Scandinavian Cardiovascular Journal

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/icdv20

Outcome of hybrid compared to conventional revascularization in multivessel coronary artery disease A matched-group comparison of 3-year outcome following hybrid myocardial revascularization, conventional coronary artery bypass grafting, and percutaneous coronary intervention Ivy Susanne Modrau , Per Hostrup Nielsen , Dorthe Viemose Nielsen , Evald Hoej Christiansen , Torben Hoffmann , Erik Thorlund Parner & Leila Louise Benhassen To cite this article: Ivy Susanne Modrau , Per Hostrup Nielsen , Dorthe Viemose Nielsen , Evald Hoej Christiansen , Torben Hoffmann , Erik Thorlund Parner & Leila Louise Benhassen (2020): Outcome of hybrid compared to conventional revascularization in multivessel coronary artery disease, Scandinavian Cardiovascular Journal, DOI: 10.1080/14017431.2020.1821910 To link to this article: https://doi.org/10.1080/14017431.2020.1821910

View supplementary material

Published online: 30 Sep 2020.

Submit your article to this journal

Article views: 1

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=icdv20

SCANDINAVIAN CARDIOVASCULAR JOURNAL https://doi.org/10.1080/14017431.2020.1821910

ORIGINAL ARTICLE

Outcome of hybrid compared to conventional revascularization in multivessel coronary artery disease A matched-group comparison of 3-year outcome following hybrid myocardial revascularization, conventional coronary artery bypass grafting, and percutaneous coronary intervention Ivy Susanne Modraua,b , Per Hostrup Nielsena, Dorthe Viemose Nielsenc, Evald Hoej Christiansend, Torben Hoffmanna,b, Erik Thorlund Parnere and Leila Louise Benhassena,b a

Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark; bDepartment of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark; cDepartment of Anaesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark; dDepartment of Cardiology, Aarhus University Hospital, Aarhus, Denmark; eDepartment of Public Health, Section for Biostatistics, Aarhus University, Aarhus, Denmark ABSTRACT

Objectives. Evaluation of 3-year clinical outcome of hybrid myocardial revascularization (HMR) compared to conventional revascularization strategies in patients with multivessel coronary artery disease involving the proximal left anterior descending artery. Design. Retrospective matched cohort study based on a prospective feasibility study including 103 elective patients undergoing staged HMR from October 2010 until February 2012. The Western Denmark Heart Registry was used to identify patients who underwent coronary artery bypass grafting (CABG) and multivessel percutaneous coronary intervention (PCI) by matching on number of diseased vessels, age and comorbidity score. Primary endpoint was the composite rate of major adverse cardiovascular and cerebrovascular events (MACCE) at 3-year follow-up. Secondary endpoints included individual MACCE components, acute kidney injury, and cardiovascular readmissions. Results. There was no difference between MACCE in the three groups (HMR 31.1%; CABG 20.4%; PCI 20.4%, p ¼ .11). Estimates of repeat revascularization were significantly increased with HMR versus CABG. In the CABG group, fewest patients required cardiovascular readmissions though with the highest incidence of acute kidney injury. Conclusions. HMR was not superior with respect to MACCE compared with CABG and PCI. It may, however, represent a safe alternative to conventional revascularization treatment considering the specific procedure-associated morbidity.

Introduction Hybrid myocardial revascularization (HMR) is defined as combination of minimally invasive coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with multivessel coronary artery disease (MVD). HMR, using minimally invasive off-pump surgery combined with PCI, proposes to offer “the best of two worlds” for patients with MVD involving the left anterior descending artery (LAD). Several factors reduce the risk of renal and pulmonary complications, bleeding, infection, and neurological adverse events: a small incision, absence of full sternotomy, lack of aortic manipulation, and avoidance of cardiopulmonary bypass with cardioplegic arrest. The concept of HMR has been assessed in numerous small case series and registry studies [1]. Short-term clinical outcome after HMR seems comparable to CABG with reduced morbidity. However, few observational studies have compared HMR to CABG with mid- or long-term follow-up CONTACT Ivy Susanne Modrau [email protected] Jensens, Boulevard 99, Aarhus N, 8200, Denmark Supplemental data for this article can be accessed here. ß 2020 Informa UK Limited, trading as Taylor & Francis Group

ARTICLE HISTORY

Received 27 March 2020 Revised 25 July 2020 Accepted 2 September 2020 KEYWORDS

Coronary artery bypass; coronary artery disease; hybrid myocardial revascularization; percutaneous coronary intervention; treatment outcome

[2,3]. A single randomized controlled feasibility study has compared 100 HMR patients with 100 conventional CABG patients. Recent 5-year follow-up data showed comparable rates of all-cause death, myocardial infarction, stroke, and repeat revascularization [4]. Observational comparative studies may help to evaluate the value of HMR in view of the paucity of randomized trial data. To our knowledge, only one study has performed a direct comparison of HMR to CABG and multivessel PCI with mid-term follow-up [5]. The aim of the present study was to compare 3-year clinical outcome following elective staged HMR with conventional myocardial revascularization in an exact-matched cohort of patients with MVD involving the LAD.

Materials and methods Patient population Our retrospective cohort study is based on prospectively registered data involving adult patients undergoing

Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Palle Juul-

2

I. S. MODRAU ET AL.

myocardial revascularization at our institution. The study followed a pre-specified plan, including pre-specified outcomes, and matching characteristics. All 103 HMR patients were recruited from the prospective cohort study to assess feasibility and safety of elective staged HMR (Clinical Trial Registration: NCT01496664). The study was approved by the Central Denmark Region Committee on Biomedical Research Ethics and conforms to the principles outlined in the Declaration of Helsinki. Written informed consent was obtained from all patients enrolled in the HMR feasibility study, while requirement for individual patient consent was waived for patients in the control groups. HMR-patients were enrolled from October 2010 until February 2012. Procedural feasibility and 1-month safety results, as well as 1-year clinical and angiographic results have been published [6,7]. Inclusion criteria were age 18 years, and MVD involving the LAD. A significant stenosis was defined as >75% by visual assessment or fractional flow reserve 75% reduced Loss: eGFR < 15 ml/min, > 27 days End-stage kidney disease: eGFR < 15ml/min, > 90 days Missing values

CABG

103 77 23 1 0 0 2 0

74.8 22.3 1.0 0.0 0.0 1.9

PCI

103

(65.2–82.8)% (14.7–31.6)% (0.0–5.3)% (0.0–3.5)% (0.0–3.5)% (0.2–6.8)%

65 23 10 4 0 1 0

63.1 22.3 9.7 3.9 0.0 1.0

(53.0–72.4)% (14.7–31.6)% (4.8–17.1)% (1.1–9.6)% (0.0–3.5)% (0.0–5.3)%

103 41 2 0 0 0 1 59

93.2 4.5 0.0 0.0 0.0 2.3

(81.3–98.6)% (0.6–15.5)% (0.0–8.0)% (0.0–8.0)% (0.0–8.0)% (0.1–12.0)%

Classification of acute kidney injury according to the RIFLE criteria [12]. Data presented as number and mean (CI ¼ confidence interval). CABG: coronary artery bypass; eGFR: estimated glomerular filtration rate (mL/min/1.73 m2); HMR: hybrid myocardial revascularization; PCI: percutaneous coronary intervention. One patient with pre-existing end-stage renal disease.

PCI group). In contrast, the mean length of readmissions was highest in the CABG-group (mean 10.3 days, CI: 2.6–18.1), as compared to the HMR group (3.1 days, CI: 2.0–4.1, p ¼ .007), and the PCI group (4.1 days, CI: 2.6–5.5, p ¼ .05).

Discussion This study set out to compare mid-term clinical outcome following elective HMR with the conventional revascularization strategies of CABG and multivessel PCI. Our findings indicate no significant difference in the cumulative MACCE rates between the groups at 3-year follow-up. Our results following conventional revascularization were in accordance with 3-year follow-up data from the SYNTAX trial [11]. Composite MACCE rates in the subgroup of patients with three-vessel disease and low SYNTAX-score (0–22) were 22.2% after CABG, and 25.8% after PCI, respectively (p ¼ .45). We found a significantly higher SYNTAX-score suggesting higher lesion complexity in the HMR-group and CABGgroup compared to the PCI-group, which could potentially result in favorable outcome in the PCI-group. The rates of the individual MACCE components were comparable with exception of a higher repeat revascularization rate in the HMR-group. The repeat revascularization rate following HMR in our study was higher than reported in other observational studies with comparable cardiovascular pathology [2,12]. The majority of these repeat revascularizations during the first year were driven by angiographic findings without associated symptoms of ischemia. We did not observe a “catch-up” phenomenon of repeat revascularization in the CABG- and PCI-group throughout the following 2 years of observation. As expected, the requirement of blood transfusion decreased across categories of decreasing invasiveness of the three revascularization strategies. The observed rate of reoperation for hemorrhage of 6.8% in both surgical groups was three times higher than the rates reported in a large registry study based on the Society of Thoracic Surgeons National Cardiac Database [13]. This finding may be linked to a lowered threshold for reoperation in line with the growing evidence of the adverse effects of blood transfusions. The observed incidence of acute kidney injury is in accordance with other studies on CABG patients [14,15].

Evaluation of renal function following HMR in clinical studies is often limited to the incidence of postoperative renal failure [2,16]. However, several studies have confirmed even discrete impairment of renal function following cardiac surgery to be associated with adverse long-term outcomes like incident or progression of chronic kidney disease, myocardial infarction, heart failure, stroke and all-cause mortality [17,18]. Few studies have compared incidence and length of stay of cardiac readmissions following different modalities of revascularization in a long-term perspective. In our study, significantly fewer patients required readmissions due to cardiac causes following CABG, though with the longest total length of stay as compared to the HMR and PCI. This finding might reflect the lower repeat revascularization rate following CABG compared to PCI. The strengths of the present study are the accurate registry data that allowed detailed matching of controls to HMR patients, and the complete three-year follow up on all but one outcome measures. Limitations The main limitation of the present study is its retrospective observational nature and the small number of patients. This study was not sufficiently powered to draw any firm conclusion regarding the MACCE endpoints. Our results need to be assessed in context with other studies in order to build up much needed evidence on the topic. The SYNTAX-calculation was performed retrospectively and therefore did not represent a matching criterion for the control patients receiving PCI or CABG. The high repeat revascularization rate in the HMR group was primarily driven by angiography due to the protocol and not symptoms. This represents a bias against HMR, as this protocol was not implemented in the CABG- and PCI groups.

Conclusion In conclusion, our findings suggest non-superior 3-year clinical outcome after HMR as compared to conventional myocardial revascularization. Consideration of the procedure-associated morbidity may assist the heart team to tailor individualized revascularization strategy.

6

I. S. MODRAU ET AL.

Acknowledgments The authors thank research secretary Helle Bargsteen for her invaluable support. The authors thank members of the Hybrid Coronary Revascularization Study Group at Aarhus University Hospital: Vibeke E. Hjortdal, Michael Maeng, Christian J. Terkelsen, Steen D. Kristensen, Hans E. Bøtker, Anne K. Kaltoft, Lars R. Krusell, Jens F. Lassen, Henning S. Kelbaek, Lone K. Andersen, and Leif Thuesen.

[11]

[12]

Disclosure statement No potential conflict of interest was reported by the author(s).

[13]

Funding This work was supported by grants from the Obel Family Foundation, and the Foundation for Health Research in Central Region Denmark.

[14]

[15]

ORCID Ivy Susanne Modrau

https://orcid.org/0000-0002-2812-6591

References [1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

Verhaegh AJFP, Accord RE, van Garsse L, et al. Hybrid coronary revascularization as a safe, feasible, and viable alternative to conventional coronary artery bypass grafting: what is the current evidence? Minim Invasive Surg. 2013;2013:142616. Harskamp RE, Bagai A, Halkos ME, et al. Clinical outcomes after hybrid coronary revascularization versus coronary artery bypass surgery: a meta-analysis of 1,190 patients. Am Heart J. 2014;167:585–592. Sardar P, Kundu A, Bischoff M Chatterjee S, et al. Hybrid coronary revascularization versus coronary artery bypass grafting in patients with multivessel coronary artery disease: a metaanalysis. Catheter Cardiovasc Interv. 2018;91:203–212. Tajstra M, Hrapkowicz T, Hawranek M, et al.; POL-MIDES Study Investigators. Hybrid coronary revascularization in selected patients with multivessel disease: 5-year clinical outcomes of the prospective randomized pilot study. JACC Cardiovasc Interv. 2018;11:847–852. Shen L, Hu S, Wang H, et al. One-stop hybrid coronary revascularization versus coronary artery bypass grafting and percutaneous coronary intervention for the treatment of multivessel coronary artery disease: 3-year follow-up results from a single institution. J Am Coll Cardiol. 2013;61:2525–2533. Modrau IS, Nielsen PH, Bøtker HE, et al. Feasibility and early safety of hybrid coronary revascularisation combining off-pump coronary surgery through J-hemisternotomy with percutaneous coronary intervention. EuroIntervention. 2015;10:e1–e6. Modrau IS, Holm NR, Maeng M, et al.; Hybrid Coronary Revascularization Study Group. One-year clinical and angiographic results of hybrid coronary revascularization. J Thorac Cardiovasc Surg. 2015;150:1181–1186. Modrau IS, Nielsen DV, Nielsen PH. Off-pump anastomosis of the left internal mammary artery to the left anterior descending coronary artery through a left inferior J-hemisternotomy. Multimed Man Cardiothorac Surg. 2017. Ancona GD, Karamanoukian HL, Ricci M, et al. Graft revision after transit time flow measurement in off-pump coronary artery bypass grafting. Eur J of Cardio-Thorac Surg. 2000;17: 287–293. The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS), European Association for Percutaneous Cardiovascular Interventions

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

(EAPCI), et al. Guidelines on myocardial revascularization. Eur J Cardiothorac Surg. 2010;38(Suppl):1–52. Head SJ, Holmes DJ Jr, Mack MJ, et al.; SYNTAX Investigators. Risk profile and 3-year outcomes from the SYNTAX percutaneous coronary intervention and coronary artery bypass grafting nested registries. JACC Cardiovasc Interv. 2012;5:618–625. Puskas JD, Halkos ME, DeRose JJ, et al. Hybrid coronary revascularization for the treatment of multivessel coronary artery disease: a multicenter observational study. J Am Coll Cardiol. 2016;68:356–365. Mehta RH, Sheng S, O’Brien SM, et al.; Society of Thoracic Surgeons National Cardiac Surgery Database Investigators. Reoperation for bleeding in patients undergoing coronary artery bypass surgery: incidence, risk factors, time trends, and outcomes. Circ Cardiovasc Qual Outcomes. 2009;2:583–590. Ryden L, Ahnve S, Bell M, et al. Acute kidney injury following coronary artery bypass grafting: early mortality and postoperative complications. Scand Cardiovasc J. 2012;46:114–120. Liotta M, Olsson D, Sartipy U, et al. Minimal changes in postoperative creatinine values and early and late mortality and cardiovascular events after coronary artery bypass grafting. Am J Cardiol. 2014;113:70–75. Rosenblum JM, Harskamp RE, Hoedemaker N, et al. Hybrid coronary revascularization versus coronary artery bypass surgery with bilateral or single internal mammary artery grafts. J Thorac Cardiovasc Surg. 2016;151:1090–1091. Ishani A, Nelson D, Clothier B, et al. The magnitude of acute serum creatinine increase after cardiac surgery and the risk of chronic kidney disease, progression of kidney disease, and death. Arch Intern Med. 2011;171:226. Hansen MK, Gammelager H, Jacobsen CJ, et al. Acute kidney injury and long-term risk of cardiovascular events after cardiac surgery: a population-based cohort study. J Cardiothorac Vasc Anesth. 2015;29:617–625. Thygesen K, Alpert JS, Jaffe AS, ESC Committee for Practice Guidelines (CPG), et al. Third universal definition of myocardial infarction. Eur Heart J. 2012;33:2551–2567. Moussa ID, Klein LW, Shah B, et al. Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the society for cardiovascular angiography and interventions (SCAI). J Am Coll Cardiol. 2013;62:1563–1570. Bellomo R, Ronco C, Kellum JA, et al.; Acute Dialysis Quality Initiative Workgroup. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204–12. Levey AS, Stevens LA, Schmid CH, et al.; for the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612. Rasmussen LA, Bøtker HE, Jensen LO, et al. Quality assurance of the Western Denmark heart registry, a population-based healthcare register. Dan Med J. 2017;64:1–7.

Appendix Video legend: Outcome of hybrid compared to conventional myocardial revascularization in multivessel coronary artery disease. Main study results outlined by the author.

Definition of outcome measures Spontaneous myocardial infarction was defined according to the third universal definition of myocardial infarction [19]. Post-procedural myocardial infarction was defined according to the Society for

SCANDINAVIAN CARDIOVASCULAR JOURNAL

Cardiovascular Angiography and Intervention [20]. Stroke was defined as acute episode of neurological dysfunction persisting for more than 24 h. Any revascularization procedure up to 3 years following the index procedure was defined as repeat revascularization. Deep sternal wound infection was defined as re-exploration due to mediastinitis within 90 days after the initial surgical procedure. Incidence and severity of acute kidney injury was assessed according to the RIFLE criteria [21]. Here, we calculated eGFR according to the CKD EPI Equation for Estimating GFR [22]. Baseline kidney function was estimated based on maximum plasma creatinine during a 4-week period prior to intervention. Diagnosis and classification of acute kidney injury was based on change of maximum plasma creatinine values from baseline up to seven days after intervention. Finally, we recorded total length of stay of index hospitalization, number and total length of stay of any

7

readmission due to cardiovascular causes during follow-up, and requirement of blood transfusion up to 1-month follow-up.

Data sources WDHR is a semi-national web-based mandatory registry including comprehensive clinical records of all invasive cardiac interventions performed in adult patients. The database is valued for its high completeness and accuracy [23]. The NPR is a unique research tool as it provides nationwide detailed administrative and clinical data regarding in-hospital diagnosis and procedure codes based on the International Classification of Diseases 10th Revision (ICD-10) and the Nordic Classification of Surgical Procedures (NCSP), respectively.