Side branch occlusion after coronary stent implantation in patients presenting with ST-elevation myocardial infarction

Side branch occlusion after coronary stent implantation in patients presenting with ST-elevation myocardial infarction: Clinical impact and angiographic predictors Stefan Kralev, MD, Tudor C. Poerner, MD, Daniel Basorth, MD, Siegfried Lang, PhD, Christian Wolpert, MD, Dariusch Haghi, MD, Martin Borggrefe, MD, Karl K. Haase, MD, FACC, and Tim Su ¨ selbeck, MD Mannheim, Germany

Background The aim of this study was to assess the incidence and clinical outcome of the occlusion of major (N1 mm) side branches following coronary stenting in patients undergoing percutaneous coronary intervention for acute ST-elevation myocardial infarction (STEMI). Methods

Among 276 consecutive patients presenting with STEMI, we found 80 patients (29%) with 101 stent-covered side branches. Clinical data and quantitative angiographic analysis were evaluated. Angiographic follow-up was available in 56 (70%) patients, and clinical follow-up could be completed in all patients.

Results

Acute side branch occlusion after stent implantation (SBO) was observed in 10 (12.5%) patients involving 11 (10.9%) side branches. Predictors for SBO were: (1) reference side branch diameter at baseline V1.4 mm; (2) ostial side branch stenosis N50%; and (3) minimal side branch diameter at baseline V 0.6 mm. During hospitalization, in the SBO group, 2 patients died in cardiogenic shock and 1 underwent bypass surgery; no events were causally related to SBO. During long-term follow-up, 1 patient with SBO developed repeat MI as opposed to 7 patients in the non-SBO group who developed major adverse cardiac events (1 death, 6 repeat revascularizations).

Conclusions The presence of a side branch originating from the target lesion in patients undergoing coronary stenting for acute STEMI is a frequent observation (29%) and is associated with a low incidence of side branch occlusion. Major predictors for SBO are the side branch size and the presence of an ostial side branch stenosis. (Am Heart J 2006;151:153 - 7.) A current problem of stent implantation in patients presenting with ST-elevation myocardial infarction (STEMI) constitutes the involvement of a side branch that originates within the target lesion. Several studies have identified side branch occlusion (SBO) after stent implantation as a cause of postinterventional creatine kinase (CK) or troponin increase1-4; even minimal CK or troponin increase is associated with an increased incidence of cardiac events in the first year. Previous

From the First Department of Medicine, University Hospital of Mannheim, Mannheim, Germany. Drs Kralev and Poerner contributed equally to the work. There is no conflict of interest or financial statement that should be disclosed. Submitted August 28, 2004; accepted January 19, 2005. Reprint requests: Stefan Kralev, MD, 1. Medizinische Universita ¨ tsklinik, Klinikum Mannheim gGmbH, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. E-mail: [email protected] 0002-8703/$ - see front matter n 2005, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2005.01.034

studies investigated patients undergoing elective stent implantation and showed an incidence of about 20% for SBO.5-11 In these studies, predictors for SBO were (1) the reference diameter of the side branch, (2) the prevalence of a stenosis at the origin of the side branch, (3) TIMI flow grade b3, (4) lesion length, (5) diabetes, and (6) stent dilation using high-pressure inflations. At present, however, there are no studies that focus on the patency of side branches in patients presenting with STEMI. Thus, it was the aim of this study to define predictors for SBO after target lesion stent implantation in patients presenting with STEMI.

Methods Study design The study was prospectively conducted. Eligible were all patients suitable for primary or rescue percutaneous coronary intervention (PCI) for STEMI and who have side branches with takeoff within the target lesion. Stent implantation and use of glycoprotein IIb/IIIa antagonists were attempted in all patients.

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Table I. Baseline clinical data

Age Male sex Hypertension Family history Diabetes mellitus Cigarette smokingT Hypercholesterolemia Obesity Prior myocardial infarction Prior bypass surgery Prior PCI 1-Vessel disease 2-Vessel disease 3-Vessel disease

Table II. Procedural data

Patients with SBO (n = 10)

Patients without SBO (n = 70)

58.5 F 10.2 6 (70%) 5 (50%) 2 (20%) 1 (10%) 5 (50%) 5 (50%) 1 (10%) 1 (10%) 0 (0%) 1 (10%) 3 (30%) 3 (30%) 4 (40%)

60.6 F 10.8 53 (76%) 36 (51%) 12 (17%) 10 (14%) 31 (44%) 45 (64%) 16 (23%) 8 (11%) 3 (4%) 4 (6%) 37 (53%) 25 (36%) 8 (11%)

All P values N.10. THistory of cigarette smoking during last 3 months.

Cardiogenic shock at first presentation and side branch protection by guide wires or subsequent side branch dilation during the angioplasty procedure were exclusion criteria. Percutaneous coronary intervention goals were (1) reperfusion with TIMI III flow of the infarct-related artery and (2) an optimal angiographic stent result of the target lesion, irrespective of the perfusion status of lesion-related side branches. ST-elevation myocardial infarction management was carried out according to American College of Cardiology/American Heart Association guidelines.12

Patients From January 2002 to December 2003, we evaluated 276 patients presenting with STEMI. Among them we found 80 patients with a side branch originating from the target lesion. Before the intervention, all patients were given aspirin, either as long-term therapy (100 mg/d) or at an initial intravenous dose of 500 mg. A glycoprotein IIb/IIIa antagonist could be administered to 73 (91%) of the patients. During intervention, heparin was given to maintain an activated clotting time in a range between 200 and 300 seconds. The choice of the stent device was made at the examiner’s discretion and stents were implanted using pressures N12 atm. All stented patients were given 300 mg of clopidogrel immediately after the intervention and remained on clopidogrel at a dose of 75 mg for 28 days. Inhospital serial electrocardiograms and peak and postinterventional CK and troponin I levels were recorded. Longterm clinical and angiographic follow-up was attempted in all patients. Major adverse cardiac events (MACEs) were defined as death, myocardial infarction, and repeat revascularization (coronary bypass surgery, inhospital stent thrombosis and target lesion revascularization at long-term follow-up).

Angiographic analysis Angiograms were reviewed by 2 independent observers to identify target vessels with major side branches (N1 mm in diameter) that were covered by stents. The angiographic results were evaluated by quantitative coronary angiographic

Time to reperfusion (h)T Door-to-balloon time (min) Thrombolysis (rescue PCI) Use of glycoprotein IIb/IIIa inhibitors Activated clotting time (s) No. of stents per lesion DS CS Stent types (% of total stent number) JO stenty AVE stentz Multilink stent§ Length of the stent (mm) Maximal inflation pressure (atm) Balloon-to-artery ratio

Patients with SBO (n = 10)

Patients without SBO (n = 70)

4F2 48 F 20 1 (10%) 8 (80%)

3.5 F 2.5 44 F 31 7 (10%) 65 (93%)

293 F 49 1.0 3 (30%) 7 (70%)

287 F 51 1.1 33 (47%) 47 (67%)

5 (50%) 0 (0%) 5 (50%) 18.4 F 5.1 15.3 F 1.8

56 (70%) 6 (7%) 18 (23%) 16.7 F 3.6 15.2 F 2.1

1.21 F 0.18

1.24 F 0.20

All P values N .10. TTime interval from beginning of acute symptoms to successful reperfusion of the infarct-related artery. yJomed. zMedtronic. §Guidant Corporation.

analysis using the software Quantcor QCA (Siemens AG, Munich, Germany). All frames were calibrated with the tip of the guiding catheter—before injection of contrast medium—as a reference. Two orthogonal projections were used after wire passage and after stent implantation at the end of the interventional procedure. For every evaluated vascular area, standard morphologic criteria13 such as proximal and distal reference lumen diameter (RLD), minimal lumen diameter (MLD), percentage of stenosis, TIMI flow, lesion length, qualitative degree of vessel curvature, presence of thrombus, and number of side branches were used. In the presence of a complete occlusion of the main vessel, the morphology of the side branch and the main vessel was evaluated initially after wire passage and subsequently after stent implantation. Side branches were also characterized on each frame by ostial and reference diameter, percentage of ostial stenosis, TIMI flow, and angulation related to the main vessel. Procedural data (balloon and stent types, inflation pressure, number of inflations) were recorded, and the balloon-to-artery ratio was calculated as the balloon diameter at maximal expansion/ reference diameter of the target vessel at baseline. Coronary perfusion was graded according to the classification system of the TIMI trial.14 Side branch occlusion was defined as a persistent TIMI flow V1.

Statistical analysis All continuous variables are presented as mean value F1 SD and analyzed using the Student t test in case of a normal distribution. The Mann-Whitney test was used for variables without normal distribution. Deviations from a Gaussian distribution were tested by using the Kolmogorov-Smirnov test. Categorical variables are expressed in percent and analyzed

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Table III. Location and fate of side branches Location Right ventricular Septal Diagonal Marginal Left posterior lateral Total

Side branches without occlusion 31 25 16 15 3

(34%) (28%) (18%) (17%) (3%) 90

Table V. Predictors for acute SBO Side branches with occlusionT 2 2 4 3

(18%) (18%) (36%) (28%) 0 11

TAll P values N.05.

Predictors for SBO Ostial side branch diameter stenosis N50% before stent implantation Reference side branch diameter at baseline V1.4 mm Minimal side branch diameter at baseline V0.6 mm

Relative risk

95% CIT

P

39.8

5.4-291

b.0001

7.14

0.95-53.6

48.3

6.6-350

b.05

b.0001

T95% CI of relative risk.

Table IV. Angiographic characteristics Acute SBO Present: 11 Absent: 80 side side branches branches in in 10 patients 70 patients Side branch Baseline (after wire passage) Reference diameter (mm)T Minimal luminal diameter (mm)y Ostial stenosis N50%z Final (after stenting) Reference diameter (mm) Follow-up§ Reference diameter (mm) Minimal luminal diameter (mm) Ostial stenosis N50% Target lesion Baseline (after wire passage) Reference diameter (mm) Minimal luminal diameter (mm) Diameter stenosis (%) Length of stenosis (mm) Final (after stenting) Reference diameter (mm) Minimal luminal diameter (mm) Diameter stenosis (%) Final TIMI 3 (no. of patients) Follow-upO Reference diameter (mm) Minimal luminal diameter (mm) Diameter stenosis (%) Final TIMI 3 (no. of patients)

1.18 F 0.14 0.50 F 0.35

1.37 F 0.40 1.14 F 0.48

10 (91%)

8 (10%)

Occluded

1.39 F 0.30

1.24 F 0.11 1.08 F 0.45

1.37 F 0.37 1.25 F 0.50

0

2 (3%)

2.97 F 0.49 0.27 F 0.25

3.09 F 0.43 0.33 F 0.36

89 F 10 9.57 F 3.7

88 F 13 10.4 F 4.4

3.11 F 0.36 2.85 F 0.39

3.19 F 0.38 2.84 F 0.56

6.13 F 6.18 9 (90%)

9.3 F 12.8 66 (94%)

3.12 F 0.49 2.74 F 1.32

3.24 F 0.41 2.72 F 1.06

14.6 F 39.3 6 (60%)

14.5 F 31.8 40 (57%)

TP b .05. yP b .001. zP b .0001. §Six side branches with late reperfusion. OFollow-up available in 10 patients with side branch occlusion and in 46 patients without side branch occlusion.

with a 2  2 table and Fisher’s exact test. Tables with categorical variables and more than 2 rows and 2 columns were analyzed by the m2 test. For all calculations, the statistical software SPSS for Windows (version 10.0.5, SPSS, Inc,

Chicago, IL) and InStat (GraphPad InStat version 3.00 for Windows 95, GraphPad Software, San Diego, CA) were used. Factors showing a P value b.15 on univariate regression were entered into a multivariable stepwise logistic regression model. Common odds ratio (OR) and the related 95% CIs were calculated and P values b.05 were accepted as statistically significant.

Results Study population This study reports a single-center experience investigating 276 unselected patients presenting with an acute STEMI. A total of 101 stent-covered side branches was found in 80 patients (29%). All side branches had a diameter N1 mm and were spanned by intracoronary stents. The clinical and demographic data of the patient population are listed in Table I. Side branch perfusion Altogether, 101 side branches emerging from 80 lesions with an RLD of 1.34 F 0.41 mm and an MLD of 1.03 F 0.50 mm were covered by 90 stents: 61 Jo stents (Jomed, Rangendingen, Germany), 6 AVE stents (Medtronic, Minneapolis, MN), and 23 Multilink stents (Guidant Corporation, Indianapolis, Ind). Procedural data are presented in Table II; anatomical localization is depicted in Table III. All side branches arose from the stenotic lesion. An ostium stenosis N50% was detected in 90% of the patients with SBO. After the intervention was completed, 11 functionally occluded side branches were detected in a total of 10 lesions. Ninety-seven percent of the side branches with an RLD N1.4 mm showed a normal antegrade perfusion after the intervention. On the other hand, only 81% of the side branches with an RLD b1.4 mm showed a complete perfusion ( P b .05). Table IV shows the short- and long-term angiographic features of the side branch and the target vessel. Three predictors for acute SBO after stent implantation could be identified: (1) reference side branch diameter at baseline, (2) ostial side branch stenosis before stenting,

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Table VI. Clinical outcome All patients with side branches (N = 80) Patients Patients with without SBO SBO (n = 10) (n = 70) Inhospital follow-up Death Repeat myocardial infarctionz Repeat revascularization (coronary artery bypass surgery, stent thrombosis) Long-term follow-up Death Repeat myocardial infarctionz Repeat revascularization (coronary artery bypass surgery, target lesion revascularization)

P

2 (20%)T 0

5 (7%)y 2 (3%)

.210 1.000

1 (10%)

3 (4%)

.420

0 0

1 (1%) 0

.261 1.000

1 (10%)

6 (9%)

.621

TBoth developing cardiogenic shock. yThree of them developing cardiogenic shock. zNot caused by infarct-related artery.

and (3) MLD at baseline (Table V). No significant correlation for SBO was found for thrombus, angulation of the main vessel, TIMI flow, prior use of thrombolytic agents, activated clotting time, stenting procedure (direct vs conventional), and angiographic evidence of dissection. Other interventional data such as the number and type of stents, maximal balloon pressure, number of inflations, balloon-to-artery ratio, and high-pressure dilation poststenting also had no influence on SBO Likewise, the anatomical localization of the side branches (Table III) as well as the existence of several side branches per lesion did not show a correlation with acute SBO. Furthermore, clinical variables such as coronary risk factors or extent of coronary artery disease did not influence the incidence of SBO (Table I). Direct stenting (DS) was performed in 29 patients, whereas conventional stenting (CS) with balloon predilation was performed in 51 patients (2 SBO in the DS group, 9 SBO in the CS group). The incidence of SBO in the CS group (17.6% vs 6.9%) compared with that of the DS group was higher without reaching significance. The maximum postinterventional elevation of CK and troponin I did not show a significant deviation among patients with and without acute SBO (CK 1151 F 1230 U/I vs 1263 F 2066 U/I, troponin I 30.1 F 28.9 Ag/L vs 75.4 F 127.8 Ag/L).

Clinical outcome After 230 F 167 days, angiographic follow-up could be performed in 56 of the 80 patients (70%). Clinical followup was available to all patients.

Ten patients with inhospital SBO (11 side branches). Two patients developed cardiogenic shock and died and one patient underwent coronary artery bypass surgery for treatment of postinfarct angina in the presence of left main disease, resulting in a rate of inhospital MACEs of 30%. During long-term follow-up, only one additional MACE (repeat PCI for in-stent restenosis) was encountered. Six of the other 8 occluded side branches showed late reperfusion and 2 side branches remained occluded. Seventy patients without inhospital SBO (80 side branches). Five patients died inhospital (3 of them developed cardiogenic shock, 1 patient had sepsis and another 1 died because of severe respiratory insufficiency caused by chronic obstructive lung disease) and 2 patients presented myocardial reinfarction. Three patients underwent bypass surgery for coronary 3-vessel disease (inhospital MACE rate 14%). At long-term followup, 1 sudden cardiac death and 6 major nonfatal adverse cardiac events (repeat PCI of the target lesion) were encountered. Only 2 additional side branches developed an occlusion during long-term follow-up, both occurring in patients presenting with repeat myocardial infarction (Table VI).

Discussion In patients presenting with STEMI, coronary stent implantation has been demonstrated to reduce the risk of adverse events. In lesions containing a side branch, stenting has been understood as a potential source of acute complications.1,2,5 -7,9,10,15 Previous studies focused on SBO in patients undergoing elective stent implantation. This is the first published experience investigating SBO in patients presenting with STEMI. In this study, the presence of a stent-covered side branch was a frequent morphology (29%), but only 10.9% of these side branches were occluded after stenting. Concerning elective stent implantation, other authors5,7 - 11,16,17 found an SBO rate that was in a range of 7% to 19%. We found that side branches with an ostium stenosis and an RLD V1.4 mm had the highest risk for acute occlusion. One of the most extensive studies regarding SBO (182 lesions with 224 side branches, occlusion rate 19%) was published by Aliabadi et al10 in 1997. According to this study, a preexisting ostium stenosis of the side branch was found to be a significant predictor for SBO. In other studies,5,7-11,16,17 SBO was significantly correlated with high-pressure postdilation of first-generation stents (Palmaz-Schatz and Gianturco-Roubin). This study, however, is focused on tubular stents such as JO-flex stents and AVE stents, which do not necessarily require the use of highpressure postdilation. The comparable rate of SBO gives reason to assume that SBO is less dependent on stent design or clinical presentation (acute coronary syn-

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dromes, stable angina, coronary risk factors) but primarily on the nature of a side branch. Patients with and without SBO had comparable characteristics of reperfusion therapy (time to reperfusion, door-to-balloon time, frequency of rescue PCI) and presented no significant differences regarding the occurrence of MACEs. Nevertheless, the small sample size precludes further clinical interpretations of these findings. In this study, no drug-eluting stents were used. Considering the results of Tanabe et al,18 who found no significant differences in the incidence of both acute occlusion (10% vs 7%) and late reperfusion (92% vs 67%) of side branches spanned by sirolimus-eluting versus bare metal stents, it seems unlikely that implantation of drug-eluting stents in STEMI would notably change the fate of covered side branches. The precise mechanisms that determine the flow into a side branch after stent implantation have still not been sufficiently addressed yet. It seems plausible, however, that coronary spasms and the so-called snow-plow effect (dilated ruptured plaque or thrombus that protrudes into the side branch) are the 2 major determinants of acute SBO. On one hand, animal experiments in which stents were implanted in healthy coronary arteries19 show no reduction of blood flow into the side branch, thus suggesting that acute SBO in patients with STEMI is primarily caused by displacement of the plaque or thrombus. On the other hand, a high rate of spontaneous reperfusion of initially occluded side branches represents an argument for the influence of coronary spasm or resolved thrombus on the pathogenesis of acute SBO.11

Clinical implications In patients presenting with STEMI, the origin of a side branch from a target lesion is a frequently (29%) observed morphology with a low incidence of acute SBO (11%). The strongest predictors for SBO were an RLD V1.4 mm and an ostium stenosis. In this study, the technique of stent implantation (DS or CS) had no impact on the incidence of SBO.

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