Mechanical Circulatory Support in Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Multicenter U.S. Registry

Abstract: Objective. To study outcomes with use of percutaneous mechanical circulatory support (MCS) devices in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Methods. We examined characteristics and outcomes of 1598 CTO-PCIs performed from 2012-2017 at 12 high-volume centers. Results. Patient age was 66 ± 10 years; 86% were men. An MCS device was used electively in 69 procedures (4%) and urgently in 22 procedures (1%). The most commonly used elective MCS device was Impella 2.5 or CP (62%). Compared to patients without elective MCS, patients with elective MCS had higher prevalence of prior heart failure (55% vs 29%; P<.001), prior coronary artery bypass graft surgery (49% vs 35%; P=.02), and lower left ventricular ejection fraction (34 ± 14% vs 50 ± 14%; P<.001). MCS patients had a higher prevalence of moderate/severe calcification (88% vs 55%; P<.001) and higher J-CTO scores (3.1 ± 1.2 vs 2.6 ± 1.2; P<.01), and a greater proportion underwent retrograde crossing attempts (55% vs 39%; P<.01). Despite more complex characteristics in MCS patients, technical success rates (88% vs 87%; P=.70) and procedural success rates (83% vs 87%; P=.32) were similar in the two groups. Use of elective MCS was associated with longer procedure and fluoroscopy times, and higher incidences of in-hospital major adverse cardiovascular events (8.7% vs 2.5%; P<.01) and bleeding (7.3% vs 1.0%; P<.001). Conclusion. Elective MCS was used in 4% of patients undergoing CTO-PCI. Despite more complex clinical and angiographic characteristics, elective use of MCS in high-risk patients is associated with similar technical and procedural success rates, but higher risk of complications, compared to cases without elective MCS. 

J INVASIVE CARDIOL 2018;30(3):81-87.

Key words: mechanical circulatory support, chronic total occlusion, percutaneous coronary intervention, complications

Percutaneous coronary intervention (PCI) of coronary chronic total occlusions (CTOs) can be challenging, and can be associated with a higher risk of complications compared with PCI of non-CTO lesions.¹ Hemodynamic collapse can complicate CTO-PCI, especially when the retrograde approach is used, as it can lead to obstruction of collateral flow and donor-vessel thrombosis or injury, leading to global cardiac ischemia.^2,3 Prophylactic use of percutaneous mechanical circulatory support (MCS) devices during high-risk CTO-PCI may reduce the risk of hemodynamic instability and improve patient tolerance of transient ischemia, facilitating attempts for complete revascularization.⁴ However, to date, there are no published data on the use of percutaneous MCS devices in CTO-PCI. We sought to investigate the current use and clinical outcomes associated with percutaneous MCS in CTO-PCI in a multicenter United States registry. 

Methods

We analyzed data from 1598 CTO-PCIs performed in 1598 patients from 2012 to 2017 at 12 high-volume United States centers in the Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO; ClinicalTrials.gov NCT02061436). 

Definitions. Chronic total occlusions were defined as coronary obstructions with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 for at least 3-month duration. Estimation of the occlusion duration was based on the first onset of anginal symptoms, prior history of myocardial infarction in the target-vessel territory, or comparison with a prior angiogram. Technical success was defined as angiographic evidence of <30% residual stenosis with restoration of TIMI 3 antegrade flow in the CTO target vessel. Procedural success was defined as technical success without the incidence of in-hospital major adverse cardiovascular event (MACE), including death, myocardial infarction, recurrent cardiac symptoms requiring repeat target-vessel PCI or coronary artery bypass graft (CABG) surgery, cardiac tamponade requiring pericardiocentesis or surgery, and stroke prior to discharge from hospital. Myocardial infarction was defined according to the Third Universal Definition of Myocardial Infarction (type 4 myocardial infarction).⁵Major bleeding was defined as bleeding causing reduction in hemoglobin >3 g/dL or bleeding requiring transfusion or surgical intervention. Vascular access complications included major bleeding from the access site or other complications requiring surgical intervention. The J-CTO score was calculated as described by Morino et al,⁶ the PROGRESS-CTO score as described by Christopoulos et al,⁷ the CL score as described by Alessandrino et al,⁸ and the PROGRESS-CTO Complications score as described by Danek et al.³

Mechanical circulatory support. In our cohort, percutaneous MCS devices included the following: intraaortic balloon pump (IABP); Impella 2.5, CP, and 5.0 (Abiomed); TandemHeart (CardiacAssist); veno-arterial extracorporeal membrane oxygenator (VA-ECMO), and HeartMate percutaneous heart pump (Abbott Vascular). Patients who received an MCS device prior to the beginning of the CTO-PCI were considered to have elective MCS placement. Those in whom MCS was instituted after the CTO-PCI began were considered to have urgent MCS. Cases with missing data on technical success, procedural success, or the use of MCS were excluded from the analysis. 

Statistical analysis. Continuous data were summarized as mean ± standard deviation for normally distributed data or median and interquartile range for non-normally distributed data, and compared using t-test or Wilcoxon rank-sum test. Categorical data were presented as frequencies or percentages and compared using a Chi-square or Fisher’s exact test, as appropriate. Multivariable regression was used to calculate adjusted odds ratios for the incidence of in-hospital MACE, with adjustment for J-CTO score and PROGRESS-CTO Complications score. Variables that were associated with the MACE on univariable regression with P<.10 were included in the multivariable model. A two-sided P<.05 was considered statistically significant. All statistical analyses were performed using JMP 12.0 (SAS Institute).

Results

Mean patient age was 66 ± 10 years and 86% were men. MCS was used electively in 69 procedures (4%) and after a complication (urgently) in 22 procedures (1%). Elective and urgent MCS device use is shown in Table 1 and Figure 1. All devices (elective and urgent) were placed percutaneously in the cardiac catheterization laboratory, including the Impella 5.0, which was placed via transcaval access. 

As compared with patients without elective MCS, a greater proportion who underwent CTO-PCI with elective MCS presented with acute coronary syndromes (unstable angina, 38% vs 23%; non-ST elevation myocardial infarction, 19% vs 6%; ST-elevation myocardial infarction, 9% vs 1% [P<.001 for all]). Patients who received elective MCS had higher prevalence of prior heart failure (55% vs 29%; P<.001) and prior CABG surgery (49% vs 35%; P=.02), and lower left ventricular ejection fraction (34 ± 14% vs 50 ± 14%; P<.001) (Figure 2). They also tended to have longer occlusion segments (40 ± 26 mm vs 34 ± 26 mm; P=.12), a lower prevalence of adequate distal target vessels (43% vs 64%; P<.001), and a higher prevalence of moderate or severe calcification (88% vs 55%; P<.001). Patients with MCS use had higher J-CTO scores (3.1 ± 1.2 vs 2.6 ± 1.2; P<.01), higher CL scores (4.3 ± 2.0 vs 3.6 ± 1.8; P=.01), and higher PROGRESS-CTO Complications scores (3.7 ± 1.9 vs 3.2 ± 1.9; P=.04), and a trend toward higher PROGRESS-CTO scores (1.6 ± 1.0 vs 1.3 ± 1.0; P=.07). Clinical, angiographic, and procedural characteristics are shown in Tables 2-4. Of note, patients in whom elective MCS was used were more likely to undergo a CTO-PCI procedure that involved the left anterior descending (LAD) coronary artery (35% vs 23%; P=.02).

Cases performed with elective MCS had overall similar technical  success rates (88% vs 87%; P=.70) and procedural success rates (83% vs 87%; P=.32) as compared with cases performed without elective MCS use. The incidence of in-hospital MACE was higher among patients receiving MCS (8.7% vs 2.5%; P<.01), with a trend toward higher mortality (2.9% vs 0.7%; P=.09). Bleeding or access-site complications occurred more frequently among patients who received prophylactic MCS (10% vs 2%; P<.001). After adjustment for J-CTO score and PROGRESS-CTO Complications score, use of elective MCS was associated with a trend toward higher incidence of in-hospital MACE (odds ratio [OR] for MACE in the elective MCS group, 2.51; 95% confidence interval [CI], 0.90-6.00; P=.08). The adjusted OR for vascular access complications or bleeding with elective MCS was 4.34 (95% CI, 1.54-10.3; P<.01). Procedure time (217 min [IQR, 151-265 min] vs 126 min [IQR, 85-187 min]; P<.001) and fluoroscopy time (74 min [IQR, 46-108 min] vs 43 min [IQR, 27-71 min]; P<.001) were longer in the elective MCS group. Procedural outcomes are summarized in Table 4 and Figure 3.

Twenty-two patients who did not undergo elective MCS device implantation prior to the CTO-PCI required urgent MCS during the procedure. MCS device types used urgently are shown in Table 1. As compared with patients who did not receive any MCS (neither elective nor urgent; n = 1507), patients who received urgent MCS tended to have a higher prevalence of prior CABG (55% vs 35%; P=.06) but had similar left ventricular ejection fraction (51% vs 53%; P=.29) (Figure 2). This group of patients also had a lower prevalence of adequate distal target vessels (29% vs 64%; P<.001), higher prevalence of moderate/severe calcification (90% vs 54%; P<.001), higher prevalence of moderate/severe tortuosity (62% vs 36%; P=.01), and longer occluded segments (63 ± 38 mm vs 34 ± 26 mm; P<.01). In addition, they had higher J-CTO scores (3.6 ± 0.9 vs 2.6 ± 1.2; P<.001), higher CL scores (5.2 ± 1.8 vs 3.6 ± 1.8; P<.001), and higher PROGRESS-CTO Complications scores (4.9 ± 1.4 vs 3.2 ± 1.9; P<.001). As expected, patients needing urgent MCS had significantly lower technical success rates (73% vs 89%; P=.02) and procedural success rates (41% vs 87%; P<.001), and a higher incidence of MACE (41% vs 2%; P<.001), including myocardial infarction (14% vs 1%; P<.001), death (18% vs 0%; P<.001), and emergency pericardiocentesis (18% vs 1%; P<.001). The incidence of coronary perforation was ten-fold higher in the urgent MCS group (32% vs 3%; P<.001). The incidence of major bleeding and vascular access-site bleeding stratified by MCS device is shown in Table 5. 

Median procedure time and fluoroscopy time were also higher in the urgent MCS group (243 min [IQR, 197-324 min] vs 124 min [IQR, 85-185 min] and 88 min [IQR, 56-116 min] vs 43 min [IQR, 27-71 min], respectively; P<.001 for both). 

Discussion

Our study provides new insights into the use of MCS during contemporary CTO-PCI at high-volume centers. Elective MCS was used infrequently (in 4% of CTO-PCIs) and was more common in patients with complex clinical characteristics (prior heart failure, prior CABG, and lower left ventricular ejection fraction) and angiographic characteristics necessitating use of advanced crossing techniques. Despite greater technical difficulty and risk, procedural success rates were similar between the two groups, suggesting that elective use of MCS may be beneficial in facilitating CTO-PCI in higher-risk patient groups. However, the use of MCS was associated with a higher risk of bleeding.

The most commonly used MCS device in our cohort was the Impella CP, followed by the Impella 2.5. Both are axial flow pumps approved for short-term hemodynamic support and have the advantage of relative ease of use as compared to other MCS devices, with no requirement for electrocardiographic gating or a perfusionist.⁹ MCS device selection during PCI is dependent on the degree of hemodynamic support required, anatomical factors, comorbidities, device availability, and operator experience.^9,10

Despite hemodynamic support provided by MCS, the incidence of MACE in the elective MCS group was higher. However, after adjustment for J-CTO and PROGRESS-CTO Complications scores, use of elective MCS was not associated with MACE. Thus, the excess MACE in the MCS group may be attributable to clinical, angiographic, and procedural complexity. Even though use of MCS was associated with higher incidence of bleeding and access-site complications, MCS likely facilitated achievement of high technical success, which may lead to improved long-term outcomes.¹¹ The risk for periprocedural myocardial infarction is known to be higher with use of retrograde techniques.^2,12 In the elective MCS group, despite high use of the retrograde approach, the incidence of myocardial infarction was low, possibly due to improved tolerance to transient ischemia during the occlusion of the retrograde collaterals. 

Compared with elective MCS patients, patients who required urgent placement of MCS during the CTO-PCI procedure had significantly less favorable outcomes (41% incidence of MACE and low technical and procedural success rates). These adverse outcomes likely reflect the urgent need for hemodynamic support in the setting of unanticipated procedural complications, such as coronary perforation, slow flow, or donor vessel complications. In selected cases, elective use of MCS prior to the start of CTO-PCI might be protective against major adverse events. However, it remains difficult to predict which patients would benefit most from elective MCS use. 

Current American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for PCI provide a class IIb recommendation for use of elective MCS during high-risk interventions (level of evidence C)¹³ and the 2015 Society for Cardiovascular Angiography and Interventions/American College of Cardiology/Heart Failure Society of America/Society of Thoracic Surgeons Expert Consensus Statement on the Use of Percutaneous Circulatory Support suggests prophylactic use of MCS in high-risk PCI, especially in the setting of left ventricular ejection fraction <20%-30% or a coronary artery supplying a large myocardial territory.⁹ However, there are limited randomized data regarding the use of MCS during PCI, and those available are derived from a broader high-risk population. 

In the PROTECT II (Prospective, Multicenter, Randomized Controlled Trial of the Impella 2.5 System Versus Intra-Aortic Balloon Pump in Patients Undergoing Non-Emergent High-Risk PCI) trial, patients undergoing high-risk PCI with percutaneous hemodynamic support were defined as those undergoing intervention of an unprotected left main coronary artery or last patent coronary artery with left ventricular ejection fraction ≤35% or three-vessel coronary artery disease and left ventricular ejection fraction ≤30%.⁴ In the BCIS-1 (Balloon Pump Assisted Coronary Intervention Study), high-risk PCI was defined similarly, as left ventricular ejection fraction ≤30% and a large territory of myocardium subtended by stenosed vessels.¹⁴ In our cohort, candidates for elective MCS were selected at the operator’s discretion, with features similar to the PROTECT II and BCIS-1 populations (mean left ventricular ejection fraction, 34%). In addition, planned use of the retrograde approach may have led some operators to use MCS in the absence of reduced ejection fraction. Indeed, a higher proportion of patients with MCS had a primary retrograde crossing attempt (30% vs 16%; P<.001) compared to those who did not have elective MCS. Clinical, hemodynamic, and procedural characteristics should be taken into consideration to determine which patient is at increased risk of hemodynamic compromise and could benefit from elective MCS prior to CTO-PCI. 

Operator experience and the potential for complications related to the MCS device are additional considerations in the use of elective MCS in CTO-PCI. The need for large-bore arterial access (13-14 Fr for Impella 2.5/CP and 15-21 Fr for TandemHeart and Impella 5.0) increases the risk for bleeding and access-site complications, as demonstrated in our cohort (five-fold higher in the elective MCS group compared to patients who did not have elective MCS). Transcaval access for the Impella 5.0 and transseptal puncture for the TandemHeart require significant technical expertise and are currently feasible at few centers.¹⁵ Severe peripheral arterial disease may preclude the use of most MCS devices due to increased risk of lower-extremity ischemia. Lastly, availability and cost associated with the use of MCS may limit use in some practice settings. 

Study limitations. Our study is retrospective in design and there was limited availability of follow-up data on outcomes after discharge from the hospital. Detailed analysis comparing different types of MCS in the setting of CTO-PCI is limited by the relatively small numbers of each device type used. In addition, detailed hemodynamic variables, such as systemic blood pressure, periprocedural cardiac output, and left ventricular end-diastolic pressure, were not collected in the registry. The decision to use MCS was at the clinical discretion of each operator. Data were derived from cases performed by expert operators at high-volume centers; conclusions about technical and procedural outcomes may not be broadly generalizable. 

Conclusion

Despite significantly greater clinical and angiographic complexity among patients who received MCS prior to CTO-PCI, elective MCS was associated with similarly high technical and procedural success rates as compared to patients who did not receive elective MCS, at the cost of increased risk for bleeding and vascular access complications. Further investigation is needed to identify those patients undergoing CTO-PCI who are most likely to benefit from elective MCS.

References

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From the ¹VA North Texas Healthcare System/UT Southwestern Medical Center, Dallas, Texas; ²Henry Ford Hospital, Detroit, Michigan; ³Columbia University, New York, New York; ⁴Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; ⁵Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts; ⁶Torrance Memorial Medical Center, Torrance, California; ⁷PeaceHealth St. Joseph Medical Center, Bellingham, Washington; ⁸Piedmont Heart Institute, Atlanta, Georgia; ⁹Medical Center of the Rockies, Loveland, Colorado; ¹⁰VA San Diego Healthcare System and University of California San Diego, San Diego, California; ¹¹Baylor Heart and Vascular Hospital, Dallas, Texas; ¹²University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; ¹³Minneapolis VA Medical Center, Minneapolis, Minnesota; ¹⁴Boston Scientific, Natick, Massachusetts; ¹⁵Rutgers University–New Jersey Medical School, Newark, New Jersey. 

Funding: The Progress CTO registry has received funding from the Abbott Northwestern Hospital Foundation. Study data were collected and managed using REDCap electronic data capture tools hosted at University of Texas Southwestern Medical Center, supported by CTSA NIH Grant UL 1-RR024982.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr O’Neill reports consultant income from Medtronic and Edwards Lifesciences. Dr Karmpaliotis reports speakers’ bureau income from Abbott Vascular, Medtronic, and Boston Scientific. Dr Jaffer reports consultant income from Boston Scientific, Siemens, and Merck; nonfinancial research support from Abbott Vascular; research grant from National Institutes of Health (HLR01-108229). Dr Yeh reports Career Development Award (1K23HL118138) from the National Heart, Lung, and Blood Institute. Dr Wyman reports honoraria/consulting/speaking fees from Boston Scientific, Abbott Vascular, and Asahi Intecc. Dr Lombardi reports equity in Bridgepoint Medical. Dr Kandzari reports research/grant support and consulting honoraria from Boston Scientific and Medtronic. Dr Lembo reports speakers’ bureau income from Medtronic; advisory board for Abbott Vascular and Medtronic. Dr Patel reports speakers’ bureau income from Astra Zeneca. Dr Mahmud reports clinical trial support from Boston Scientific, Corindus, and Gilead; consultant for The Medicines Company; speakers’ bureau income from Medtronic. Dr Kirtane reports institutional research grants from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude Medical, Vascular Dynamics, Glaxo. Dr Parikh reports speakers’ bureau income from Abbott Vascular, Medtronic, CSI, and Boston Scientific; advisory boards for Medtronic, Abbott Vascular, and Philips. Dr Ali reports grant support and consultant fees from St. Jude Medical and InfraReDx. Dr Garcia reports grants funds/personal fees from Edwards Lifesciences; personal fees from Medtronic, Boston Scientific, and Surmodics. Dr Rangan reports research grants from InfraRedX and Spectranetics. Dr Thompson is an employee of Boston Scientific. Dr Banerjee reports research grants 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 consulting/speaker honoraria from Abbott Vascular, Acist, Amgen, Asahi Intecc, CSI, Elsevier, GE Healthcare, Medicure, and Nitiloop; he serves on the Board of Directors for the Cardiovascular Innovations Foundation and the Board of Trustees of the Society of Cardiovascular Angiography and Interventions; spouse is an employee of Medtronic. Dr Alaswad reports consultant income from Boston Scientific, Abbott Vascular, and Terumo. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted November 27, 2017 and accepted December 7, 2017.

Address for correspondence: Khaldoon Alaswad, MD, Henry Ford Hospital, K2- Catheterization Laboratory, 2799 West Grand Boulevard, Detroit, MI 48202. Email: kalaswad@gmail.com

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