Differential Clinical Impact of Angio-graphic Mechanisms Underlying

Periprocedural Myocardial Infarction Af-ter Drug-Eluting Stent Implantation

Differential Clinical Impact of Angio-graphic Mechanisms Underlying

Periprocedural Myocardial Infarction Af-ter Drug-Eluting Stent Implantation

Duk-Woo Park, MD, PhD

Division of Cardiology, University of Ulsan College of MedicineHeart Institute, Asan Medical Center, Seoul, Korea

Disclosure Statement of Financial InterestDisclosure Statement of Financial Interest

• Research funds from the CardioVascular Re-search Foundation (CVRF), Seoul, Korea and a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Korea (A102065).

• No industry sponsorship

Background Background

• Periprocedural myocardial infarction (MI) is the most common complication after PCI. The inci-dence of periprocedural MI varies from 5% to 30%, which can range from a minor elevation of cardiac enzymes to a large-sized infarct.

• The detrimental effect of periprocedural MI on survival according to the levels of enzyme eleva-tion has been well documented.

Background Background

• PCI-related MI may result from angiographically recognizable complications or angiographically non-visible mechanisms.

• Limited data are available on the relative frequency and angiographic patterns of the mechanisms un-derlying periprocedural MI and whether there are substantial differences in prognostic relevance ac-cording to these angiographic mechanisms.

PurposePurpose

• Our study was to investigate the angiographic mechanisms of periprocedural MI using a core lab. and to evaluate the different effects of periprocedural MI on mortality among patients re-ceiving drug-eluting stent (DES).

• To accomplish this, we pooled and analyzed data from available RCTs or registries designed with similar methods including case report forms, defi-nitions and adjudication procedures.

DatabaseDatabase

• Databases from 10 independent, prospective clini-cal studies (8 RCT and 2 registry), in which en-rolled patients were treated with DES for stable CAD or ACS.

• All of the studies used uniform endpoint definitions, adjudication processes, and follow-up procedures.

• All databases were maintained at the Clinical Re-search Center of the Asan Medical Center, Seoul, Korea, and a convenience sample of 10 clinical studies was available in existing merged data sets.

PCI and Cardiac Enzyme MeasurementPCI and Cardiac Enzyme Measurement

• All studies of patients undergoing PCI in whom periprocedural CK-MB data and mortality data were prospectively collected.

• Blood was routinely collected for the measurement of CK an CK-MB before stenting, every 8 hours for the first 24 hours after the procedure, and daily thereafter during hospitalization.

• Routine measurement of cardiac troponin after PCI was not performed in each center due to no reimbursement of the government for troponin measurements in PCI situations.

Periprocedural MI DefinitionPeriprocedural MI Definition

• The occurrence of MI was assessed according to the universal definition of MI.

• MI related to procedure was defined as either an(1) increase in CK-MB at least 3 times the upper

limit of normal and (2) at least 50% greater than the most recent

pre-procedure concentration; for NSTEMI/STEMI patients, peak CK-MB > 1.5 x previous trough with falling or normal CK-MB.

MI Events Adjudication and ClassificationMI Events Adjudication and Classification

• All of the studies utilized the same angiographic core lab. After evaluation of baseline and postprocedural CAG, an-giographic mechanisms of MI were recorded as one of the following:

- side-branch occlusion, - slow flow or no-reflow, - distal embolization, - thrombus, - flow-limiting dissection, - disruption of collateral flow, - others, - non-identifiable mechanical causes.

Type 1 (MI d/t SB obstruction)

Type 2 (MI d/t other angiograph-iccomplications)

Type 3 (MI withoutangiographically identifiable causes

Clinical Follow-UpClinical Follow-Up

• Among studies, clinical follow-up was performed via office visit or telephone contact at 1, 6, and 12 months and then every 6 or 12 months there-after according to the study protocol.

• For validation of complete follow-up data, infor-mation about vital status was obtained from the National Population Registry of the Korea Na-tional Statistical Office with the use of a unique personal identification number.

Statistical AnalysisStatistical Analysis

• Baseline characteristics were compared among groups without periprocedural MI and with differ-ent types of periprocedural MI by ANOVA and the χ2 test.

• Survival curves for between-groups comparisons was created using the K-M method and compared by the log-rank test.

• Univariate and multivariable Cox proportional-hazards regression models were used to estimate the effect of different types of periprocedural MI on mortality with reference to non-periprocedural MI.

RESULTSRESULTS

Summary of Merged Clinical StudiesSummary of Merged Clinical Studies

Source No. Multi-center RCT

Type of Patients or Lesions Evaluated DES Used

1. ZEST 2645 O O All-comer PCI patients ZES vs. SES vs. PES

2. ZEST-AMI 328 O O STEMI ZES vs. SES vs. PES

3. LONG-DES II 500 O O Long (> or =25 mm) SES vs. PES

4. LONG-DES III 450 O O Long (> or =25 mm) EES vs. SES

5. LONG-DES IV 500 O O Long (> or =25 mm) ZES vs. SES

6. ESSENCE-DM 300 O O Diabetic patients EES vs. SES

7. DECLARE-LONG II 499 O O Long (> or =25 mm) ZES

8. REAL-LATE 1625 O O All-comer PCI patients SES, PES, ZES, EES

9. ASAN-VERIFY 3370 X X All-comer PCI patients SES, PES, ZES, EES

10. IRIS-DES 6166 O X All-comer PCI patients EES vs. SES

Total 16383

Angiographic Mechanisms of Peri-MIAngiographic Mechanisms of Peri-MI

Underlying Causes No. (%)

Type 1

Side-branch occlusions 690 (59.9)

Type 2 (other angiographic mechanisms) 223 (19.4)

Slow- or no-reflow (abrupt closure) 93 (8.1)

Distal embolization 35 (3.0)

Thrombus 43 (3.7)

Flow-limiting dissection 42 (3.6)

Disruption of collateral flow 1 (0.1)

Others 9 (0.8)

Type 3  

Non-identifiable mechanical causes 238 (20.7)

Incidence of Periprocedural MI: 7.0% (1,151 / 16,383) Incidence of Periprocedural MI: 7.0% (1,151 / 16,383)

Rel

ativ

e P

erce

nt (

%)

All Type 1 Type 2 Type 3

CK-MB ratio: 3 to <5 5 to <10 >10

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Relative Proportions of CK-MB Levels According to the Types of Angiographic Mechanisms

Relative Proportions of CK-MB Levels According to the Types of Angiographic Mechanisms

Baseline Clinical CharacteristicsBaseline Clinical Characteristics

N (%)

VariableNo MI

(N=15232)Type 1(N=690)

Type 2(N=223)

Type 3(N=238) P Value

Age ― yr 62.4±10.3 64.3±9.4 63.7±9.7 64.8±10.0 <0.001

Men 10578 (69.5) 420 (60.9) 151 (67.7) 143 (60.1) <0.001

BMI, kg/m2 24.8±3.0 24.9±3.0 24.6±2.8 24.5±3.2 0.21

Diabetes 4926 (32.3) 232 (33.6) 68 (30.5) 69 (29.0) 0.56

Hypertension 9074 (59.6) 473 (68.6) 127 (57.0) 154 (64.7) <0.001

Current smoker 4373 (28.7) 154 (22.3) 55 (24.7) 67 (28.2) 0.002

Hyperlipidemia 6930 (45.5) 357 (51.7) 129 (57.9) 108 (45.4) <0.001

Baseline Clinical CharacteristicsBaseline Clinical Characteristics

N (%)

VariableNo MI

(N=15232)Type 1(N=690)

Type 2(N=223)

Type 3(N=238) P Value

Previous MI 777 (5.1) 26 (3.8) 10 (4.5) 10 (4.2) 0.40

Previous PCI 2174 (14.3) 80 (11.6) 33 (14.8) 27 (11.3) 0.14

Previous CABG 295 (1.9) 11 (1.6) 2 (0.9) 1 (0.4) 0.25

Previous CHF 234 (1.5) 11 (1.6) 3 (1.4) 5 (2.1) 0.83

Previous stroke 907 (6.0) 47 (6.8) 14 (6.3) 22 (9.2) 0.15

PVD 227 (1.5) 13 (1.9) 6 (2.7) 4 (1.7) 0.33

Chronic lung disease 255 (1.7) 11 (1.6) 7 (3.1) 5 (2.1) 0.32

Renal insufficiency 315 (2.1) 22 (3.2) 4 (1.8) 9 (3.8) 0.07

ACS 8526 (56.0) 319 (46.2) 105 (47.1) 127 (53.4) <0.001

EF (%) 59.2±8.9 59.7±7.8 57.4±9.9 59.8±9.5 0.006

Baseline Lesion CharacteristicsBaseline Lesion Characteristics

N (%)

VariableNo MI

(N=15232)Type 1(N=690)

Type 2(N=223)

Type 3(N=238) P Value

Multivessel disease 7681 (50.4) 492 (71.3) 153 (68.6) 157 (66.0) <0.001

LAD disease 9513 (62.5) 514 (74.5) 154 (69.1) 168 (70.6) <0.001

Left main disease 843 (5.5) 80 (11.6) 21 (9.4) 23 (9.7) <0.001

Bifurcation lesion 3900 (25.6) 306 (44.4) 91 (40.8) 91 (38.2) <0.001

Long lesion (>20 mm) 10925 (71.7) 631 (91.5) 198 (88.8) 206 (86.6) <0.001

Total occlusion 2309 (15.2) 49 (7.1) 46 (20.6) 31 (13.0) <0.001

Baseline Procedural CharacteristicsBaseline Procedural Characteristics

N (%)

VariableNo MI

(N=15232)Type 1(N=690)

Type 2(N=223)

Type 3(N=238) P Value

DES subtype <0.001

Sirolimus 6886 (45.2) 304 (44.1) 106 (47.5) 98 (41.2) <0.001

Paclitaxel 1874 (12.3) 69 (10.0) 15 (6.7) 20 (8.4)

Zotarolimus 2160 (14.2) 79 (11.5) 32 (14.4) 22 (9.2)

Everolimus 3591 (23.6) 204 (29.6) 59 (26.5) 85 (35.7)

Resolute zotarolimus 473 (3.1) 30 (4.4) 8 (3.6) 11 (4.6)

Others 248 (1.6) 4 (0.6) 3 (1.4) 2 (0.8)

No. of stents 1.7±1.0 2.7±1.3 2.5±1.3 2.3±1.2 <0.001

Total stent length, mm 42.3±26.8 63.2±33.2 61.3±33.9 54.6±32.9 <0.001

Guidance of IVUS 9269 (60.9) 510 (73.9) 160 (71.8) 152 (63.9) <0.001

Use of Gp IIb/IIIa inhibitor 3668 (24.1) 121 (17.5) 66 (29.6) 48 (20.2) <0.001

Use of cilostazol 3950 (25.9) 212 (30.7) 64 (28.7) 65 (27.3) 0.03

K-M Curves According to Types of Periprocedural MI

K-M Curves According to Types of Periprocedural MI

Incidence Rates, Unadjusted and Adjusted HR for Mortal-ity, According to the Type of Periprocedural MI

Unadjusted Adjusted†

Outcome

Total No. and 2-year rate of

eventsHR

(95% CI) P HR

(95% CI) P

No Peri-MI (N=15232) 307 (2.0%) Referent Referent

Peri-MI (N=1151) 37 (3.6%) 1.76 (1.24–2.48) 0.001 1.43

(1.08–1.89) 0.01

Type 1 (N=690) 16 (2.8%) 1.27 (0.79–2.06) 0.32 1.08

(0.67–1.73) 0.77

Type 2 (N=223) 13 (6.1%) 3.06 (1.57–5.96) 0.001 2.69

(1.57–4.63) 0.0003

Type 3 (N=238) 8 (3.2%) 1.87 (1.08–3.23) 0.02 1.27

(0.94–1.72) 0.12

†Adjusted for study, age, sex, BMI, DM, HTN, smoking, hyperlipidemia, history of MI, PCI, or stroke, chronic lung disease, renal insufficiency, ACS, EF, MVD, LM disease, bifurcation, total occlusion, DES type, total number of stents, and use of Gp IIb/IIIa inhibitor.

ConclusionConclusion

• Among patients who underwent PCI with DES, periproce-

dural MI was associated with an increased risk of mortality.

• There were substantial differences in mortality depending

on the different angiographic mechanisms of periprocedu-

ral MI, showing that MI due to complicated angiographic

causes was related with increased mortality, whereas MI

due to side-branch occlusion or without identifiable angio-

graphic causes did not affect mortality.

Clinical ImplicationClinical Implication

• The 3rd definition of MI adopted a ≥5 enzyme elevations

and considered angiographic evidence of flow-limiting

complications (such as loss of SB occlusion, slow flow or

no-reflow, or embolization) as diagnostic criteria.

• However, the clinical impact of angiographic mechanisms

of periprocedural MI is still unknown.

• The overall findings of our study highlight the need for fur-

ther research to determine the diagnostic and prognostic

value of angiographic mechanisms, when defining

periprocedural MI, and to inform optimal management of

these complications.