Original Contribution

Temporal Trends in Chronic Total Occlusion Percutaneous Coronary Interventions: Insights From the PROGRESS-CTO Registry

Iosif Xenogiannis, MD1; Fotios Gkargkoulas, MD2; Dimitri Karmpaliotis, MD, PhD2; Khaldoon Alaswad, MD3; Farouc A. Jaffer, MD, PhD4; Robert W. Yeh, MD5; Mitul Patel, MD6; Ehtisham Mahmud, MD6; James W. Choi, MD7; M. Nicholas Burke, MD1; Santiago Garcia, MD1; Anthony H. Doing, MD8; Phil Dattilo, MD8; Catalin Toma, MD9; Barry Uretsky, MD10; Oleg Krestyaninov, MD11; Dmitrii Khelimskii, MD11; Jeffrey W. Moses, MD2; Nicholas J. Lembo, MD2; Manish Parikh, MD2; Ajay J. Kirtane, MD2; Ziad A. Ali, MD2; Juan J. Russo, MD2; Emad Hakemi, MD2; Allison B. Hall, MD1; Ilias Nikolakopoulos, MD1; Evangelia Vemmou, MD1; Aris Karatasakis, MD12; Barbara Danek, MD12; Bavana V. Rangan, BDS, MPH13; Shuaib Abdullah, MD13; Subhash Banerjee, MD13; Emmanouil S. Brilakis, MD, PhD1

Iosif Xenogiannis, MD1; Fotios Gkargkoulas, MD2; Dimitri Karmpaliotis, MD, PhD2; Khaldoon Alaswad, MD3; Farouc A. Jaffer, MD, PhD4; Robert W. Yeh, MD5; Mitul Patel, MD6; Ehtisham Mahmud, MD6; James W. Choi, MD7; M. Nicholas Burke, MD1; Santiago Garcia, MD1; Anthony H. Doing, MD8; Phil Dattilo, MD8; Catalin Toma, MD9; Barry Uretsky, MD10; Oleg Krestyaninov, MD11; Dmitrii Khelimskii, MD11; Jeffrey W. Moses, MD2; Nicholas J. Lembo, MD2; Manish Parikh, MD2; Ajay J. Kirtane, MD2; Ziad A. Ali, MD2; Juan J. Russo, MD2; Emad Hakemi, MD2; Allison B. Hall, MD1; Ilias Nikolakopoulos, MD1; Evangelia Vemmou, MD1; Aris Karatasakis, MD12; Barbara Danek, MD12; Bavana V. Rangan, BDS, MPH13; Shuaib Abdullah, MD13; Subhash Banerjee, MD13; Emmanouil S. Brilakis, MD, PhD1

Abstract: Background. Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has significantly evolved in recent years. Methods. We compared the clinical, angiographic, and technical characteristics, as well as procedural outcomes of CTO-PCIs in a multicenter registry between the “early era” (2012-2016) and the “current era” (2017-2019). Results. Current era patients more often had stage III or IV angina compared with early era patients (71% vs 66%, respectively; P=.03) and were less likely to undergo ad hoc CTO-PCI (13% vs 16%, respectively; P=.04). The J-CTO score was slightly lower in the current era patients vs the early era patients (2.3 ± 1.4 vs 2.5 ± 1.3, respectively; P=.04). Use of antegrade wire escalation increased in the current era (92% vs 83% in the early era patients; P<.001) whereas use of retrograde crossing decreased (29% vs 39% in the early era; P<.001) and antegrade/dissection re-entry decreased (23% vs 32% in the early era; P<.001). Technical success rates (85% in the current era vs 86% in the early era; P=.69) and procedural success rates (83% in the current era vs 85% in the early era; P=.15) were similar, whereas the incidence of in-hospital major cardiovascular events decreased in the current era (2% vs 3% in the early era; P=.04). Conclusions. During recent years, ad hoc CTO-PCI decreased along with decreasing use of retrograde crossing and antegrade dissection and re-entry. Technical and procedural success rates remained stable, whereas the incidence of in-hospital MACE decreased.

J INVASIVE CARDIOL 2020;32(4):153-160. Epub 2020 March 20.

Key words: chronic total occlusion, percutaneous coronary intervention, temporal trends


Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has significantly evolved over time with the development of new equipment and techniques. There has also been growing consensus on the indications (symptom improvement) and key technical aspects (dual coronary injection, careful angiographic review, use of a microcatheter to support the guidewire, use of various crossing strategies, and switching strategy in cases of failure to achieve progress), as reflected in a recent global CTO-PCI consensus statement.1

In contrast, temporal changes in techniques and outcomes of CTO-PCI have received limited study. Konstantinidis et al assessed the outcomes of 17,626 CTO-PCIs that took place between 2008 and 2015 in Europe, concluding that procedural success steadily increased despite the increasing complexity of the lesions, whereas in-hospital complication rates remained essentially unchanged.2 Similarly, Jones et al showed that although case complexity increased over time, overall success rates increased concurrently in an observational cohort study of 5496 CTO-PCIs performed between 2005 and 2015 at nine tertiary cardiac centers across London, United Kingdom.3 

The present study investigated temporal trends in CTO-PCI across several centers experienced in CTO-PCI. 

Methods

We divided CTO-PCIs included in PROGRESS-CTO (the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention; NCT02061436) between January 2012 and February 2019 into two time periods: the “early era” (2012-2016) and the “current era” (2017-2019). Only cases from centers that enrolled patients for at least 2 years during both eras were included in the study, resulting in 3661 CTO-PCIs performed in 3594 patients at 12 centers (Figure 1). We compared the clinical, angiographic, technical and procedural characteristics, and outcomes of CTO-PCI between the two time periods. The study was approved by the institutional review board of each center.

Coronary CTOs were defined as coronary lesions with Thrombolysis in Myocardial Infarction (TIMI) grade 0 flow of at least 3-month duration. Estimation of the duration of occlusion was clinical, 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 assessed by angiography as mild (spots), moderate (involving ≤50% of the reference lesion diameter), or severe (involving >50% of the reference lesion diameter). Moderate proximal vessel tortuosity was defined as the presence of at least 2 bends >70° or 1 bend >90° and severe tortuosity as 2 bends >90° or 1 bend >120° in the CTO vessel. Proximal cap ambiguity was defined as the inability to determine the exact location of the proximal cap of the occlusion due to the presence of obscuring side branches or overlapping branches that could not be resolved despite multiple angiographic projections or by flush ostial occlusion. Interventional collaterals were defined as collaterals considered amenable to crossing by a guidewire and a microcatheter by the operator. A procedure was defined as retrograde if an attempt was made to cross the lesion through a collateral vessel or bypass graft supplying the target vessel distal to the lesion. Antegrade dissection/re-entry (ADR) was defined as antegrade PCI during which a guidewire was intentionally introduced into the subintimal space proximal to the lesion, or re-entry into the distal true lumen was attempted following intentional or inadvertent subintimal guidewire or device crossing. 

Technical success was defined as CTO revascularization with achievement of <30% residual diameter stenosis within the treated segment and restoration of TIMI grade 3 antegrade flow. Procedural success was defined as the achievement of technical success without any in-hospital major adverse cardiovascular event (MACE). In-hospital MACE included any of the following adverse events prior to hospital discharge: death, MI, recurrent symptoms requiring urgent repeat target-vessel revascularization with PCI or coronary artery bypass grafting (CABG), tamponade requiring either pericardiocentesis or surgery, and stroke. MI was defined using the Third Universal Definition of Myocardial Infarction (type 4 MI).4 The J-CTO score was calculated as described by Morino et al,5 the PROGRESS-CTO score as described by Christopoulos et al,6 and the PROGRESS-CTO Complications score as described by Danek et al.7

Categorical variables are expressed as percentages and were compared using Pearson’s Chi-square test or two-tailed Fisher’s exact test. Continuous variables were presented as mean ± standard deviation or median with interquartile range (IQR) and were compared using t-test or Wilcoxon rank-sum test, as appropriate. All statistical analyses were performed with JMP 14.0 (SAS Institute). A two-sided P-value of .05 was considered statistically significant.

Results

The clinical characteristics of the study patients are outlined in Table 1. Patients included in the current era were on average 1 year younger (64 ± 10 years vs 65 ± 10 years in early era patients; P<.01) and the proportion of men was lower in the current era (83% vs 86% in the early era; P<.01). Current era patients were less likely to have diabetes (37% vs 47%; P<.001), dyslipidemia (77% vs 95%; P<.001), prior PCI (63% vs 68%; P<.01), and prior CABG (28% vs 35%; P<.001), but had higher rates of prior MI (54% vs 46%; P<.001) and heart failure (37% vs 31%; P<.001) compared with early era patients. In addition, current era patients were more likely to have severe (class III or IV) angina (71% vs 66% in early era patients; P=.03) as defined by the Canadian Cardiovascular Society classification and less likely to undergo ad hoc CTO-PCI than early era patients (13% vs 16%, respectively; P=.04). 

Table 2 shows the angiographic characteristics of the target CTO lesions. The right coronary artery was the most common target vessel (54% for both eras), while non-CTO PCI was performed more often during the early era (27% vs 31%, P=.02). Current era CTO lesions were shorter (25 [IQR, 15-40 mm] vs 30 mm [IQR, 17-40 mm]; P<.001), less often had moderate or severe calcification (48% vs 56%, P<.001) and moderate or severe tortuosity (33% vs 39%, P<.001), and had lower J-CTO scores (2.3 ± 1.4 vs 2.5 ± 1.3; P=.04) and PROGRESS Complications score (2.8 ± 1.9 vs 3.2 ± 1.9; P<.001) than early era CTO lesions, but not lower PROGRESS-CTO scores (1.1 ± 1.0 for both eras). 

The CTO-PCI techniques and outcomes are described in Table 3. Dual injection was less common during the current era (60% vs 70% in the early era; P<.001) while there was an increase in the use of radial access in the current era (58% vs 36% in the early era; P<.001). In recent years, antegrade wire escalation (AWE) was used more often (92% vs 83% in the early era; P<.001) whereas use of the retrograde approach (29% in the current era vs 39% in the early era; P<.001) and ADR (23% in the current era vs 32% in the early era; P<.001) declined. AWE was more often the successful crossing technique during the current era (54% vs 45% in the early era; P<.001). There was no difference between the two eras in intravascular ultrasound use (39% in the current era vs 42% in the early era; P=.09). The guidewires and microcatheters used for AWE are illustrated in Figures 2A and 2B, respectively. The guidewires and microcatheters used for retrograde crossing are illustrated in Figures 3A and 3B, respectively. Adjunctive devices for lesion preparation were used rarely in both time periods (Figure 4). 

Procedural outcomes are summarized in Table 4. Technical success (85% in the current era vs 86% in the early era; P=.69) and procedural success (83% in the current era vs 85% in the early era; P=.15) remained stable, whereas in-hospital MACE (2% in the current era vs 3% in the early era; P=.04) and in-hospital mortality (0.2% in the current era vs 0.7% in the early era; P=.04) decreased (Figure 5). 

Procedure time (105 min [IQR, 67-164 min] vs 136 min [IQR, 91-203 min]; P<.001), contrast volume (225 mL [IQR, 164-300 mL] vs 280 mL [IQR, 200-370 mL]; P<.001), and air kerma radiation dose (2.38 Gy [IQR, 1.29-4.10 Gy] vs 2.83 Gy [IQR, 1.68-4.523 Gy]; P<.001) also decreased significantly in the current era vs the early era. 

Discussion

The major findings of our study are that as compared with the early era (2012-2016), during the current era (2017-2019): (1) CTO lesion and patient complexity slightly decreased; (2) use of AWE increased, whereas use of retrograde crossing and ADR decreased; (3) technical and procedural success remained stable, whereas; (4) in-hospital MACE decreased. 

The EuroCTO trial demonstrated that CTO-PCI improves angina compared with medical therapy.8,9 During recent years, the proportion of patients with severe angina (class III or IV by the Canadian Cardiovascular Society) who underwent CTO-PCI increased, suggesting selection of more symptomatic patients who are likely to derive more benefit from the intervention.  According to a recent manuscript by CTO-PCI experts from all over the world, ad hoc PCI is discouraged to allow the interventionalist and the cardiac catheterization lab staff enough time to review the angiogram in detail, create a plan, and discuss the potential benefits and risks of the procedure with the patients and their families.1 The recent decrease in the frequency of ad hoc PCIs is, therefore, a step in the right direction.

In contrast to a recent publication2 from the EuroCTO club that reported an increase in J-CTO score from 1.76 ± 1.03 in 2008 to 2.17 ± 0.91 in 2015, the J-CTO scores in our study were slightly higher during the early era compared with the current era (2.5 ± 1.3 vs 2.3 ± 1.4, respectively). However, J-CTO scores were high in both eras. Also, in a EuroCTO longitudinal study, the J-CTO scores during 2010-2011 and 2012-2013 were higher than in 2014-2015 (2.14 ± 0.98 vs 2.24 ± 0.93 vs 2.10 ± 0.97, respectively; P<.001). Finally, data from the two studies were derived from different time periods (2008-2015 for the EuroCTO club study and 2012-2019 for the PROGRESS-CTO registry). 

Although dual coronary injection is strongly recommended to better understand the coronary anatomy and improve success and safety, it was performed less often during the current era in the present study. This could potentially be explained by increased frequency of AWE use and decrease in use of the retrograde approach, or attempts to reduce the amount of contrast. However, dual injection should be utilized for almost every CTO-PCI, with the exception of cases where well-defined ipsilateral collaterals are present. As recently reported by the PROGRESS-CTO registry, use of radial access significantly increased in recent years and was associated with similar technical and procedural success rates, as well as similar in-hospital MACE rates, but with fewer major bleedings when only the radial artery access was utilized.10 

In contrast to the report by the EuroCTO club, our study showed that use of retrograde and ADR declined while use of AWE increased in recent years, which may in part explain the decrease in complications, as more complex crossing techniques have been associated with higher risk of complications.11-14 Nevertheless, the retrograde approach and ADR remain critically important for achieving success, especially in more complex CTOs.13,15 The increase in AWE success could be related to improvements in guidewire and microcatheter designs. The rate of intravascular ultrasound use remained relatively stable over time at approximately 40%, which is much higher than the 16.5% rate reported by the EuroCTO club for years 2014-2015, but lower than the 47.5% rate reported by Okamura et al in a Japanese study of CTO-PCIs performed between 2009-2011.2,16

Currently, the technical and procedural success rates for CTO-PCI range between 85%-90%, and MACE rates range between 0.5%-7% at experienced centers around the world.2,12,15,17,18 In our study, there was no change in success rate over time, possibly because those rates were high to begin with (89% during the first year of the registry). However, we observed a significant decline in the incidence of complications during recent years. Moreover, radiation dose and contrast volume are decreasing, demonstrating that CTO-PCI is becoming safer and more efficient. In addition to less frequent use of retrograde crossing, the decreasing use of left ventricular assist devices in addition to the slight decrease in lesion complexity could help explain the decrease in complications.

Study limitations. First, this is an observational retrospective study without long-term follow-up. Second, due to the large number of operators, there is a possibility of reporting bias. Third, there was no core laboratory assessment of the study angiograms or clinical event adjudication. Fourth, the separation of the cases into two separate time frames was arbitrary. Finally, the procedures were performed in dedicated, high-volume CTO centers by experienced operators, limiting the extrapolation to less-experienced operators and lower-volume centers.

Conclusion

During the most recent years, CTO-PCI has been performed in patients with more severe angina. Technical and procedural success rates remain high, whereas in-hospital MACE rate has decreased. With continuous refinements in equipment, techniques, and education, further improvement in clinical outcomes is anticipated. 

Acknowledgments. Study data were collected and managed using Research Electronic Data Capture (REDCap) electronic data capture tools hosted at the Minneapolis Heart Institute Foundation (MHIF), Minneapolis, Minnesota. REDCap is a secure, web-based application designed to support data capture for research studies, providing: (1) an intuitive interface for validated data entry; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for importing data from external sources.


From the 1Minneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota; 2Columbia University, New York, New York; 3Henry Ford Hospital, Detroit, Michigan; 4Massachusetts General Hospital, Boston, Massachusetts; 5Beth Israel Deaconess Medical Center, Boston, Massachusetts; 6VA San Diego Healthcare System and University of California San Diego, La Jolla, California; 7Baylor Heart and Vascular Hospital, Dallas, Texas; 8Medical Center of the Rockies, Loveland, Colorado; 9University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; 10VA Central Arkansas Healthcare System, Little Rock, Arkansas; 11Meshalkin Novosibrisk Research Institute, Novosibirsk, Russia; 12Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey; and 13VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, Texas.

Funding: The Progress CTO registry has received support from the Abbott Northwestern Hospital Foundation, Minneapolis, Minnesota; and the Joseph F. and Mary M. Fleischhacker Foundation.

Disclosures: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Karmpaliotis reports speaker honoraria from Abbott Vascular, Abiomed, and Boston Scientific; equity in Traverse Vascular, Soundbite, and Saranas. Dr Alaswad reports consulting fees from Terumo and Boston Scientific; consultant (non-financial) for Abbott Laboratories. Dr Jaffer reports consultant income from Abbott Vascular, Boston Scientific, and Siemens; research grant support from Canon, Siemens, and the National Institutes of Health. Dr Yeh reports grants and personal fees from Abbott Vascular, Boston Scientific, and Medtronic; career development award (1K23HL118138) from the National Heart, Lung, and Blood Institute. Dr Choi reports advisory board fees from Medtronic. Dr Patel reports speakers’ bureau income from Astra Zeneca. Dr Mahmud reports consulting fees from Abiomed, CSI, Medtronic, and Corindus; equity in Abiomed. Dr Burke reports consulting and speaker honoraria from Abbott Vascular and Boston Scientific. Dr Garcia reports personal fees from Abbott Vascular and Medtronic. Dr Moses reports consultant income from Boston Scientific and Abiomed. Dr Lembo reports personal fees from Abbott Vascular, Abiomed, Boston Scientific, and Medtronic. Dr Parikh reports advisory board/speakers’ bureau income from Boston Scientific; advisory board income from Abbott Vascular and Medtronic; speakers’ bureau income from CSI. Dr Kirtane reports institutional research grants to Columbia University from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude Medical, Vascular Dynamics, Glaxo SmithKline, and Eli Lilly. Dr Ali reports grant support/personal fees from Abbott Vascular and CSI; consultant fees/honoraria/personal fees from Amgen, Astra Zeneca, Abiomed, Boston Scientific, Cardinal Health, Opsens Medical, and Acist Medical; equity in Shockwave Medical. Dr Rangan reports research grant support from InfraReDx and The Spectranetics Corporation. Dr Banerjee reports research grant support from Gilead and The Medicines Company; consultant/speaker honoraria from Covidien and Medtronic; ownership in MDCare Global (spouse); intellectual property in HygeiaTel. Dr Brilakis reports personal fees from Abbott Vascular, CSI, Elsevier, GE Healthcare, Medtronic, Boston Scientific, InfraRedx, Biotronik, Teleflex, American Heart Association (associate editor, Circulation), Cardiovascular Innovations Foundation (Board of Directors); grant support from Siemen and, Regeneron; shareholder in MHI Ventures; Board of Trustees, Society of Cardiovascular Angiography and Interventions. The remaining authors report no conflicts of interest regarding the content herein. 

Manuscript submitted September 20, 2019, provisional acceptance given October 2, 2019, final version accepted October 7, 2019.

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

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