Hybrid revascularization, comprising coronary artery bypass graft with exclusive arterial conduits followed by early drug-eluting stent implantation, in multivessel coronary artery disease

Archives of Cardiovascular Disease (2010) 103, 502—511

CLINICAL RESEARCH

Hybrid revascularization, comprising coronary artery bypass graft with exclusive arterial conduits followed by early drug-eluting stent implantation, in multivessel coronary artery disease Revascularisation coronaire hybride combinant pontage « exclusivement artériel » et implantation précoce de stent actif chez les patients multi-tronculaires Cédric Delhaye a,c, Arnaud Sudre a, Gilles Lemesle a,c, Laure Vanesson a,c, Mohamad Koussa b, Georges Fayad b, Christophe Bauters a,c, Jean-Marc Lablanche a,c, Thomas Modine b,∗ a

Cardiovascular Department, CHRU de Lille, 59037 Lille cedex, France Department of Cardiovascular Surgery, hôpital cardiologique, CHRU de Lille, boulevard Professeur-Leclercq, 59037 Lille cedex, France c Faculté de médecine, université de Lille II, 59000 Lille, France b

Received 29 May 2010; received in revised form 20 August 2010; accepted 17 September 2010 Available online 10 November 2010

KEYWORDS Hybrid revascularization; Coronary bypass; Drug-eluting stent

Summary Aim. — To assess the feasibility and safety of a hybrid myocardial revascularization strategy combining ‘‘exclusive arterial’’ conventional coronary artery bypass grafting (CABG) followed by early drug-eluting stent (DES) implantation in multivessel coronary artery disease (CAD). Methods. — Eighteen consecutive patients with multivessel CAD were enrolled prospectively. Within 48 hours of CABG using left internal mammary artery (IMA) to left anterior descending (LAD) coronary artery with or without right IMA to non-LAD vessel in an open chest approach, DESs were implanted systematically in an additional vessel after a clopidogrel 300-mg preloading

Abbreviations: CABG, coronary artery bypass graft; CAD, coronary artery disease; DES, drug-eluting stent; IMA, internal mammary artery; LAD, left anterior descending; MIDCAB, minimally invasive direct coronary artery bypass; PCI, percutaneous coronary intervention; RE-MIDCAB, robotically enhanced minimally invasive direct coronary artery bypass; VG, vein graft; RCA, right coronary artery; CPB, cardiopulmonary bypass; MACE, major adverse cardiac events; MI, myocardial infarction; TVR, target vessel revascularization; CK, creatinine kinase; ULN, upper limit of normal; TIMI, thrombolysis in myocardial infarction. ∗ Corresponding author. Fax: +33 32 04 6065. E-mail address: [email protected] (T. Modine). 1875-2136/$ — see front matter © 2010 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.acvd.2010.09.003

Exclusive arterial conduit CABG and early DES placement

503

dose. This group was compared with 18 matched patients who underwent standard CABG alone using left IMA to LAD and at least one additional graft. Results. — Baseline clinical characteristics were similar in both groups. There were 46 grafts in the CABG group and 28 in the hybrid group. In the hybrid group, 27.8% of patients were treated off-pump versus none in the CABG group; a median of 2 (interquartile range: 1—2) stents was implanted per patient. The hybrid procedure was associated with shorter durations of cardiopulmonary bypass (77 [67—100] min versus 97 [90—105] min, P = 0.049). Major bleeding rates were higher in the CABG group, but the difference was not statistically significant (44.4% versus 11.1%, P = 0.06). Re-intervention for bleeding was not needed in either group. One (5.6%) myocardial infarction occurred in hospital in each group following CABG. At 1 year, the cumulative rates of major adverse cardiac events (death, myocardial infarction, target vessel revascularization) were similar (11.2% in hybrid group versus 5.6% in CABG group, P = 0.99). One death occurred in the CABG group and one target vessel revascularization in the hybrid group. Conclusion. — A hybrid revascularization strategy, combining conventional CABG with exclusive arterial conduits followed by early DES implantation, is feasible. One-year event rates compare favourably to those with traditional CABG alone. © 2010 Elsevier Masson SAS. All rights reserved.

MOTS CLÉS Revascularization hybride ; Pontage coronaire ; Stent actif

Résumé Objectifs. — Évaluer la faisabilité et la sécurité d’une stratégie de revascularisation myocardique hybride combinant pontage coronaire (PC) « exclusivement artériel », suivi de l’implantation précoce d’un ou de plusieurs stents actifs (SA) chez des patients présentant une atteinte multitronculaire. Méthodes. — Dix-huit patients présentant une maladie coronaire multitronculaire ont été inclus de manière prospective. Dans les 48 heures suivant la réalisation d’un PC à thorax ouvert (artère mammaire interne (AMI) gauche greffée sur l’artère interventriculaire antérieure [IVA] ± AMI droite sur un autre vaisseau que l’IVA), au moins un SA était systématiquement implanté sur une des lésions non pontées après une dose de charge de 300 mg de clopidogrel. Ce groupe était comparé à 18 patients appariés ayant bénéficié uniquement d’un PC traditionnel associant AMI gauche greffée sur l’IVA et au moins une veine durant la même période. Résultats. — Les caractéristiques cliniques de base étaient similaires dans les deux groupes. Il y avait 46 greffons dans le groupe PC seul et 28 greffons dans le groupe hybride, avec une médiane de 2 [25—75e percentile : 1—2] stents implantés par patient. Dans le groupe hybride, 27,8 % des patients étaient traités à cœur battant, alors qu’aucun patient ne l’était dans le groupe PC seul. Ainsi pour les patients opérés sous circulation extracorporelle (CEC), la procédure hybride était associée à des durées plus courtes de CEC (77 [67—100] minutes versus 97 [90—105] minutes ; p = 0,049). Le taux de saignement majeur avait tendance à être plus élevé dans le groupe PC seul (44,4 % versus 11,1 % ; p = 0,06). Il n’y avait pas de réintervention pour cause de saignements dans les deux groupes. Un (5,6 %) infarctus du myocarde est survenu en milieu intrahospitalier dans le groupe PC seul. Aucune complication de l’angioplastie n’était constatée dans le groupe hybride. À un an, le taux cumulé d’évènement cardiaque indésirable défini comme l’association de décès, infarctus du myocarde et revascularisation du vaisseau cible était similaire dans les deux groupes (11,2 % dans le groupe hybride versus 5,6 % dans le groupe PC seul ; p = 0,99). Un décès était constaté dans le groupe PC seule et une revascularisation du vaisseau cible dans le groupe hybride. Conclusion. — Une stratégie de revascularisation hybride combinant PC exclusivement artériel suivi de l’implantation précoce de SA apparaît comme faisable et semble être, à un an, au moins aussi sûre et efficace qu’une revascularisation par PC seul. © 2010 Elsevier Masson SAS. Tous droits réservés.

Introduction Coronary artery bypass graft (CABG) surgery, involving grafting of the left internal mammary artery (IMA) to the left anterior descending (LAD) artery with additional vein graft (VG), remains the standard technique for treatment of multivessel coronary artery disease (CAD) [1—3]. The left IMA

grafted to the LAD provides the best long-term patency and survival benefit over percutaneous coronary intervention (PCI) for treating LAD stenosis [4,5]. As recent studies have reported a high rate of VG occlusion, which can reach >25% within 12—18 months [6,7], the long-term outcome of VGs has been questioned. The advent of PCI with drug-eluting stents (DES) [8] has resulted in a reduction in restenosis

504

C. Delhaye et al.

Table 1 Two-stage hybrid-procedurea studies, comprising coronary artery bypass graft followed by percutaneous coronary intervention. Lead author (year)

nb

Surgical procedure

Delay between CABG and PCI

Delay between CABG and PCI (range)

DES use

Lloyd et al. (1999) [32]

14

MIDCAB

NR

From 1—3 days

No

Wittwer et al. (2000) [33]

35

MIDCAB

7 days (median)

NR

No

Stahl et al. (2002) [8]

35

RE-MIDCAB

16 days (mean)

No

Riess et al. (2002) [34]

53

MIDCAB

5 days (median)

From 18 hours to 3 months From 2—7 days

No

Davidavicius et al. (2005) [35]

6

RE-MIDCAB

NR

In-hospital to 160 days

Yes, 1 patient only

Katz et al. (2006) [36]

12

RE-MIDCAB

16 days (mean)

From 2—60 days

Yes, 63% of patients

Holzhey et al. (2008) [37]

59

NR

From 2—45 days

Yes

Gao et al. (2009) [38]

10

RE-MIDCAB or MIDCAB RE-MIDCAB

NR

From 4—5 days

Yes, 20% of patients

CABG: coronary artery bypass graft; DES: drug-eluting stent; MIDCAB: minimally invasive direct coronary artery bypass; NR: not reported; PCI: percutaneous coronary intervention; RE-MIDCAB: robotically enhanced minimally invasive direct coronary artery bypass. a In separate rooms. b Number of patients who underwent the two-stage hybrid procedure.

rates and the need for repeat revascularization versus PCI with bare-metal stents, with a 12-month restenosis rate making this revascularization technique an attractive option compared with VGs [9—12]. Both CABG and PCI have their limitations and advantages, but rather than viewing them as mutually exclusive, there may be a role for their combined use in specific patient populations. Recent studies have reported the feasibility and safety of a simultaneous hybrid coronary revascularization technique combining CABG with left IMA to LAD and DES implantation for treating multivessel CAD [13—17], but owing to logistical and practical concerns, few teams have been able to provide it. Given these considerations, a two-stage revascularization process combining CABG and DES implantation could offer a more realistic alternative. Several teams have reported the feasibility of performing CABG followed by PCI (Table 1). However, these studies used either a minimally invasive direct coronary artery bypass (MIDCAB) or robotically enhanced-MIDCAB (RE-MIDCAB). Besides sizeable logistical issues making these techniques available for only a restricted number of teams, this minimally invasive surgery is limited mostly to revascularization of the LAD territory, as the circumflex and right coronary arteries (RCAs) are less accessible. Using a hybrid approach involves revascularization of all of the other vessels by PCI, but even in the ‘‘DES era’’, PCI remains limited to suitable anatomical lesions. The use of the right IMA in addition to left IMA grafting with a conventional open chest approach has been shown to provide long-term benefits when compared with revascularization using a single left IMA and VG [18—20]. Thus a hybrid revascularization combining ‘‘exclusive arterial’’ CABG with DES implantation — the most successful applications of surgical and percutaneous techniques in patients with multivessel CAD — appears very attractive. Besides

avoiding non-arterial grafts, this hybrid approach could be helpful in cases of poor or non-harvestable grafts as well as for reducing the duration of surgery. Here, we report the feasibility, safety and outcomes of a hybrid revascularization strategy combining conventional CABG with exclusive arterial conduits (left IMA to LAD with or without right IMA to non-LAD vessel) with a conventional open chest approach, followed by early DES implantation, in patients with multivessel CAD. This revascularization strategy was compared with a conventional approach using CAGB alone.

Methods Study population Between October 2006 and January 2008, 18 patients with multivessel CAD were enrolled prospectively to undergo myocardial revascularization. The hybrid strategy associated CABG with exclusive arterial conduits (left IMA to LAD with or without right IMA to non-LAD vessel) followed, within 48 hours, by DES implantation in an additional vessel. Inclusion criteria for hybrid revascularization were the presence of multivessel CAD, a >70% LAD obstruction judged suitable for surgery, and the presence of a non-LAD lesion(s) suitable for either right IMA graft and PCI, or PCI only. Patients not suitable for treatment with dual antiplatelet therapy (aspirin plus clopidogrel) for at least 1 year, those taking an oral anticoagulant, and patients scheduled for surgery within 1 year after PCI were excluded. All cases were validated by both the surgeon and the interventional cardiologist.

Exclusive arterial conduit CABG and early DES placement Using a prospective case-controlled study design, a parallel control group of 18 patients who underwent conventional CABG alone (left IMA to LAD and additional grafts for nonLAD vessels: VG for double bypass and VG plus right IMA for triple bypass) during the same period of time was matched, according to sex, age, diabetes, clinical presentation and number of treated vessels. All patients provided informed consent to be enrolled in the study and to anonymous data analysis. The study was approved by and registered with the local ethics committee.

Surgical procedure Pharmacological management All patients were given oral antiplatelet therapy with aspirin 160 mg/day before and after CABG. Patients taking clopidogrel stopped this treatment 5 days before the CABG procedure. Preoperative statin therapy was given systematically. Systemic treatment with unfractionated heparin was given after internal mammary harvesting: 300 U/kg for on-pump CABG surgery and 100 U/kg for off-pump CABG. Heparin was antagonized with protamine sulphate at a ratio of 1:1 upon completion of distal and proximal coronary anastomosis or weaning of the cardiopulmonary bypass (CPB) in both groups.

Surgery Median sternotomy was performed in all patients. The left IMA was harvested, together with additional graft material (right IMA and/or VG). The decision to use either on-pump or off-pump CABG was left to the discretion of the surgeon.

On-pump coronary artery bypass graft surgery Intermittent cold blood hyperkaliemic cardioplegia and moderate hypothermia (33 ◦ C) were used in all CABG patients. During CPB, the mean arterial pressure was allowed to vary between 60 and 90 mmHg. Tight glycaemic control (<1.5 g) was observed until discharge.

Off-pump coronary artery bypass graft surgery Stabilization of the beating heart was established with the Octopus III® (Medtronic Inc., Minneapolis, MN). Heart displacement into varied grafting positions was aided by the use of deep pericardial retraction sutures facilitating exposure of lateral and posterior walls. The Trendelenburg’s position was used and the table tilted when necessary. No apical suction devices were used to assist immobilization. Intracoronary shunts were not used in this study.

Percutaneous coronary intervention procedure for hybrid revascularization Coronary stenting was performed using conventional techniques, within 48 hours of CABG. The interventional strategy was left to the discretion of the operator. In all cases, a femoral approach was employed. All patients underwent postoperative angiography to demonstrate patency of the grafts at the time of the PCI. Intraprocedural anticoagulation was ensured using unfractionated heparin with a bolus of 40—50 U/kg. Glycoprotein IIb/IIIa inhibitors were not used. All patients received aspirin 160 mg/day before the procedure and continued this regimen indefinitely. All

505 patients received a clopidogrel loading dose of 300 mg, 6 hours before PCI, followed by a maintenance dose of 75 mg/day after PCI for at least 1 year. The sheath was removed at the end of the procedure using manual compression or an arterial closure device.

Follow-up and definition endpoints All patients attended routine clinical follow-up and were contacted by a nurse to assess long-term clinical outcome. The primary endpoint was the 1-year rate of major adverse cardiac events (MACE) defined as the composite of death, myocardial infarction (MI) and target vessel revascularization (TVR). Death was defined as all-cause mortality. MI was defined as creatinine kinase (CK) ≥5 times the upper limit of normal (ULN) within 24 hours after CABG, CK ≥3 times the ULN within 24 hours after PCI, and thereafter as CK ≥2 times the ULN and/or ischaemic electrocardiographic changes including ST elevation ≥1 mm or new Q-waves. TVR was characterized by ischaemia-driven percutaneous or surgical revascularization of the treated vessel. Definite stent thrombosis was considered as defined by the Academic Research Consortium [21]. Procedural success was defined as attainment of both thrombolysis in myocardial infarction (TIMI) flow grade 3 and a residual stenosis <30%. Major bleeding was defined as the TIMI study group definition, i.e. a decrease in haematocrit of ≥15% and/or the occurrence of intracranial bleeding [22]. CABG-related bleeding was included in the definition.

SYNTAX score calculation The SYNTAX score is an angiographic tool that allows clinicians to grade the complexity of CAD: the higher the score, the more complex the disease. The SYNTAX score for each patient was calculated retrospectively by two interventional cardiologists blinded to the group assignment. All coronary lesions with a diameter stenosis of ≥50% in vessels of ≥1.5 mm were scored according to the SYNTAX score algorithm, which has been described elsewhere [23] and is available on the SYNTAX score website (www.syntaxscore.com) [24].

Statistical analysis Continuous variables are shown as medians (25—75th percentiles). Categorical variables are expressed as percentages. The Mann-Whitney test was used to compare continuous variables and the Chi2 test or Fisher’s exact test to compare categorical variables. Statistical significance was assumed at P < 0.05. All analyses were conducted using SPSS 11.0 software (SPSS Inc., Chicago, IL, USA).

Results Patients’ characteristics Patients’ baseline characteristics are shown in Table 2. There were no differences in the baseline characteristics of patients in the CABG group and those in the hybrid group. Sixteen (88.9%) patients in both groups had three-vessel CAD.

506 Table 2

C. Delhaye et al. Patients’ baseline characteristics.

Variable

CABG group(n = 18)

Hybrid group(n = 18)

P

Demographic Age (years) Female sex

60 (53—68) 4 (22.2)

62 (55—70) 4 (22.2)

0.36 1.00

Cardiovascular risk factor Diabetes mellitusa Hypertensionb History of smoking Body mass index (kg/m2 ) Hypercholesterolaemiac Chronic renal failured

7 14 7 27 12 1

8 12 8 28 15 0

(44.5) (66.7) (44.4) (23—31) (83.3) (0%)

0.74 0.71 0.36 0.91 0.44 1.00

(11.1) (27.8) (0.0) (27.8)

0.49 0.69 — 0.69

Cardiovascular history Stroke Myocardial infarction CABG Peripheral vascular diseasee

0 3 0 3

(38.9) (77.8) (38.9) (24—31) (66.7) (5.6) (0) (16.7) (0.0) (16.7)

2 5 0 5

Indication for PCI Stable angina Acute coronary syndrome

5 (27.8) 13 (72.2)

8 (44.4) 10 (55.6)

0.30 0.30

Left ventricular ejection fraction (%)

60 (55—65)

60 (54—65)

0.84

Three-vessel disease

16 (88.9)

16 (88.9)

1.00

Baseline haemoglobin

13.6 (12.0—15.0)

12.7 (11.8—13.9)

0.17

MI: myocardial infarction; CABG: coronary artery bypass graft; LVEF: left ventricular ejection fraction; PCI: percutaneous coronary intervention. Data expressed as median (25—75th percentile) or number (%). a Any history of diabetes mellitus and/or use of hypoglycaemic drugs, and including a new diagnosis made during the index hospitalization with a fasting glucose level of ≥1.26 g/l on ≥2 separate occasions. b History of hypertension diagnosed and/or treated with medication or currently being treated with diet and/or medication by a physician. c Includes patients with a previously documented diagnosis of hypercholesterolaemia. The patient may be treated with diet or medication. A new diagnosis can be made during this hospitalization with an elevated total cholesterol >160 mg/dl; does not include elevated triglycerides. d Defined as clearance creatinine ≤60 ml/min calculated using the Cockroft-Gault equation. e Defined as presence of classic claudication, history of peripheral vascular surgery or non-traumatic amputations.

Operative and percutaneous coronary intervention characteristics Operative and PCI characteristics are given in Table 3 and a summary of the grafts in Table 4. Forty-six grafts were done in the CABG group and 28 in the hybrid group (Table 4). The SYNTAX score was similar in both groups (P = 0.23). All 18 patients in the CABG group and 13 in the hybrid group underwent on-pump CABG. In the five patients treated with off-pump CABG, four underwent left IMA to LAD bypass only and the fifth had left IMA to LAD and right IMA to diagonal branch. In patients with on-pump CABG, the hybrid procedure was associated with shorter CBP time (P = 0.04). In the hybrid group, angiographic success was achieved in 96.6% of patients; there was one PCI failure because of the inability to cross the lesion (distal RCA) with a wire. There were no PCI complications. Twenty-six of the 29 lesions were ‘‘on label’’ according to the French guidelines for DES indication [25]. On checking the CABG, one anastomotic defect was found on a right IMA graft to obtuse marginal and one proximal occlusion of a right IMA graft to obtuse

marginal; both patients were treated medically because they are unsuitable for PCI. No defects were found in the left IMA graft.

Clinical outcomes In-hospital bleeding and vascular complications are reported in Table 5. All patients in the hybrid group who received a loading dose of clopidogrel after CABG underwent PCI. Although not statistically significant, the rates of major bleeding and need for transfusion were higher in the CABG group than in the hybrid group (respectively, 44.4% versus 11.1%, P = 0.06; 39.3% versus 11.1%, P = 0.23). No patients required re-intervention for bleeding or tamponade. The median length of hospitalization was similar in the two groups. Three patients in the CABG group and none in the hybrid group (P = 0.23) reported a 25% worsening in baseline serum creatinine at 5 days after discharge from the CABG operative room. In-hospital and 1-year outcomes are reported Table 6. One in-hospital MI occurred in each group. In the hybrid

Exclusive arterial conduit CABG and early DES placement Table 3

507

Operative and percutaneous coronary intervention characteristics.

Variable (patient-based)

CABG group(n = 18)

Hybrid group(n = 18)

P

SYNTAX score

24.0 (17.7—30.0)

25.2 (22.2—37.9)

0.23

CABG characteristic Number of arterial grafts per patient Number of VGs per patient Off-pump CABG CBP time, if applicable, (min)

2 (1—2) 1 (1—1) 0 (0.0) 97 (90—105)

2 (1—2) 0 5 (27.8) 77 (61—100)

1.00 — 0.04 0.04

PCI (within 48 hours of CABG) Dose of unfractionated heparin (U) Number of dilated lesions Number of DES implanted per patient Closure device Contrast amount (ml) Fluoroscopy time (min) Dose area product (Gray/cm2 ) Time between discharge from CABG operative room and PCI (hours)

— — — — — — — —

Variable (lesion-based) Target coronary vessel Left main LADa OM RCA VG Left IMA/right IMA Type B2/C lesion (ACC/AHA class)

2650 2 2 5 175 10 72 41

(2400—3000) (1—2) (1—2) (27.8) (145—245) (7—17) (41—111) (37—44)

Hybrid group (n = 29) (6.9) (3.5) (31.0) (58.6) (0.0) (0.0) (68.9)

— — — — — —

P

— — — — — —

2 1 9 17 0 0 20

— — — — — —

Calcificationb None Moderate Severe

— — —

12 (14.5) 11 (13.5) 6 (7.2)

Angiographic success

—

28 (96.6)

—

PCI complication No reflowing Abrupt closure Dissection

— — —

0 (0.0) 0 (0.0) 0 (0.0)

—

Restenosis lesion

—

1 (3.4)

—

Lesion length (mm)

—

10 (14—19)

Reference vessel diameter (mm)

—

2.7 (2.5—3.3)

Stent length (mm)

—

12 (12—17)

—

Stent diameter (mm)

—

2.5 (2.5—3.0)

—

Minimal lumen diameter before procedure (mm)

—

0.64 (0.43—0.94)

—

Minimal lumen diameter after procedure (mm)

—

2.90 (2.48—3.06)

—

Preprocedural % diameter stenosis

—

77 (65—84)

—

Post-procedural % diameter stenosis

—

1 (0—5)

—

ACC/AHA: American College of Cardiology/American Heart Association; CBP: cardiopulmonary bypass; DES: drug-eluting stent; IMA: internal mammary artery; LAD: left anterior descending; OM: obtuse marginal; RCA: right coronary artery; UFH: unfractionated heparin; VG: vein graft. Data expressed as median (25—75th percentile) or as number (%). a One patient had both grafting of the distal LAD and stenting for a proximal lesion. b Calcification was identified as readily apparent radio-opacities within the vascular wall at the site of the lesion and was classified as none, moderate (radio-opacities noted only during the cardiac cycle before contrast injection) and severe (radio-opacities noted without cardiac motion before contrast injection generally compromising the two sides of the arterial lumen).

508 Table 4

C. Delhaye et al. Summary of grafts.

Variable

CABG group

Hybrid group

Grafts

46

28

Patients with double bypass Left IMA to LAD VG to OM or RCA

8 8 5 OM, 3 RCA

8 8 DES

Patients with triple bypass Left IMA to LAD Right IMA to OM, DB or RCA VG to RCA

10 10 9 OM, 1 DB 10

10 10 7 OM, 2 DB, 1 RCA DES

DB: diagonal branch; DES: drug-eluting stent; LAD: left anterior descending artery; IMA: internal mammary artery; OM: obtuse marginal; RCA: right coronary artery; VG: vein graft. Data expressed as number.

Table 5

In-hospital bleeding and vascular complications.

Variable

CABG group(n = 18)

Hybrid group(n = 18)

P

Bleeding complication Total postoperative drain output (ml) Post-clopidogrel LD drain output (ml) Re-intervention for bleeding or tamponade Need of transfusion Intracerebral bleeding Haemoglobin drop (g/dl) Haemoglobin drop ≥5 g/dl Major bleeding

1010 (685—1250) — 0 (0.0) 6 (39.3) 0 (0.0) 4.2 (2.7—5.9) 8 (44.4) 8 (44.4)

950 (732—154) 185 (60—312) 0 (0.0) 2 (11.1) 0 (0.0) 2.4 (1.5—4.2) 2 (11.1) 2 (11.1)

0.88 — — 0.23 — 0.008 0.06 0.06

0 (0) 10.5 (10.0—12.5) 3 (17)

0 (0) 10.0 (10.0—11.2) 0 (0)

— 0.33 0.23

Vascular complication Median length of hospital stay from CABG (days) 25% worsening of baseline serum creatinine 5 days after surgery

CABG: coronary artery bypass graft; LD: loading dose. Data expressed as median (25—75th percentile) or as number (%).

Table 6

In-hospital and 1-year ischaemic outcomes.

Variable

CABG group(n = 18)

Hybrid group(n = 18)

P

In-hospital event Death MI TVR MACE (death/MI/TVR)

0 1 0 1

(0.0) (5.6) (0.0) (5.6)

0 1 0 1

(0.0) (5.6) (0.0) (5.6)

— 1.00 — 1.00

Cumulative 1-year events Death MI Death/MI TVR MACE (death/MI/TVR) Stent thrombosis Stroke

1 (5.6) 1 (5.6) 1 (5.6) 0 (0.0) 1 (5.6) — 0 (0.0)

0 1 1 1 2 0 0

(0) (5.6) (5.6) (5.6) (11.2) (0.0) (0.0)

1.00 1.00 1.00 1.00 0.99 — —

MACE: major adverse cardiac event; MI: myocardial infarction; TVR: target vessel revascularization. Data expressed as n (%).

Exclusive arterial conduit CABG and early DES placement group, in-hospital MI was diagnosed with a rise in CK within 24 hours after CABG and was related to a middle RCA subocclusion, which underwent PCI the following day. In-hospital rates of MACE were the same, and were due to the inhospital MIs. At 1 year, there was one (5.6%) death in the CABG group and one TVR (5.6%) in the hybrid group; the cumulative rates of MACE were similar (P = 0.99).

Discussion The main finding of this study is that hybrid revascularization, combining conventional CABG with exclusive arterial conduits and a conventional open chest approach followed by early DES implantation, is feasible in patients with multivessel CAD. Moreover, this approach appears as safe and as effective as that of standard management by CABG alone, with identical 1-year outcomes. Starting with CABG and following with PCI offers several advantages over the reverse strategy. First, it avoids bleeding complications, as treatment with clopidogrel plus aspirin before CABG is associated with higher rates of postoperative bleeding and morbidity [26—29]. In spite of a clopidogrel loading dose given within 48 hours of CABG in all patients in the hybrid group, the rate of bleeding was not higher than that in the conventional CABG group, and even tended to be lower. Indeed, although not statistically significant, there was a greater than three fold decrease in the need for transfusion, and the rate of major bleeding was higher in the CABG group, as reflected by the greater drop in haemoglobin. This difference may be explained by the more frequent use of off-pump CABG and the 20% decrease in the CBP time in the hybrid group, which was probably related to the reduced number of grafts. However, these results should be interpreted with caution given the small sample size of the study. As shown in Table 1, most studies using less invasive CABG techniques performed the PCI some time after the surgery (>48 hours). In the present study, we show that PCI with a clopidogrel preloading dose can be performed within 48 hours of conventional open chest CABG surgery without increasing the bleeding risk compared with a more traditional approach. This revascularization sequence did not affect the length of hospital stay, which appeared similar between the hybrid group and the CABG group. Secondly, by starting the hybrid procedure with CABG allowed the PCI to be performed in a ‘protected’ environment, especially with regards to the anterior myocardial wall. This protection makes PCI suitable even for the left main, which was done in one patient. Finally, this revascularization strategy allowed clinicians to check the patency of the graft at the time of PCI, although the defects identified at this time could not be always resolved with PCI. In our cohort, two patients had defects (one anastomotic defect and one occlusion) on the right IMA to obtuse marginal, which were treated medically. Concerns exist regarding the performance of PCI within 48 hours of CABG. The first is the risk of coronary ischaemic events occurring in the inflammatory postoperative period. No cases of stent thrombosis occurred in our small cohort, in which every patient received a clopidogrel loading dose before PCI. However, one patient experienced MI after the CABG, related to a subocclusion of the vessel planned for

509 treatment by PCI on the following day. In addition, the rate of in-hospital MI was similar between the hybrid approach and the standard CABG approach. The second concern is the possibility of a PCI complication or failure resulting in the need for a second and much higher risk surgical procedure. Nevertheless with improvements in the technique, the risks of complications relating to PCI and stent failure with the need for emergency bypass surgery have become very rare [30]; we observed a high angiographic success rate, around 97%, in our cohort and encountered no PCI complications. Several research teams have reported their experience of the hybrid approach with DES, using either a simultaneous sequence [13—17] or combining two-stage CABG followed by PCI using MIDCAB or RE-MIDCAB (Table 1). In the present study, we show that it is safe to perform DES implantation just after conventional open chest CABG with a clopidogrel preloading dose. No difference between the hybrid group and the standard CABG group (using VG) was found in terms of 1-year MACE, and we confirm the good clinical outcome of DES [9—12], with no cases of clinical restenosis at 1 year. The TVR at 1 year was due to an atherosclerotic plaque rupture located far away from the stent. Finally, the complexity of the CAD was similar between the hybrid group and the CABG group, as shown by the SYNTAX scores (25.2 and 24.0, respectively, P = 0.23). In the SYNTAX study, patients with multivessel CAD and a SYNTAX score ≥23 had a higher rate of major adverse cardiovascular and cerebrovascular events after PCI than after CABG [23]. In the randomized SYNTAX study, >80% of the patients in the CABG group underwent at least one VG [31]. Owing to concerns about VG outcome [6,7], it is plausible that combining the best of modern revascularization techniques such as exclusive mammary arterial conduit CABG and DES implantation could improve clinical outcome, especially in multivessel CAD patients in whom the SYNTAX score is >23.

Limitations The main limitation of our study is the small size of the cohort, which may have resulted in a failure to recognize minor differences between the hybrid group and the standard CABG group. Indeed, the hybrid approach has not yet been widely validated, and thus was difficult to justify for patients and colleagues. Moreover, PCI was supposed to be performed within 48 hours after CABG, leading to problems with the inclusion of patients towards the end of the working week. Another limitation is the lack of systematic angiographic control of graft and stent patency at 1-year follow-up, which may also have been too short to identify a difference in outcomes. A definitive comparison would, however, require a large, prospective, randomized trial with long-term follow-up, which is itself a compelling challenge. Finally, all patients in the CABG group underwent on-pump CABG, which may have been responsible for the higher morbidity, such as bleeding. However, patients in this control group represent the usual surgical practice in our centre, in which >500 CABG procedures are performed annually.

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Conclusions The hybrid procedure, combining open chest CABG with ‘‘exclusive arterial conduit(s)’’ followed by early DES implantation, is feasible, and appears safe and effective in selected patients with multivessel CAD, with a satisfactory 1-year performance compared with conventional CABG alone.

[14]

[15]

[16]

Conflict of interest statement None. Funding: INTERREG III, FEDER project EEC.

[17]

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