STOPAMI 1 & 2

Predictive Factors and Impact of No-Reflow After Primary Percutaneous Coronary Intervention in

Patients with Acute Myocardial Infarction

Gjin Ndrepepa, Klaus Tiroch, Dritan Keta, Massimiliano Fusaro, Melchior Seyfarth, Jürgen Pache, Julinda Mehilli,

Albert Schömig, Adnan KastratiDeutsches Herzzentrum München, Technische Universität, Munich, Germany

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STOPAMI 1 & 2Objectives of the Study

• The Relationship Between No-reflow and Myocardial Salvage Quantified by Scintigraphic Studies Before and after Primary PCI

• Predictive Factors of No-reflow after Primary PCI

• The Persistence or Resolution of No-reflow in the 6-month Angiography

• The Impact of No-reflow on the Left Ventricular Function at 6 Months and One-year Mortality

2

STOPAMI 1 & 2Methods

Baseline Tc-sestamibi Scintigraphy

Primary Percutaneous Coronary Intervention (PCI)

Tc-sestamibi Scintigraphy 7-14 Days After PCI

6-Month Coronary Angiography

One-year Follow-up

1140 Patients with Acute ST-Segment Elevation Myocardial Infarction (STEMI)

3

STOPAMI 1 & 2

Diagnosis of No-reflow and Outcomes

Diagnosis: 1. Angiographic Evidence of Re-opening of Occluded

Coronary Artery with no Evidence of Flow-limiting Residual Stenosis.

2. Angiographic Documentation of TIMI Flow Grade ≤ 2, at Least 10 Minutes after the End of PCI Procedure

Outcomes:Primary Outcome: One-year MortalitySecondary Outcomes:

- Amount of Myocardial Salvage- Predictive factors of No-reflow- Left Ventricular Ejection

Fraction at 6 Months after Primary PCI 4

STOPAMI 1 & 2Scintigraphic Parameters

• Initial Area at Risk: Perfusion Defect in the Baseline Scintigraphy (% of the Left Ventricle)

• Infarct Size: Perfusion Defect in the 7-14 Days Scintigraphy (% of the Left Ventricle)

• Absolute Salvage: Initial Area at Risk Minus Infarct Size (% of the Left Ventricle)

• Salvage index: Initial Area at Risk Minus Infarct Size Divided by Initial Area at Risk (Proportion of Salvaged Initial Area at Risk).

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STOPAMI 1 & 2Differences in Baseline Characteristics

Variable No-reflow (n =108)

Reflow (n =1032)

P value

Age (years) 65.8 [58.1; 74.9] 61.4 [52.2; 71.3] 0.001 Current smoker 33 (30.6) 418 (40.5) 0.044 Previous myocardial infarction 20 (18.5) 121 (11.7) 0.041 Killip Class 0.019 1 68 (63.0) 732 (70.9) 2 21 (19.4) 211 (20.5) 3 7 (6.5) 26 (2.5) 4 12 (11.1) 63 (6.1) Creatine kinase MB (U/L) 106.0 [47.0; 187.0] 76.0 [37.0; 156.0] 0.049 Serum creatinine (mg/dl) 1.1 [1.0; 1.4] 1.0 [0.9; 1.2] <0.001 C-reactive protein (mg/L) 14.4 [5.0; 29.4] 6.4 [0.0; 15.0] <0.001 Time-to-treatment interval (h) 10.7 [4.2; 25.6] 6.5 [2.7; 17.3] 0.001 Data are Median [25th; 75th percentiles] or number of patients (%)

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STOPAMI 1 & 2Angiographic Data

Variable No-reflow

(n =108) Reflow

(n =1032) P value

Left ventricular ejection fraction (%) 48.0 [32.8; 56.9] 50.0 [42.0; 58.0] 0.028 Number of narrowed coronary arteries

0.57

1 39 (36.1) 364 (35.3) 2 29 (26.9) 325 (31.5) 3 40 (37.0) 343 (33.2) Pre-intervention TIMI flow grade <0.001 0 90 (83.3) 564 (54.6) 1 5 (4.6) 109 (10.6) 2 10 (9.3) 189 (18.3) 3 3 (2.8) 170 (16.5) Vessel size (mm) 3.02 [2.65; 3.34] 2.93 [2.58; 3.25] 0.28 Type of intervention 0.96 Stenting 88 (81.5) 843 (81.7) Balloon angioplasty 20 (18.5) 189 (18.3) Pre-procedural abciximab therapy 84 (77.8) 800 (77.5) 0.95

Data are median [25th; 75th percentiles] or number of patients (%) 7

STOPAMI 1 & 2Scintigraphic Data

Variable No-reflow(n =108)

Reflow(n =1032)

P value

Initial Area at Risk (% of LV) 26.0 [18.5; 52.5]

24.0 [14.0; 40.0]

0.008

Infarct Size at 7-14 days (% of LV) 18.9 [10.3; 33.8]

9.1 [3.0; 20.9]

<0.001

Absolute Salvage (% of LV) 9.8 [5.3; 16.3]

12.0 [5.0; 21.0]

0.04

Salvage Index 0.34 [0.15; 0.49]

0.55 [0.29; 0.81]

<0.001

Data Are Median [Interquartile Range]

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STOPAMI 1 & 2

Salvage Index

0

10

20

30

40

50

60

0

10

20

30

40

50

60

% o

f L

eft

Ven

tric

le

% o

f L

eft

Ven

tric

le

P=0.008

No-reflow Reflow

P<0.001

No-reflow Reflow

Initial Area at Risk Final Infarct Size

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STOPAMI 1 & 2

Salvage Index

0

0.2

0.4

0.6

0.8

1.0

Reflow(TIMI Grade 3)

No-reflow(TIMI Grade ≤2)

Sal

vag

e in

dex

P<0.001

Ndrepepa et al. Circ Cardiovasc Interv. 2010;3-27-33. 10

STOPAMI 1 & 2Predictors of No-reflow

Variable Unadjusted Odds Ratio

[95% Confidence Interval]

Adjusted Odds Ratio

[95% Confidence Interval]

Previous myocardial infarction

1.71 [1.02-2.88] 2.17 [1.18-3.99]

C-reactive protein (for 1mg/L increase)

1.02 [1.01-1.03] 1.02 [1.01-1.04]

Baseline TIMI flow grade (for 1 grade decrease)

1.98 [1.52-2.57] 2.02 [1.47-2.76]

Initial area at Risk (for 5% of the LV increase)

1.10 [1.04-1.16] 1.07 [1.01-1.13]

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STOPAMI 1 & 2

No-reflow (TIMI 0-2)(n =76)

Reflow (TIMI 3) (n = 867)

TIMI Flow Grade in the 6-Month Angiography

Suboptimal Flow (TIMI 0-2)(n =121)

Normal Flow (TIMI 3) (n = 822)

761 (87.8%)61 (80.3%) 106 (12.2%)15 (19.7%)

Post-primary PCI TIMI Flow Grade

Ndrepepa et al. Circ Cardiovasc Interv. 2010;3-27-33.

Time-course of TIMI Flow

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STOPAMI 1 & 2

Left ventricular Ejection Fraction at 6 Months After PCI

Reflow No-reflow

0

2

3

4

5

EF

at

6 m

onth

s P=0.005

-15

-10

0

5

15

EF

at

6 m

onth

s

Resolution of No-reflow

Persistenceof No-reflow

P=0.002

%

1

10

-5

Ndrepepa et al. Circ Cardiovasc Interv. 2010;3-27-33. 13

STOPAMI 1 & 2One-year Survival

100

70

75

80

85

90

95

0 1 2 3 4 5 6 7 8 9 10 11 12MonthsNumbers at Risk

No-reflow

Reflow

108 95 95 90 88 87 86

1032 1003 990 976 959 943 929

Pro

bab

ilit

y o

f su

rviv

al (

%)

Hazard Ratio = 3.35, 95 CI 1.97-5.69; P<0.001

Reflow (5.5%)

No-reflow (16.7%)

Ndrepepa et al. Circ Cardiovasc Interv. 2010;3-27-33. 14

STOPAMI 1 & 2Predictors of One-Year Mortality

Variable Unadjusted Hazard Ratio

[95% Confidence Interval]

Adjusted Hazard Ratio

[95% Confidence Interval] No-reflow 3.35 [1.97-5.69] 1.91 [1.11-3.30]

Age (for 10-year increase) 2.06 [1.67-2.55] 1.85 [1.49-2.28]

Diabetes 2.53 [1.58-4.04] 1.81 [1.11-2.94]

Killip class (for 1 class increase) 2.76 [2.30-3.30] 2.38 [1.97-2.88]

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STOPAMI 1 & 2Main Findings and Conclusions

• No-Reflow after Primary PCI is Associated with Considerable Reduction of the Myocardial Salvage, Worse Left Ventricular Function and Increased One-Year Mortality

• Independent Predictors of No-reflow were: - Absence of Residual Blood Flow in the Infarct-Related Artery - Large Infarct Size - Previous Myocardial Infarction - Elevated Level of C-reactive Protein

• Normalization of Blood Flow Occurs in 80% of Patients 6 Months After Primary PCI

• Resolution of Blood Flow is Associated with Significantly Better Left Ventricular Function Compared with Persistence of No-reflow 6 Months after Primary PCI

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