer Goktekin, MD¹⁶; James D. Flaherty, MD¹⁷; Daniel R. Schimmel, MD, MS¹⁷; Keith H. Benzuly, MD¹⁷; Mahmut Uluganyan, MD¹⁸; Ramazan Ozdemir, MD¹⁸; Yousif Ahmad, BMBS, PhD¹⁹; Bavana V. Rangan, BDS, MPH¹; Olga C. Mastrodemos, BA¹; M. Nicholas Burke, MD¹; Konstantinos Voudris, MD¹; Yader Sandoval, MD¹; Emmanouil S. Brilakis, MD, PhD¹

From the ¹Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA; ²Texas Health Presbyterian Hospital, Dallas, Texas, USA; Baylor Scott & White Heart and Vascular Hospital, Dallas, Texas, USA; ³University Hospitals, Case Western Reserve University, Cleveland, Ohio, USA; ⁴Henry Ford Cardiovascular Division, Detroit, Michigan, USA; ⁵WellSpan York Hospital, York, Pennsylvania, USA; ⁶Massachusetts General Hospital, Boston, Massachusetts, USA; ⁷Medical Center of the Rockies, Loveland, CO, USA; ⁸Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington, USA; ⁹Selcuk University, Konya, Turkey; ¹⁰Oklahoma Heart Institute, Tulsa, Oklahoma, USA; ¹¹Tristar Hospitals, Tennessee, USA; ¹²Biruni University Medical School, Istanbul, Turkey; ¹³Cleveland Clinic, Cleveland, Ohio, USA; ¹⁴Meshalkin Novosibirsk Research Institute, Novosibirsk, Russia; ¹⁵St. Vincent Hospital, Indianapolis, Indiana, USA; ¹⁶Memorial Bahcelievler Hospital, Istanbul, Turkey; ¹⁷Northwestern Memorial Hospital, Chicago, Illinois, USA; ¹⁸Benzialem Vakif University, Istanbul, Turkey; ¹⁹Yale School of Medicine, Yale University, New Haven, Connecticut, USA.

Acknowledgments: The authors are grateful for the philanthropic support of their generous anonymous donors (2), and the philanthropic support of Drs Mary Ann and Donald A Sens; Mr. Raymond Ames and Ms. Barbara Thorndike; Frank J and Eleanor A. Maslowski Charitable Trust; Joseph F and Mary M Fleischhacker Family Foundation; Mrs. Diane and Dr. Cline Hickok; Mrs. Marilyn and Mr. William Ryerse; Mr. Greg and Mrs. Rhoda Olsen; Mrs. Wilma and Mr. Dale Johnson; Mrs. Charlotte and Mr. Jerry Golinvaux Family Fund; the Roehl Family Foundation; and the Joseph Durda Foundation. The generous gifts of these donors to the Minneapolis Heart Institute Foundation’s Science Center for Coronary Artery Disease (CCAD) helped support this research project.

The abstract has previously been published (doi: 10.1016/j.jscai.2024.101728) and presented at the SCAI (Society for Cardiovascular Angiography and Interventions) 2024 Scientific Sessions.

Disclosures: Dr. Choi serves on the Medtronic advisory board. Dr. Poommipanit is a consultant for Asahi Intecc and Abbott Vascular. Dr. Alaswad is a consultant and speaker for Boston Scientific and Teleflex. Dr. Basir is a consultant for Abbott Vascular, Abiomed, Cardiovascular Systems, Inc (CSI), Chiesi, and Zoll. Dr. Davies receives honoraria from Abiomed, Asahi Intec, Boston Sci, Medtronic, Shockwave, and Teleflex; and serves on advisory boards for Abiomed, Avinger, Boston Sci, Medtronic, Rampart, and Shockwave. Dr. Jaffer has done sponsored research for Canon, Siemens, Shockwave, Teleflex, Mercator, and Boston Scientific; has been a consultant for Boston Scientific, Siemens, Magenta Medical, IMDS, Asahi Intecc, Biotronik, Philips, and Intravascular Imaging Inc.; has equity interest in Intravascular Imaging Inc. and DurVena; and has the right to receive royalties through Massachusetts General Hospital licensing arrangements with Terumo, Canon, and Spectrawave. Dr. Khatri has received personal honoraria for proctoring and speaking from Abbott Vascular, Medtronic, Terumo, Shockwave, and Boston Scientific. Dr. Azzalini has received consulting fees from Teleflex, Abiomed, GE Healthcare, Asahi Intecc, Philips, Abbott Vascular, Reflow Medical, and Cardiovascular Systems, Inc. Dr. Burke receives consulting and speaker honoraria from Abbott Vascular and Boston Scientific. Dr. Sandoval receives consulting/speaker honoraria from Abbott Diagnostics, Roche Diagnostics, Zoll, Phillips; is an associate editor for JACC Advances; and holds patent 20210401347. Dr. Brilakis receives consulting/speaker honoraria from Abbott Vascular, the American Heart Association (associate editor, Circulation), Amgen, Asahi Intecc, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), CSI, Elsevier, GE Healthcare, IMDS, Medicure, Medtronic, Siemens, Teleflex, and Terumo; receives research support from Boston Scientific, and GE Healthcare; is the owner or Hippocrates LLC; and is a shareholder in MHI Ventures, Cleerly Health, Stallion Medical. The remaining authors report no financial relationships or conflicts of interest regarding the content herein.

Address for correspondence: Emmanouil S. Brilakis, MD, PhD, Minneapolis Heart Institute, 920 E 28th Street #300, Minneapolis, MN 55407, USA. Email: esbrilakis@gmail.com; @esbrilakis, @CCAD_MHIF, @m1chaella_alex